Spring 2015 -- Granting Total Immunity by Carolina Scientific

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Carolina Scientific

sc覺ent覺fic Spring 2015 | Volume 7 | Issue 2

GRANTING TOTAL IMMUNITY improving plant immune systems to combat world hunger full story on page 24

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scıentific Mission Statement: Founded in Spring 2008, Carolina Scientific serves to educate undergraduates by focusing on the exciting innovations in science and current research that are taking place at UNCChapel Hill. Carolina Scientific strives to provide a way for students to discover and express their knowledge of new scientific advances, to encourage students to explore and report on the latest scientific research at UNC-Chapel Hill, and to educate and inform readers while promoting interest in science and research.

Letter from the Editors: Research can be messy. Experiments fail, data sets give mixed results, and researchers must go back to the drawing board. So why bother muddling through the tedium and the frustrations? Above all else, scientists want to find answers, to solve the puzzle that their research presents. This issue of Carolina Scientific is no exception. We feature biologists who are determined to identify new species in NC’s Great Smoky Mountains (page 28) and a professor who has devoted her research to understanding the effects of maternal drug abuse (page 40). Others use their research to help aspiring scientists succeed. At UNC, physics professors are modifying their teaching methods based on research in the classroom (page 36), and one physician’s team is developing a surgical simulation device to train new doctors (page 46). We hope that you join us in celebrating the unique discoveries and innovations that take place daily on UNC’s campus. Enjoy! –Erin Moore & Josh Sheetz

on the cover

As food shortages due to crop losses become an increasing health concern worldwide, Dr. Jeff Dangl’s research group is working to improve the natural ability of plants to fight pathogens. See the full story on page 24. Illustration by David Wright.

Executive Board Co-Editors-in-Chief Erin Moore Josh Sheetz Associate Editors Corey Buhay Matt Leming Parth Majmudar Design Editor Tracie Hayes Copy Editor Kimberly Hii Online Content Manager Jasmin Singh Public Outreach Chair Brian Davis Fundraising Chair Karthika Kandala Treasurer Linran Zhou Faculty Advisor Gidi Shemer, Ph.D. Contributors Staff Writers

Design Staff

Emily Batchelor Seth Bollenbecker Seth Bollenbecker Clara Lee Kennedi Briggs Aileen Ma Corey Buhay Sahana Raghunathan Rukmini Deva Ivy Somocurcio Sara Edwards Copy Staff Camille Gonzales Aly Helms Natan Holtzman Kimberly Hii Shuyan Huang William Howland Kammy Liu Katie Huber Ben Penley Sungwon Hwang Courtney Roof Matt Leming Taruni Santanam Arantxa Lopez de Juan Abad Christine Son Nathan Lunsford Julianne Yuziuk Kara Marker Avery McGuirt Illustrators Sarah Miller Maura Hartzman Ben Penley Ace Lane Sahana Raghunathan Donna Li Blake Riley Kristen Lospinoso Mai Riquier Tatihana Moreno Jonathan Smith David Wright Ivy Somocurcio Julianne Yuziuk Hope Thomson Jeffrey Young

Carolina Scientific

contents Chemistry

Physics and Technology

Natureâ&#x20AC;&#x2122;s Treasure Chest

Nanotechnology and Drug Delivery

Blink and Youâ&#x20AC;&#x2122;ll Miss It 1000 Times

The Syrup in Our Veins

Memorize Your Shapes

The Plastic Bag that Saves Lives

The Love Drug Cure

Not Quite the Iron Lung

Combating Diabetes From Within

The Gravity of Learning Physics

Photosynthetic Puzzles

Emily Batchelor

William Howland Sungwon Hwang Ben Penley Blake Riley

Nathan Lunsford Corey Buhay

Sara Edwards

Nathan Lunsford Mai Riquier

Psychology and Information Science

Hope Thomson

Biology

Google It Under Pressure

What Lies Behind the Cries

Brains Behind Psychiatric Disorder

Kimberly Hii

Peacocking

The Mysteries of Morphogenesis

Bacterial Gossip

Molecular Motors

Type A Community Service

To Feed Every Mouth

Surgical Simulation

No Fish if You Overfish

Taking Inventory of Life

Camille Gonzales Katie Huber

Aly Helms

Kennedi Briggs

Medicine

Sarah Miller

Sahana Raghunathan Ivy Somocurcio

Rukmini Deva Jeffrey Young

Special Features

Seth Bollenbecker

Arantxa Lopez de Juan Abad

carolina_scientific@unc.edu carolinascientific.org facebook.com/CarolinaScientific @uncsci

My Science Major is Easy

Do It With Campus Makerspaces

A More Diverse Tomorrow

Enhancing an Education

Avery McGuirt Matt Leming

Jonathan Smith Kara Marker

chemistry

Dr. Bo Li’s lab studies natural products of soil bacteria, such as the one shown here, to combat the growing problem of antibiotic resistance. Photo by National Institute of Health. CC BY-SA 3.0

Nature’s Treasure Chest Natural products may offer solution to antibiotic-resistant bacteria BY EMILY BATCHELOR

he solution to one of the biggest health threats in the world may be just under your feet. Microscopic bacteria in the soil could harbor the solution to the rapidly growing problem of antibiotic resistance. The development of antibiotics in the early 20th century has led to more effective treatment for infectious diseases.1 However, the microbes causing these diseases are becoming increasingly resistant to current antibiotics, and scientists all over the world are searching for ways to combat this potentially catastrophic phenomenon.1 Among them is Dr. Bo Li, an assistant professor in the department of chemistry at UNCChapel Hill, who is currently investigating the natural products of soil bacteria as prospective next-generation antibiotics. Many of the drugs currently used in clinics come from nature. For years, molecules secreted by plants, bacteria and fungi have served a wide range of medicinal purposes. Furthermore, because of recent advances in genome sequencing, scientists now know that there are countless molecules yet to be discovered. It is estimated that less than one percent of these compounds have been identified and studied by scientists. “A major goal of our lab is to develop technologies to be able to mine this treasure trove in nature to find these new

molecules and apply them in a way that would be useful to human health,” Dr. Li said.2 Natural products, also known as secondary metabolites, are small molecules made by living organisms. Natural products are not typically essential for the growth, development or reproduction of an organism. Dr. Bo Li They do, however, provide defensive mechanisms, facilitate reproductive processes, and empower organisms to survive interspecies competition.3 “For example, if you have two bacteria that live in the soil and they are competing for resources, they can secrete these compounds and try to inhibit the other bacterium,” Dr. Li said.2 Her lab primarily focuses on these natural products of soil bacteria. It is because of these properties that natural products have been so useful in medicine and have played a pivotal role in the development of successful antibiotics throughout the last century. “Natural products can inhibit cellular targets,

Carolina Scientific and we can take advantage of that and use it to treat diseases,” Dr. Li said.2 As antibiotic resistance rises, medicinal chemists have looked again to natural products, as many of these compounds still remain underexplored due to a lack of understanding of their basic mechanisms.4 Dr. Li’s research program aims to learn more about these natural products through a process called genome mining (Figure 1). “To put it in a nutshell, natural products are made by proteins, and proteins are encoded by genes, which are all in the genome,” Dr. Li said.2 Through the use of bioinformatics tools, scientists are able to follow the intricate paths that lead to the syntheses of these compounds, starting at the genes, going to proteins and then to the molecules. Dr. Li and her team are able to mine bacterial genomes for genes that are likely to produce natural products and subsequently connect those genes to the chemicals they are making. Dr. Li’s lab has made headway in understanding one class of antibiotics and how it is made. Dithiolopyrrolones, or DTPs, are a structurally and electronically unique class of antibiotics that have yet to be used therapeutically. DTPs are broad-spectrum antibiotics, which means that they are effective against a wide variety of bacterial pathogens. Despite this appealing biological quality, DTPs are not currently used in clinics because of their toxicity.4 The Li Group was able to use genome mining to identify the genes involved in making these antibiotics and has started to decipher the chemistry involved in their syntheses and mechanisms of action.5, 6, 7 One specific antibiotic they have looked at in the class of DTPs is called holomycin. Members of the Li group are using their chemical knowledge to make new variants of holomycin that improve its potency against difficult-to-eliminate bacteria. Furthermore, they recently identified a novel mechanism in nature that links part of holomycin to another FDA-approved antibiotic, pseudomonic acid, creating a hybrid molecule with increased potency against methicillin-resistant Staphylococcus aureus (MRSA).8 “A major goal of our lab is However, they inihad trouble to develop technologies tially with the isolation to be able to mine this of holomycin. Six months of using the treasure trove in nature reported conditions to find new molecules for the soil bacteand apply them in a way rium that produces holomycin yielded that would be useful to no results. Dr. Li then human health.” decided to come up with other ways to -Dr. Bo Li get the bacterium to produce the compound. When they changed to a solid medium, the bacteria began to grow differently. In a petri dish where the bacteria were growing, Dr. Li noticed a circle of yellow compound, which was tested and confirmed to be holomycin. “I thought — wow, could this actually be holomycin?” she recalled.2 Successful isolation of holomycin also enabled further research by the Li group on this antibiotic. “The whole path of research is about overcoming obstacles,” Dr. Li said.2

chemistry

Figure 1. A bacterial genome atlas. Dr. Li and her team are able to mine bacterial genomes for genes that are likely to produce natural products. By studying the chemistry behind how these bioactive molecules are made, the Li group was able to gain a deep knowledge of biology at the molecular level. “We can actually connect something kind of abstract, which is chemistry, to something that is applicable, like a drug, something directly related to human health and biology,” Dr. Li said.2 There is great importance to be found in Dr. Li’s work. From a scientific perspective, bridging the gap between chemistry and biology is an opportunity for new and exciting discoveries. From a health perspective, the world needs new antibiotics to replace the outdated ones that can no longer treat many infectious bacteria. Dr. Li’s dream is for these naturally occurring molecules, which have shown superior properties as medicine, to be an area for next-generation antibiotics. Her research stands at the interface of chemistry and biology, working to combat the insurgence of multidrug-resistant bacteria that pose a tremendous threat to the health of the entire world.

References

1. Antibiotic/Antimicrobial Resistance. http://www.cdc. gov/drugresistance/ (accessed February 7th, 2015). 2. Interview with Bo Li, Ph.D. 02/03/15. 3. Vaishnav, P.; Demain, A.L. Biotechnol. Adv. 2011, 29(2), 223–229. 4. Li, B.; Wever, W.J.; Walsh, C.T.; Bowers, A.A. Nat. Prod. Rep. 2014, 31, 905–923. 5. Li, B.; Walsh, C.T. PNAS. 2010, 107(46), 19731–19735. 6. Li, B.; Walsh, C.T. Biochemistry. 2011, 50, 4615–4622. 7. Li, B.; Forseth, R.R.; Bowers, A.A.; Schroeder, F.C.; Walsh, C.T. ChemBioChem. 2012, 13(17), 2521–2526. 8. Dunn, Z.; Wever, W. J.; Economou, N. J.; Bowers, A. A.; Li, B. Angew. Chem. Int. Ed. 2015, 54, 1–6.

chemistry

BLINK and you’ll miss it 1000 times

products, such as plastics, but also for life itself in the form of enzymes, nature’s catalysts. During her time as a graduate student at the California Institute of Technology, Dr. Dempsey conducted kinetic studies that helped to determine how a certain catalyst could be brought closer to real-world use. She was investigating a class of compounds referred to as cobaloximes.2 These compounds seemed promising for their ability to catalyze the production of hydrogen gas, a desirable future energy source that produces only water when burned. Dr. Dempsey’s group had created a fairly effective catalyst that worked when floating freely in solution, but there

BY WILLIAM HOWLAND

o create a machine, a designer needs to understand how all of the components fit together. In the case of a machine like a car, these components are things like gears, pistons, and belts. But for a chemical “machine,” these components are on the scale of billionths of meters and often carry out their tasks Dr. Jillian Dempsey in a thousandth the time it takes to blink. Understanding how such components work is an enormous challenge, but the rewards are far-reaching, from synthesis of disease-treating compounds to storage of light energy in the chemical bonds of sugar (Figure 1). If scientists could match the fantastic chemical abilities of living organisms, they could revolutionize fields as disparate as medicine and energy. Professor Jillian Dempsey, the principal investigator of a three-year-old research group in UNC-Chapel Hill’s department of chemistry, focuses much of her work on this challenge. She investigates the kinetics of chemical reactions — how quickly they occur under various conditions. These studies help to improve understanding of how reactions work. “One important piece of information that reaction kinetics provides us is a mechanistic picture,” Dr. Dempsey said.1 In other words, studying kinetics allows us to understand what path a reaction has taken to get from Point A to Point B (or, more appropriately, from Chemical A to Chemical B). Using the mechanistic roadmap provided by the kinetics study, chemists can determine how to help the reaction along and how to make the reaction happen more rapidly or at lower temperatures. They can even make educated guesses at what other chemicals might be able to react in a similar way. These findings can potentially allow for the creation of new or more inexpensive compounds that may prove useful as materials or pharmaceuticals. Mechanistic information is also important in the design of catalysts. A catalyst is a chemical “machine” that helps chemical reactions to occur more quickly and with less heat. These machines have a profound impact on daily life as they are crucial for not only the production of many consumer

Figure 1. The microscopic machinery of photosynthesis is anything but simple. This complex of proteins is only a part of the sugar-manufacturing factory plants rely on for sustenance. Figure by Wiki-Freund-5, CC-BY-SA 3.0

If scientists could match the fantastic chemical abilities of living organisms, they could revolutionize fields as disparate as medicine and energy.

Figure 2. The Dempsey Group uses this high-precision instrument to study kinetic events that occur in millionths of a second. Photo by William Howland.

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chemistry

velopment of more efficient ways to store energy in the form of chemical fuels. Ideally, the energy stored in the fuel would come from a renewable source such as the sun, so Dr. Dempsey’s specific focus is electron transfer driven by light. When designing a complete chemical system for light, several components are necessary, and how these components should be linked together is no simple question. “We might have one molecule or material that absorbs light and another molecule or material that carries out the chemical catalysis reaction that makes the fuel,” Dr. Dempsey said. “We look at how, depending on how we connect those two parts, we can affect the device performance.” So, in a sense, Dr. Dempsey is investigating the “drive shaft” of the fuel creation device.1 In her investigation of light-driven electron transfers, Dr. Dempsey uses a technique known as transient absorption spectroscopy. In this technique, chemical reactions are initiated by short bursts of intense laser light that give the chemicals the energy “kick” they need to react (Figure 2). In Dr. Dempsey’s laser setup, these bursts occur 10 times per second and last seven billionths of a second each. After each pulse, the instrument records the color of the solution as the reactants change into products (Figure 3). Because these experiments are designed to have products, intermediates and reactants with distinct colors, this information can be used to determine how quickly the reactants are used up and how quickly the products form, and even to identify additional temporary compounds that are between the starting and ending compounds. There are several other types of experiments commonly used to monitor kinetics, but Dr. Dempsey has been drawn to this laser-based technique since she was an undergraduate at MIT. “I actually really liked the tools,” she said, “I really liked the idea of working with optics; that’s kind of what motivated me. So I found the hammer and then I found the nail!” From Dr. Dempsey’s perspective, “There is no doubt that we will, as a community, be able to turn sunlight into fuels at some point in our lifetime.” With this ambition coupled to the ever-growing understanding of electron transfer processes that accumulates through the study of their kinetics, this world-changing discovery is anything but unattainable.

“There is no doubt that we will, as a community, be able to turn sunlight into fuels at some point in our lifetime.”

Figure 3. Data gathered with the laser system takes the form of a series of curves showing which colors (wavelengths) of light are absorbed by the solution at different points in time. Image courtesy of Dr. Dempsey. were concerns as to whether or not the catalyst would still function once attached to a solid substrate. Catalysts are often expensive, so it is preferable for practical applications that they be reusable. This is most easily achieved by attaching the catalyst to a solid material that is easily recovered from the reaction vessel. “There was a lot of question as to whether or not this catalyst acted on its own or worked tag-team with another catalyst,” Dr. Dempsey said.1 If the latter were the case, tying the catalyst down would stop it from working, because if immobilized on a solid, it would never be able to hit another catalyst. When not tied down, the catalyst was free to “swim around” in solution until it hit another catalyst and completed the reaction. Attaching a catalyst to a solid substrate is no trivial task, so it was desirable to use kinetics to determine whether or not the anchored catalyst would work at all. In the end, the kinetics data indicated that the catalyst was in fact functioning on its own, giving a green light to the plans to attach the catalyst to a surface. This scenario is a perfect example of how mechanistic information — gleaned from the investigation of kinetics — can be a valuable guide in the development of catalytic systems. Dr. Dempsey currently investigates the transfer of subatomic particles called electrons in reactions that occur in less than a tenth of a millisecond.3 Electrons can be thought of as the currency of chemical energy. In photosynthesis, the addition of electrons to carbon dioxide is essential for its conversion into sugar, a substance that contains large amounts of stored energy. Conversely, the driving force behind energyreleasing processes that power living cells comes from oxygen taking electrons from fuels like sugar. Understanding how electrons move in a chemical system is thus central to the de-

References

1. Interview with Jillian Dempsey, Ph.D. 02/05/15. 2. Dempsey, J.L.; Brunschwig, B.S.; Winkler, J.R.; Gray, H.B. Acc. Chem. Res. 2009, 42, 1995–2004. 3. Eisenhart, T.T.; Dempsey, J.L. J. Am. Chem. Soc. 2014, 136(35), 12221–12224.

chemistry

memorize your

How Certain Materials May Be Better Than You at Memorizing Shapes

By Sungwon Hwang

plastic arm grabs onto an object, picks it up, moves the object and places it down. Nothing special, right? Here is the catch: This particular device would not require any electrical or mechanical power to move. Instead, it would rely on its memory. Dr. Sergei Sheiko and his research group in the chemistry department at UNC-Chapel Hill are studying these materials that are said to have “shape memory.”1 Shape memory is the ability of a material to change back in to a specific shape that has been determined in advance. Simple shape memory basically works by manually changing the shape of a material and freezing it. When the temperature is raised, the material will return to its original shape. This process is usually irreversible, meaning that the material loses its shape memory once

heated and, therefore, cannot be used again.2 Dr. Sheiko began to study shape memory about three years ago, curious if certain materials could shapeshift reversibly. His group currently studies shape memory in polymers, large molecules made up of repeating subunits called monomers. Polymers can be thought of as long chains of paperclips, with a single paperclip being the monomer. Elastomers, highly flexible polymers such as rubber, were the primary subject in Dr. Sheiko’s research. By studying elastomers and their shape memory, Dr. Sheiko’s group has found two different kinds of reversible shape memory (RSM): two-way and one-way.2 In two-way RSM, the elastomer is able to “remember” two shapes and switch between them at different temperatures.2 For instance, a linear elasto-

5° C

34° C

mer can be given a coil shape in a low-temperature environment of 5 degrees Celsius. If the temperature is then raised to 38 degrees Celsius, it will revert back to its original linear Dr. Sergei Sheiko shape. When the temperature is lowered again to 5 degrees Celsius, the material will change back to a coil again. This two-way RSM is very repeatable, maintaining shape memory even after many sets of cooling and heating. Since 38 degrees Celsius is very close to the physiological range of temperatures, there is exciting potential for two-way RSM materials to be incorporated inside the body. While two-way RSM can be re-

60° C

Figure 1. An example of rod-coil-rod one-way reversible shape memory. A coiled elastomer becomes a linear rod when cooled to 5°C. It reverts back to its original coil shape after the temperature is raised, but when the temperature is raised even higher to 60°C, it uncoils into a rod shape. Image courtesy of Dr. Sheiko.

chemistry

Carolina Scientific peated multiple times, one-way RSM can happen only once. Just as in twoway RSM, the elastomers are given a specific shape and are cooled to 5 degrees Celsius.2 They revert back to their original shape after the temperature is raised, but when the temperature is raised even higher to 60 degrees Celsius, the elastomers change back to the first shape. For example, an elastomer that is put into a coil shape at 5 degrees Celsius would uncoil into a rod shape when heated and would revert to the coil when heated even further. Although one-way RSM can only be used once, it has a distinct advantage over two-way RSM; in one-way RSM, both of the resulting shapes are stable at room temperature since only heating is needed to change the shapes, while cooling must also be incorporated in two-way RSM. Reversible shape memory has many appealing qualities that heighten its potential for exciting applications. “Shape memory can memorize very complex shapes — coils, stars, squares, circles and origami-type shapes,” Dr. Sheiko says.1 This sets shape memory apart from “shape-changing” materials, which simply expand at high temperatures and shrink back at lower temperatures. The specificity of shape memory allows for more control and makes the

Shape memory is distinct from “shape-changing” materials, which expand at high temperatures and shrink back at lower temperatures. technology useful in various applications. Dr. Sheiko also says that RSM is universal and works for an assortment of materials including liquid crystals, foams and gels.1 The materials are usually extremely durable, and their sizes can range from nanometers to macroscopic lengths. Aside from temperature, RSM can also work in response to light and sound. There are many potential applications of RSM that come to Dr. Sheiko’s mind. Materials with RSM may be used in surgical techniques such as stents,

Figure 2. (Top left) Cooled polymers soften in higher temperatures (top right) and can form new shapes. (Bottom) An example of an origami-shaped two-way reversible shape memory. It can be used as a claw that will grip onto objects. Images courtesy of Dr. Sheiko. which are devices that expand blood vessels. The technology can also have applications in space exploration. Dr. Sheiko gives the example of an umbrella-shaped antenna that can be tightly packaged and sent into space, where it can unpack itself into a functional shape and revert to the condensed form.1 He also reveals that the Department of Defense is interested in these shape-shifting materials for potential spy devices. One can imagine a thin paper-like material that is slid under a door and quickly changes into a functional spy device for monitoring and sensing. Despite the exciting potential of reversible shape memory in various applications, Dr. Sheiko emphasizes that the main goal of his research is not to develop new technology with RSM, but rather to understand how the process works and what chemical relationships are relevant.1 “The discovery [of reversible shape-shifting materials] itself hap-

pened more or less instantaneously,” Dr. Sheiko says, “but the [mechanism behind] this, we still do not understand.”1 Currently, the main focus of his research is determining the chemical relationships that make shape memory possible and establishing universal correlations between a material’s chemical structure and its macroscopic shape.

References

1. Interview with Sergei Sheiko, Ph.D. 01/30/15. 2. Zhou, J.; Turner, S.A.; Brosnan, S.M.; Li, Q.; Carrillo, J.Y.; Nykypanchuk, D.; Gang, O.; Ashby, V.S.; Dobrynin, A.; Sheiko, S.S. Macromolecules. 2014, 47(5), 1768-1776.

chemistry

Illustration by Ace Lane

the LOVE DRUG cure

oxytocin offers potential treatment for social anxiety BY BEN PENLEY

he cure for social anxiety disorders might be in Ecstasy and childbirth. That is, the hormone oxytocin — commonly referred to as the “love hormone” — could be the key. Dr. Michael Jarstfer and his lab in collaboration with Drs. Sheryl Moy, Ph.D. and Cort Pederson, MD (UNC, Psychiatry) research the effects of oxytocin on social motivation and how small molecule derivatives might be used to treat diseases like autism. “With relation to social deficits, oxytocin is considered a potentially useful therapeutic,” said Dr. Jarstfer.1 To understand its potential, Dr. Jarstfer and his team plan to investigate the mechanism of oxytocin’s effects. The most extreme example comes with an extreme drug: Ecstasy. After Ecstasy is consumed, oxytocin is released. Ecstasy would not be the social drug it is without the release of oxytocin,

because it is oxytocin that increases trust, sexual arousal and other social aptitudes. Oxytocin is also known to mediate the more sober and natural function of childbirth. It binds to receptors on the uterine wall and signals an increase in calcium buildup. The calcium buildup causes the muscles to contract and ultimately induces labor. Once the child is born, oxytocin assumes a new role as the hormone responsible for mother-child bonding.

Dr. Michael Jarstfer

chemistry

Carolina Scientific In order to discover potentially useful pharmaceuticals in the treatment of social anxiety disorders, it is necessary to quantify the drugs’ effects on test subjects. Therefore, a model system, using mice, is necessary to gauge sociability. The assay involves placing a subject mouse in the middle of a threeroomed chamber.2 One room holds a stranger mouse. The other room is empty. The subject mouse, then, is allowed to wander for ten minutes, freely choosing where to spend its time. If the subject mouse spends more time with the stranger, it is deemed “social.” If the subject mouse instead favors the empty room, it has a social defect and will be subjected to further experimentation. The mice with social ineptitudes are given an injection of oxytocin. The immediate results show that while the social skills of the mice do not improve, their social anxiety is reduced. For example, if the mouse is placed in a cage with a bed of marbles, it will bury fewer of the marbles after the injection. In addition to reduced marble burying, oxytocin treatment can also reduce other repetitive behavior. These results may indicate a lessened sense of anxiety, as the mice no lon-

Figure 1. The setup of the three-roomed chamber task. One room holds a stranger mouse and the other room is empty. The subject mouse is then allowed to wander for ten minutes, freely choosing where to spend its time. If the subject mouse spends more time with the stranger, it is deemed “social.” Image courtesy of Dr. Jarstfer.

Ecstasy would not be the social drug it is without the release of oxytocin, because it is oxytocin that increases trust, sexual arousal and other social aptitudes. ger worry about the unknown objects (i.e. marbles) or other sources of stress that lead to repetitive behaviors. If, however, the mice are given a sub-chronic treatment regime, or periodic injections over the course of eight days, their social interactions improve. Moreover, the ability of oxytocin to reverse social deficits in mouse models appears persistent, meaning that long after treatment, mice retain sociability. The mouse model, however, might not be completely consistent with humans. Although some of oxytocin’s effects are known, it is not clear how it works on the molecular level. On the surface, the induction of labor, marble burying, and social bonding seem unrelated. To understand its molecular basis and thus its phenotypic effects, small molecules derived from oxytocin are developed in Dr. Jarstfer’s lab. The development of these small molecules is the tool used to gain insight into how oxytocin works. “We found that the oxytocin receptor can signal a cell to respond in different ways — through different pathways,” said Dr. Jarstfer.1 The synthesized small molecules target one of two pathways that oxytocin can follow once active. One pathway, the Gq pathway, appears to be responsible for a reduction in marble burying and promoting uterine contractions but is not related to the offset of social deficits. Another pathway, the beta-arrestin pathway, may be the key to reversing social deficits but is not effective in reducing marble burying. If this model is accurate, then for the purposes of treating social

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Figure 2. In the three-roomed chamber task, the amount of time spent with the stranger mouse increases after periodic oxytocin injection. Image courtesy of Dr. Jarstfer. impairments like autism, it will be important to develop molecules that activate the beta-arrestin pathway. Dr. Jarstfer and his lab are working to discover such stable drugs. By targeting a specific pathway, scientists predict that side effects will be minimized, and an effective treatment for social anxiety disorders will hopefully become a reality.

References

1. Interview with Michael Jarstfer, Ph.D. 02/12/15. 2. Teng, B.L.; Nonneman, R.J.; Agster, K.L.; Nikolova, V.D.; Davis, T.T.; Riddick, N.V.; Baker, L.K.; Pedersen, C.A.; Jarstfer, M.B.; Moy, S.S. Neuropharmacology 2013, 72, 187–196.

chemistry

Transverse section of blood vessels. Image by Franck Genten, CC-BY-2.0.

COMBATING DIABETES FROM WITHIN BY BLAKE RILEY

he Centers for Disease Control and Prevention (CDC) estimate that 29.1 million Americans, or 9.3 percent of the population, suffer from diabetes. The disease, which is characterized by an excess amount of glucose in the bloodstream, is currently undiagnosed in about 8.1 million people.1 Those who suffer from diabetes commonly monitor their blood glucose by pricking their finger two to eight times a day in order to obtain a blood sample. A meter then analyzes the blood sample for its glucose content and logs the results.2 This method of finger

pricking and blood glucose monitoring is monotonous, time-consuming and often unpleasant. Dr. Mark Schoenfisch, professor of chemistry at UNC-Chapel Hill, is working with his research group to develop a solution to this problem. To improve blood glucose monitoring, Dr. Schoenfisch is currently developing glucose sensors that can be inserted into a patientâ&#x20AC;&#x2122;s subcutaneous tissue (which is the third layer of the skin tissue and contains blood vessels) to analyze glucose levels from within the body. Embedded in the sensor is the enzyme glucose oxidase, which cata-

lyzes a reaction to form hydrogen peroxide in the presence of glucose and oxygen. The sensors electrochemically detect the amount of hydrogen peroxide pres- Dr. Mark Schoenfisch ent as an indirect measure of glucose in the blood. According to Dr. Schoenfisch, a couple of glucose biosensors exist on

chemistry

Carolina Scientific the market today. However, they are only approved by the Food and Drug Administration for five to seven days. “Their analytical performance is poor. After a five- to seven-day period they stop working reliably, and it’s because of the body’s immune response to the implant, much like a splinter,” Dr. Schoenfisch said. “There’s inflammation and encapsulation of this foreign body. The encapsulation makes for poor performance of the glucose sensor because the blood glucose of the interstitial fluid [fluid that surrounds cells] cannot reach the sensor.”3 Dr. Schoenfisch and his research group want to address this foreignbody response to the sensor and in turn enhance its biocompatibility. To accomplish this, the group is developing glucose sensors with membranes that release nitric oxide (NO). NO is thought to help prevent the body’s inflammation response to the sensor by promoting revascularization, inhibiting platelet aggregation, preventing the formation of a capsule around the sensor and killing bacteria within the proximity of the sensor. Studies have shown that thinner capsules and greater blood vessels form around implanted sensors with NOreleasing membranes, suggesting that the release of NO improves the sensors’ biocompatibility.4 The membrane that surrounds the embedded glucose sensor is com-

Figure 2. A diagram of the skin tissue layers. The blood glucose sensors are inserted into the subcutaneous tissue layer, which contains the blood vessels. Image by Madhero88, CC-BY-SA-3.0.

Figure 1. (Left) The expected foreign-body encapsulation response to an implanted glucose sensor. (Right) When NO is released around the sensor, no encapsulation occurs. Image courtesy of the Schoenfish Research Group. posed of nanoparticles, which help to facilitate the storage and release of the NO particles. This release may be triggered by something as simple as water or heat.4 According to Dr. Schoenfisch,

Dr. Schoenfisch and his research group want to address this foreign-body response to the sensor and in turn enhance its biocompatibility. however, nanoparticles are generally difficult to synthesize. “You’re working with something small. To get homogenous nanoparticles, both in composition and size, you really have to fine-tune the chemistry. It’s been a several-year process to optimize these nanoparticles.”3 The results of Dr. Schoenfisch’s research are promising. In animal models, the glucose sensors have successfully released NO and were able to monitor blood glucose levels for up to 10 days, an improvement upon the five to seven days that existing sensors are able to monitor. Still, as with any form of scientific research, surprising results and challenges present themselves. For instance, particles other than NO may leach from the sensor membrane. “Depending on the formulation that you use, sometimes you observe particle leaching. Then you have particles and NO coming out, and the particles are not what you want being released in the tissue,”3 Dr. Schoenfisch said.

As Dr. Schoenfisch moves forward with his research, he is interested in implanting and testing NO-releasing blood glucose sensors in diabetic animals. “The physiology associated with diabetes is much different than the physiology associated with an organism without diabetes. We want to understand if the NO has a different effect in the diabetes case and why, mechanistically,”3 Dr. Schoenfisch said. Ultimately, Dr. Schoenfisch stresses that he and his research team are not trying to change the paradigm of already-existing blood glucose sensors. “We’re not trying to design sensors that are smaller or that have some new engineering feat. We’re interested in addressing the foreign-body response with chemical strategies to ultimately mitigate the foreign-body response to the sensor.”3

References

1. Centers for Disease Control and Prevention. 2014 National Diabetes Statistics Report. http:// www.cdc.gov/diabetes/data/ statistics/2014StatisticsReport.html (accessed February 18th, 2015). 2. Mayo Clinic. How to test your blood sugar. http://www.mayoclinic.org/diseases-conditions/diabetes/in-depth/ blood-sugar/art-20046628?pg=2 (accessed February 18th, 2015). 3. Interview with Mark Schoenfisch, Ph.D. 02/12/15. 4. Koh, A.; Nichols, S.P.; Schoenfisch, M.H. J. Diab. Sci Tech. 2011, 5, 1052– 1059.

chemistry

paving the way to a greener energy future

BY HOPE THOMSON

hen considering the world’s incredible energy needs, a great solution may come in a very small, very green package. As technology enables improved standards of living across the globe, the energy required to sustain these changes is steadily rising, and traditional fuel sources are increasingly disfavored due to their contributions to climate change and pollution. Alternative energy sources such as solar, wind and nuclear power can help the growing deficit, but lack of efficiency and general widespread opposition often damage their credibility. Most solar technologies utilize photovoltaic cells to convert sunlight to energy, but biofuels capitalize on nature’s ability to do the same conversion by photosynthesis. Photosynthesis is the process that plant cells use to produce food for the organism; water and carbon dioxide go into the cell, and light from the sun drives the chemistry that produces oxygen and fuels such as sugars, fats and oils. The oils can be extracted from plant cells using chemicals or sound waves and are then processed in a facility similar to today’s crude oil refineries. After processing, biofuels can be stored and transported in the same ways as traditional fuels and can power everything from cars to planes. Algal biofuels, or biofuels derived from algae, are of particular interest as aqueous algae can potentially produce as much as 60 times more oil than terrestrial plants. But in order for algal biofuels to enter the energy marketplace as a viable fuel source, the efficiency of photosynthetic oil production by algal cells needs to improve dramatically. A promising lead exists in the discovery that when deprived of nitrogen — an essential nutrient e— the green al-

gae Chlamydomonas reinhardtii produces increased amounts of oil. If oil production could be further optimized, algal biofuels could possibly reach efficiencies that would enable practical and realistic applications. These applications, however, may be a few years down the road. Dr. Leslie Hicks of the department of chemistry at UNC-Chapel Hill is part of a collaborative team of scientists Dr. Leslie Hicks researching C. reinhardtii and its role in enabling biofuel introduction to the energy market. “[Genetic] engineering in well-defined systems is challenging in and of itself,” says Dr. Hicks. “There’s not one gene that you can insert and it’s going to magically make a ton of [oil].” The overarching goal of the project is to obtain a clear understanding of the algal cell and how it produces oil, so that future manipulation of algal biofuels will be possible. In order to understand why C. reinhardtii under nitrogen deprivation produces more oil, the Hicks lab investigates the proteins involved in photosynthetic signaling pathways. The algae cell interprets external stimuli, such as nitrogen deprivation or excess sunlight, and then modifies the protein machinery in the pathway to produce altered photosynthetic products. The Hicks lab focuses on two protein modifications: phosphorylation, or the addition of a phosphorus group, and oxidation-reduction, also known as “redox”, or the addition and removal of an electron.

Carolina Scientific To see how the cell interprets phosphorylation and redox modifications, the Hicks lab investigates the photosynthetic proteins at various stages of nitrogen deprivation. After isolation and extraction of proteins, the search begins to determine which are active in photosynthesis, which have altered phosphorylation and redox behavior and where the sites of these modifications are. “Everything we do is analytical chemistry,” says Dr. Hicks, “but it’s very interdisciplinary, understanding the underlying biology.” The Hicks lab achieves this complex biological understanding by an analytical method called mass spectrometry, which provides puzzle pieces of information that can be used to stitch the structure of the protein back together. The exact location of each phosphorylation and redox site on the protein can then be pinpointed and monitored for changes over the various stages of nitrogen deprivation. Using this data, the Hicks lab can establish a correlation between different levels of nitrogen deprivation, alterations in the photosynthetic protein signaling pathways and increased oil production. The difficulty in this method extends past the already complicated protein puzzle. The proteins of interest, as well as the active phosphorylation and redox sites, are few and far between. Because they can be covered up by all of the other proteins detected in mass spectrometry, Hicks says the essential question is “How do you look at things with low abundance?” The group implements elegant enrichment methods involving a small bead in order to isolate their proteins of interest and amplify their signal. The method proceeds in a simple stepwise fashion. Proteins of interest are bound to the bead by a chemical reaction with a molecule on the bead. Once bound, everything else in solution is washed away, and the proteins can then be released from the bead for analysis by chemically breaking the previously formed bond. Isolation of phosphorylation and redox proteins differs in how they are bound to the bead. This research into C. reinhardtii is funded by the Department of Energy as an investigation into alternative energy sources, so the Hicks lab is working in tandem with scientists globally in order to further characterize the algae’s photosyn-

chemistry

thesis mechanisms. Coordinating meetings to discuss the research is sometimes challenging, as collaborators can be scattered across as many as six time zones. It seems, though, that this diversity contributes to the overall quality of the research. “It’s a good way to interface with people who are doing really different things from you,” says Dr. Hicks. “This research is so interdisciplinary it couldn’t be done by just one lab.” And to Dr. Hicks, working in a team on such a complex problem is a welcome task. “I like challenging puzzles…and I like using the power of the technology in difficult and interesting ways so we can answer questions that can’t be addressed by other techniques.” Hopefully, a few years down the road, the answers provided by Dr. Hicks and her collaborators will gift us with a brighter and cleaner energy future.

References

1. Department of Energy. Renewable Energy: Bioenergy, Energy 101: Algae-To-Fuels. http://energy.gov/scienceinnovation/energy-sources/renewable-energy/bioenergy. (accessed February 10th, 2015). 2. Slade, W.O.; Werth, E.G.; Chao, A.; Hicks, L.M. Electrophoresis. 2014, 35, 3441–3451. 3. Juergens, M.T.; Deshpande, R.; Lucker, B.F.; Park, J.J.; Wang, H.; Gargouri, M.; Holguin, F.O.; Disbrow, B.; Schaub, T.; Skepper, J.N. et al. The Regulation of Photosynthetic Structure and Function during Nitrogen Deprivation in Chlamydomonas reinhardtii. Plan. Physiol. 2015, 167(2), 558–573. 4. Wang, H.; Gau, B.; Slade, W.O.; Juergens, M.; Li, P.; Hicks, L.M. Mol. Cell. Proteomics. 2014, 13(9), 2337–2353. 5. Park, J.J.; Wang, H.; Gargouri, M.; Deshpande, R.R.; Skepper, J.N.; Holguin, F.O.; Juergens, M.T.; Shachar-Hill, Y.; Hicks, L.M.; Gang, D.R. Plant J. 2015, 81(4), 611–624. 6. Interview with Leslie Hicks, Ph.D. 02/05/15. 7. Nelson, D.L.; Cox, M.M. In Principles of Biochemistry, UNC-Chapel Hill Custom 5th ed..; Freeman Custom Publishing: New York, 2008.

Figure 1. A comparison of C. reinhardtii Figure 2. (and title image) Chlamydomonas, the algae being studied by Dr. cells before and after nitrogen depriva- Hicks and her collaborators. Image taken by a transmission electron microscope. tion. Oil present in the cell is indicated Images public domain. in red. Image courtesy of Dr. Hicks.

biology

PEACOCKING A social phenomenon in nightclubs and an evolutionary paradox By Camille Gonzales

Photo by Madison Berndt, CC-BY-2.0.

e is totally peacocking right now.” In other words, said male is in a dance club and dressed to impress females in the thriving setting of social nightlife. Such a term was coined from the mating process of male peacocks, which flash their ornamental plumage in an effort to gain the attention of a possible female counterpart. The more elaborate the feathers, the greater the likelihood that a peahen will be attracted to that particular male. The term has permeated day-to-day language and is often applied to a man’s appearance at a nightclub. Male peacocks’ ornamentation is a potential example of the effects of the Fisherian sexual selection process, the main mechanism examined in the theoretical research framework of Dr. Maria Servedio at UNC-Chapel Hill and Dr. Reinhard Bürger at the University of Vienna. Their collaboration is based on debunking the common assumption that sexual selection plays a role in speciation.2 The commonly held belief is that sexual selection is a driving force for

speciation. Often those who encourage this assumption may see this correlation and assume causation, as shown in this example given by Dr. Servedio, “closely related species have a lot of coloration — and, therefore, sexual selection is causing speciation.”1 Disparaging the common assumption by illustrating the effects of the Fisherian process is the basis of Dr. Servedio’s research. Instead of sexual selection assisting speciation and increasing the net amount of trait divergence, which would agree with the aforementioned common assumption that sexual selection aids speciation, Dr. Servedio is able to model the counterintuitive role of sexual selection via the Fisherian process.2 Dr. Servedio, an evolutionary biologist, explained Fisherian sexual selection as “the bare-bones basic form of sexual selection’s function.”1 Referring to Fisherian sexual selection as the null model for sexual selection can perhaps be better understood non-verbatim. “The Fisherian process automatically occurs because females have pref-

Dr. Maria Servedio erences as to what kind of male they would mate with and thus their offspring inherit both the preference and the trait, which leads to the exaggeration of preference and the signal. We examine the Fisherian process as a null model for sexual selection, as it always happens with non-random mating,” said Dr. Servedio.1 Consider a dress completely detailed with an array of sequins, elaborate embroidery and varying cloths incorporated into the bodice. The entire dress becomes a complicated ordeal, but if the embroidery, sequins and varying

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Carolina Scientific cloths were all unstitched and removed from the dress, what is left at the end is a plain dress. That plain dress is representative of Fisherian sexual selection as a null model, uncomplicated by other mechanisms that could contribute to understanding sexual selection. Fisherian sexual selection is the most basic form of sexual selection. Dr. Servedio, with her research on sexual selection, attempts to explain the topic with various mathematical models and graphic displays. From these, it becomes evident that sexual selection is, in itself, counterintuitive. As a female within a species has preferences toward a certain male phenotypic trait, that trait increases within the population. This idea is quite paradoxical since traits such as the flashy plumage of male peacocks are naturally selected against because of their cost to an individual, yet that preference trait is passed down through later generations of the bird species. Rather than assist species maintenance and speciation, Fisherian sexual selection is inhibitory to both because it erodes natural selection.2 For instance, pheasants are sexually dimorphic, meaning that the male and female pheasant can be readily distinguished based on their appearance. Female pheasants, in general, are not as large or brightly colored as male pheasants. While coloration, such as the red hue that encircles the eye region of the male bird, may be beneficial in attracting a female pheasant to mate with, it is also counterproductive since it makes the males more distinct to predators. Analogous to male peacocks, the

Figure 1. The male peacock courting a peahen. Photo by Andrew Cheal Photography, CC- BY- 2.0. colored plumage of pheasants has pro- tionary biology, specifically within the liferated through multiple generations, ramifications of understanding sexual although natural selection generally selection. The purpose of it all is that “it selects against such a trait due to the in- becomes more of a cautionary tale on creased risk of predation. The end goal how to be more careful ascribing defiis not to introduce a new evolutionary nite causation from correlation,” said Dr. concept, but rather expand and ascribe Servedio, contravening “the casual relaa better truth to the study of evolu- tionship between sexual selection and speciation.”1 The over-generalization of sexual selection discounts the chances that species maintenance could be differentiated based on whether sexual preferences within a species are weak or strong. If the common assumption might not be true in its entirety, then what exactly is the fate of species maintenance if sexual selection is not always an assistant to speciation?

References Figure 2. The male pheasant on the right exhibits a more colorful array in its feathering than the female on the left. Photo by Ian-S, CC- BY- 2.0.

1. Interview with Maria R. Servedio, Ph.D. 02/03/2015 2. Servedio, M.R., Bürger, R. PNAS. 2014, 111, 8113-8118.

biology

Genetic manipulation of cultured mammalian cells can provide insight into protein function. Shown are cultured mammalian cells from which a certain protein function was removed, resulting in dramatic alterations in cell shape. Image courtesy of Dr. Peifer.

By Katie Huber

ometimes the most interesting part of doing research is not knowing exactly what is most important about it. Dr. Mark Peifer and his lab at UNC-Chapel Hill are currently studying the cellular machinery used by fruit fly embryos and cultured mammalian cells. Their goal is to better understand morphogenesis — the process by which an animal’s body plan is developed — and how it is regulated. Morphogenesis can be compared to designing a piece of artwork, where art supplies are used and converted into a complex masterpiece. Dr. Peifer’s research has numerous potential applications, but sometimes it can be hard to predict the exact direction of these studies in the short-term.

“If myosin is like a motor, actin serves as a track along which myosin moves.” -Dr. Peifer

Dr. Peifer is a researcher of basic science who became interested in cellular biology while he was an undergraduate student. Research in basic science yields general knowledge that addresses a number of important problems. In contrast to translational research, however, basic science does not necessarily give a specific answer to any of those problems.1 Dr. Peifer “I’m in basic science because I want to know how things work, not because I’m trying to solve human problems. But I also think basic science plays an important role in solving human problems.”2 Dr. Peifer emphasizes the importance of scientists pushing forward

Carolina Scientific to build on knowledge in the field and also approaching that knowledge from different angles. Sometimes the most obscure scientific discovery can lead to myriad applications, and an important part of research is taking scientists’ broad questions and using specific discoveries from a particular field to find answers. “My field, in the super big picture, wants to know how cells change shape and move,” Dr. Peifer said.2 To answer that with specifics, the Peifer lab studies a piece of cell machinery known as the actin and myosin cytoskeleton. Actin and myosin are proteins that play a crucial role in muscle contraction in humans and animals. If myosin is like a motor, actin serves as the track along which myosin moves.3 Human cells use actin and myosin to generate force at the subcellular level. The Peifer lab studies this at the cellular level to determine how these proteins can pull on cell membranes to change a cell’s shape. Actin builds polymers in the shape of long rods that can grow and shrink. “They’re basically like the bones of the skeleton of the cell,”2 said Dr. Peifer. Myosin is a different protein that has the ability to generate force and move actin filaments around. Together, cells use actin and myosin to generate force at the

Dr. Peifer emphasizes the importance of scientists pushing forward to build on knowledge in the field and also approaching that knowledge from different angles.

Figure 2. This image shows how actin and myosin work together to contract and generate force. Photo by Slashme, CC BY-SA 3.0. microscopic level. Actin and myosin proteins need to be attached to the surface of the cell for it to change shape. Adherens junction are protein complexes for establishing this connection and for linking whole cells together. These links are formed in embryonic development and allow cells to change shape in a coordinated way. “One of the things my lab is studying is how you link the junctions to the actin and myosin cytoskeleton,” said Dr. Peifer.2 If one of these proteins is damaged or removed, the cytoskeleton can still change shape, but the link between the adherens junction proteins and the cytoskeleton is torn, and development can be disrupted. Many of these same proteins are mutated in human disease.2 Likewise, if these regulator proteins are involved in too much or too little activity, disease and developmental abnormalities including cancer can arise. The Peifer lab has the ability to address scientists’ general questions like how cells can change shape and move. Their lab thinks about not only how results apply in a certain time or place but, more generally, how cell machinery works. Through his analogy, Dr. Peifer explains: “if we want to understand how to fix a car, we need to understand how a car works.”1 This understanding is a crucial first step that may end up having applications in the medical field or in other fields that once seemed virtually unrelated. “It’s really hard to predict,” says Dr. Peifer.2 However, this is the most exciting thing about the work of the Peifer lab and about research in basic science – you never know what might be discovered next.

References Figure 1. Knowing where proteins are located in cells of fruit fly embryos can also show how these proteins function. Shown is an immunofluorescent image of a fruit fly embryo during a specific stage of morphogenesis. Cytoskeletal and adhesion proteins are found in this area. Image courtesy of Dr. Peifer.

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1. National Science Foundation. What is Basic Research? http://www.nsf.gov/pubs/1953/annualreports/ar_1953_ sec6.pdf (accessed February 23rd, 2015). 2. Interview with Mark Peifer, Ph.D. 02/02/15. 3. Lodish, H.; Berk, A.; Zipursky, S. L.; Matsudaira, P.; Baltimore, D; Darnell, J. Myosin: The Actin Motor Protein. In Molecular Cell Biology, 4th ed.; W.H. Freeman: New York, 2000.

biology

A colony of B. subtilis cells forms a biofilm on a solid agar surface. Image courtesy of Dr. Shank.

Bacterial Gossip how a game of telephone can prevent cannibalism BY SARAH MILLER

ou might be able to talk your sibling into becoming a cannibal. That is, if you are a Bacillus subtilis bacterium and the form of talking you use is secreting chemicals as means of interspecies communication. Dr. Elizabeth Shank, a researcher at UNC-Chapel Hill, is trying to translate this microscopic communication — a conversation that occurs not through sound but through chemical signaling molecules that cause bacteria cells to kill their own sisters. Research has shown that certain molecules secreted by B. subitilis cause bacteria to become these “cannibal” cells, and Dr. Shank wanted to know why.1 She also wondered whether other species of bacteria in the environment could join this intimate conversation and tell B. subtilis to turn into cannibals even when they normally would not.1 Dr. Shank’s research targets the microbial metabolites — molecules used in bacterial conversation — that affect the specialization of B. subtilis. She chose this bacterium as her experimental subject because it is ubiquitous in soil specimens all over the world. Dr. Shank devised an experiment to screen for other bacteria that make compounds which cause certain genes to be turned on, or expressed, during the development

of B. subtilis.2 Much like human cells differentiate into specialized cells such as skin or neural cells, B. subtilis cells also have many different specialties; however, each cell remains genetically identical. The types of cells Dr. Shank is researching are primarily those that form a biofilm (a bacterial film like the layer of goo on the surface of an algae-infested lake), those Dr. Elizabeth Shank that sporulate and those that swim. The biofilm-producing bacterium also serves another purpose: it is a cannibal and committer of “siblicide” — the killing of other “sister” bacteria in the colony.2 The B. subtilis that make the biofilm also produce a chemical toxin that only they can resist — even though the swimmers and sporulating cells are genetically identical, they do not express the genes needed to provide immunity to this toxin. The various B. subtilis cell types are presumed to be naturally selective in certain environments. There may be

Carolina Scientific

biology

Figure 1. Left: The glowing B. subtilis colonies actively express the operons required for biofilm formation. The nonglowing neighboring microbes produce the microbial metabolites that trigger this response.1 Right: This figure shows the interactions between B. subtilis and a soil microbe (large center colony). The soil microbe secretes a signal that turns on the fluorescent glowing tag in the B. subtilis colonies closest to it.1 Images courtesy of Dr. Shank. reasons that bacteria might want to convince their microbial neighbors to turn into these different cell types. For instance, Dr. Shank proposed that it would be more advantageous to be a swimmer when food is scattered around in the environment if you could convince your competitor to make a biofilm and become trapped against a surface. Biofilm differentiation might also create a symbiotic relationship among the different bacterial species — for instance, the biofilm could provide protection and the close proximity of cells could allow for more efficient use of resources.2 Dr. Shank is interested in how other bacterial species might impact the ability of B. subtilis to form these different cell types. Do other bacterial species produce chemical signals that can convince subtilis to turn into In understanding how B. biofilm-forming cells?1 metabolites influence To answer this question, Dr. Shank created neighboring cells, a methodology to deDr. Shank might gain tect which neighboring microbes in the the knowledge to use do more than their microbial conversation soil share of neighborly for human advantage. duties. She tracked the activation of the genes needed for making the biofilm-cell type when they were expressed in B. subtilis. When a certain gene is activated, B. subtilis is provoked to activate, or “transcribe,” the biofilm gene, changing the cell into a biofilm-matrix-producing cannibal. Dr. Shank tracked the activation of these genes by creating a modified B. subtilis strain that glowed when biofilm operons were activated. The nearby colonies of non-B. subtilis could be identified as the producer of the compound that activated the operon, and thus influenced the DNA it copied and the function of the bacteria. Using this method, Dr. Shank identified the

neighboring microbes that caused these biofilm-specific traits to be expressed. The genes activated and traits expressed are significantly correlated with the “phylogenic relatedness” of the bacteria to B. subtilis, meaning that the closer the relation of a certain microbe to B. subtilis, the higher the chance that it encourages B. subtilis to create biofilms and the antibiotic.2 Although this process occurs on a microscopic scale, its potential applications are significant. For instance, microbes are the driving force in the carbon and nitrogen cycles, both of which are important in crop yield. Discovering which metabolites are associated with maximum crop yield could lessen the need for pesticides or other unhealthy farming practices. Microbial communication research also has the potential for clinical advancement. Several medicines, such as the commonly known compound bacitracin (an antibiotic in Neosporin), are derived from bacteria to fight other bacteria. The compounds used to trigger responses in neighboring microbes could serve a similar purpose, but first we have to figure out the meaning of the “words” they represent in this microbial conversation.1 In studying the microbial metabolites that affect the development of B. subtilis, Dr. Shank found that the more closely related a microbe is to the subject species, the more likely B. subtilis is to kill part of it own colony and form a biofilm. But why? She points out that with every experiment, every result and every conclusion, many more questions arise. “It makes you want to go back and find a new method to understand that [the new questions] … You have to find the whole story,” Dr. Shank said1. In understanding how metabolites influence neighboring cells, Dr. Shank might gain the knowledge to use microbial conversation for human advantage.

References

1. Interview with Elizabeth Shank, Ph.D. 02/03/15. 2. Shank, S.; Klepac-Ceraj, V.; Collado-Torres, L.; Powers, G.E.; Losick, R.; Kolter, R. PNAS 2011, 108(48), E1236–E1243.

biology

unveiling the basics behind

MOLECULAR MOTORS BY SAHANA RAGHUNATHAN

Illustration by Tatihana Moreno

ne of the most basic human instincts is movement: From newborn infants to senior citizens, movement is natural, and it boils down to cellular mechanisms. The properties and characteristics of myosins, a class of motor proteins involved in many types of cellular movement, are heavily studied throughout the world. Dr. Richard Cheney in the department of cell biology and physiology at UNC-Chapel Hill specializes in studying these myosins and has delved deeply into their mechanisms. Dr. Cheney became interested in

researching motor proteins due to his early fascination with the molecular basis of movement. After deciphering the functions of myosin-V during his postdoctoral work at Yale, he is now diving into the deep ocean of information myosin-X seems to hold. As a superfamily of motor proteins, myosins move along their actin filament â&#x20AC;&#x153;tracksâ&#x20AC;? to transport cargo from point to point in a cell. The different types of myosin accomplish many cell processes such as regulating brain functions, forming neuronal connections, producing blood vessels and assisting with skin pigmentation.1

Myosin-X is especially important for forming fingerlike cell protrusions, called filopodia, which cells use for extracellular sensing and movement. MyDr. Richard Cheney osin-X localizes to the tips, as seen in Figure 1. The 37 types of myosins have widely varying functions throughout the human body. One of the most wide-

biology

Carolina Scientific ly known myosins, myosin-II, is extremely important for muscle contraction and movement.1 When myosin-II molecules receive electrical signals to contract in muscle cells, thousands of them work together to start “walking” along actin filaments to shorten the muscle cell, leading to muscle contractions. At the same time, calcium ions are released into the cell’s interior. Once all the calcium ions are pumped back into their original location (an organelle called the endoplasmic reticulum), the myosin heads let go of the actin filaments and stop the contraction. However, if mutated, myosins can

“Being on the edge is difficult at times, but it’s also a fun place to work.” -Dr. Richard Cheney lead to many problems in the body. Dr. Cheney’s work is funded by the Deafness Institute, as myosin mutations play a significant role in hearing problems, but this is not the only potential issue.1 “Recent work from cancer labs has implicated myosin-X in the many human cancers, and it seems to be particularly important for the cellular spread and ability to invade tissues,” Dr. Cheney said.1 Research has shown that levels of myosin-X and one of its main binding molecules are highly upregulated, or increased, in tumorous tissues in breast cancer patients. One major obstacle involved in pursuing the mechanisms of myosinX in cancer is the fact that most previous work has been focused on studying myosin-X in individual cells in a dish.1 Dr. Cheney and his collaborators have been taking new steps to examine its function in live organisms. They have been working on making a myosin-X “knockout” mouse for almost ten years, and have made significant progress towards that goal. “Knocking out” a gene involves completely removing it from the organism’s genome. A major difficulty involved in knocking out genes is that there is no certainty that anything will be wrong in the organism. Dr. Cheney

Figure 1. The structure of myosin, which helps contract muscle cells by sliding along actin filaments. Image from Protein Data Bank, in Houdusse, A., Kalabokis, V. N., Himmel, D., Szent-Gyorgyi, A. G., Cohen, C.: Atomic structure of scallop myosin subfragment S1 complexed with MgADP: a novel conformation of the myosin head. Cell 97 pp. 459 (1999).

Figure 2. Myosin X, fluorescently labeled in green, localizes to the tips of filopodia in cells. Image courtesy of Dr. Cheney. states, “Sometimes you knock out genes that appear to be very important and the animals appear to be fairly normal, and in other cases you can knock out a gene you think is fairly harmless and the animals die before they are born, so understanding what the gene is actually doing in an organism is an important question.” However, this is a project that could possibly give researchers new insight into cancer biology. Dr. Cheney has studied the many different types of myosin for years, and he has made a lasting impact on the biomedical research community through his discoveries involving myosin-V. He

hopes that his research on myosin-X, which he describes as “incredibly fun,” will be as popular and impactful. His current work pushes the limits of biomedical research, and “being on the edge is difficult at times, but it’s also a fun place to work.”1 The boundaries of cancer biology research are continually expanding, and myosin-X might be the next hot topic.

References

1. Interview with Richard Cheney, Ph.D. 02/11/15.

biology

To Feed Every Mouth By Ivy Somocurcio

t a glance, the United States’ food supply may seem limitless. However, before worldwide produce is even distributed to markets, about 40 percent of the crops die of disease by viruses or fungi.1 As the population continues to grow, so does the ratio of people to produce. While insecticides and pesticides can protect crops from insect and bacterial damage, protecting plants from other pathogens is a more challenging endeavor. Viruses are composed of DNA or RNA encased in a protein coat. Because they are incapable of reproducing on their own, viruses use cells as their hosts, injecting their nucleic acids and manipulating the host’s nucleus to make copies of the virus. After the cell generates a large number of new viruses, they burst

out of the cell, rupturing it, and find a new host. For plants, this kind of pathogenic destruction causes cellular damage and contamination to the water absorbed for plant development.2 To improve these plants’ defense mechanisms, biologist and immunologist Dr. Jeff Dangl conducts research to reprogram plants’ immune systems. This work started after he stumbled upon a paper on plant cells’ changes in gene expression affecting defense. Having noticed the lack of research in the area, he used the paper to develop the framework for his own study.1 Since then, he has made some of the first chimeric DNA-based antibodies, given a new function by combining DNA fragments of the plant Arabidopsis thaliana, also known as thale cress, and another

Illustration by Kristen Lospinoso species. He uses A. thaliana as a model due to its short generation time and low number of chromosomes. Because it reproduces quickly, cloning genes of the plant is relatively easy as well. To identify the function of a certain gene, Dr. Dangl and his lab create mutant plants in which the specified gene is “knocked out”. One way of creating such a mutant is by breeding plants with and without the mutants to produce mutant alleles, or gene variants.1 Through observation of the phenotypic, or physical, differences between the mutants and non-mutants, the lab can determine the gene’s function. When the lab repeats this experiment with different mutants, they can assemble a map to identify the protein pathways affected by differenc-

biology

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Figure 1. Arabidopsis. Photo by Brena. CC-BY-SA 3.0. es in gene expression. If one protein is knocked out of a pathway, but a phenotypically normal plant results, then there must be a protein preceding the missing protein in the pathway that allows for a normal phenotype.1 Such a process has allowed the Dangl lab to draw out an immune response pathway in Arabidopsis. “Plants cannot run away and hide. They’re stuck in one place for their entire life,” Dr. Dangl said.3 Also, they do not have circulating cells that send messages from one part of the plant to another. Due to these limits, plants have evolved a complex immune system that differs from ours. Once a threat lands on a cell, proteins embedded in the cell surface bind to others below to activate defense mechanisms.3 Like a game of telephone, proteins send messages over long ranges by communicating locally with other proteins in specific pathways. Sometimes, however, these pathways are hindered. Viruses, for example, can remain incognito by releasing molecules to block or slow protein binding, permitting their proliferation.3 However, plants have evolved a “plan B,” which the Dangl lab has further investigated. “Plan B” is another pathway in which specific proteins recognize virus-emitted molecules and take them on in an extreme way: cell death. A plant cell can sacrifice itself in a separate pathway, taking down the pathogens with it and therefore preventing them from spreading to other cells. While this tactic prevents the pathogen from dispersing to adjoining plants, it still accounts for significant produce loss. One of Dr. Dangl’s current research goals is to modify the pathway to permit alternative immune responses over cell sacrifice.

Currently, the lab continues to map genes to observe additional pathways and unravel the entire Arabidopsis genome.1 However, this project comes with obstacles. Arabidopsis may be a model organism, but it is not perfect. Its genome has been completely duplicated twice in its evolutionary history, and consequently, 60 percent of its genes exist in two places.1 This means that knocking out a gene in one site can still produce a normal phenotype if its function overlaps with that of a gene located elsewhere in the genome.1 Once the immune pathways have been mapped clearly, Dr. Dangl’s lab will be able to easily manipulate the genome. For example, Dr. Dangl wants to create a plant that allocates its energy equally between defense and growth.1 With such a balance, the plant would be sufficiently resistant to pathogens while reproducing at an optimal rate, thus increasing

the net produce harvested. Mapping plants’ immune pathways is key to modifying the genes that drive them, and along the way, new discoveries about plant genomes may be made. Through meticulous investigation of the mechanisms, scientists like Dr. Dangl can engineer plants to be stronger than pests.

References

1. Interview with Jeffery L. Dangl, Ph.D. 02/04/15 2. Coll, N.S.; Epple, P.; Dangl, J. L. Cell Death Differ. 2011, 18(8), 1247–1256 3. Dangl, J.L.; Horvath, D.M.; Stashawicz, B.J. [Podcast]. 2013. http://labs. bio.unc.edu/Dangl/pub/pdf/Science_Podcast_JLD_AUG16_2013.mp3 (accessed Mar 15, 2015).

Illustration by David Wright

biology

one fish,two fish...

No Fish if You Overfish By Seth Bollenbecker

Image courtesy of Abel Valdivia.

ish are disappearing off the menu faster than you can take your seat at a seafood restaurant. Overfishing, caused by catching more fish than a certain population of marine life can replace through natural processes, is a pertinent problem in Earth’s waters.1 For decades, studies have been taking place to obtain estimates for the severity of the practice. However, few have addressed factors such as preexisting environmental bias towards certain fish populations. Abel Valdivia is a Ph.D. candidate at UNC-Chapel Hill working in the John Bruno Lab to find a connection between the amount of fish in the Caribbean Sea and the combined effect of human activities and environmental dispositions. “Over time, new generations see the ecosystems that they are able to visit

as the baseline. [They] do not have a reference point of what the ecosystem looked like fifty years ago,” Valdivia said.2 Current data suggests that an area with very few fish could be a victim of overfishing, and many studies have concluded that overfishing is the sole cause. However, some of these sites may naturally only be able to support a small number of fish due to the environment or ecosystem stability. In order to combat the lack of an established baseline in many places, Valdivia set out to correct the problem by finding out what was considered normal in reefs and other marine areas. Valdivia’s study compared relationships between the biomass of the fish in a given area and multiple variables. First, the data was used to predict variance among study sites related to

Abel Valdivia human impacts and natural factors. Second, historical baselines were estimated based on the data with human influences removed.1

biology

Carolina Scientific A native of Havana, Cuba, Valdivia has been seeing the effects of overfishing since he was very young. Growing up on an island in the Caribbean, the fishing industry was always present. Valdivia recalls spearfishing when he was younger and realizing that after a few days of being in a certain area, he would have to move to another spot farther out to have large fish available again. Applied on a global scale with a little more scientific evidence, Valdivia’s overfishing research perspective can be traced back to his childhood experiences. His project has not been without challenges. Getting research permits, for example, can be an arduous task, de-

“My research is based on almost 40 sites across the Caribbean, and every single country is different.” -Abel Valdivia pending on how favorable the country is to research. “My research is based on almost 40 sites across the Caribbean, and every single country is different,” Valdivia said. Permits that may take a few weeks to obtain in the Bahamas may take much longer in Cuba, for example, and there are far fewer resources available as well.2 Despite the setbacks, Valdivia has completed a study that took a set of 29 variables into account when analyzing fish amounts in coral reefs. The study found that over 50 percent of variability of total fish mass was linked to nonhuman factors that included abundance of prey and complexity of the reef. This shows that overfishing, while a problem in the decline of fish populations, is not the only factor that determines the abundance of fish in a marine ecosystem. Based on the data collected from the study, Valdivia was able to conclude that predatory reef fish have declined 80 to 90 percent in most of the sites, even within reserves dedicated to protecting the populations. Valdivia’s research designates natural predator “hot spots”

Figure 1. (Above) Groupers are among the top predatory fish most commonly fished in the region (black grouper, Mycteroperca bonaci). Image courtesy of Fausto De Nevi. (Below) The great barracuda (Sphyraena barracuda) is a top predator that is primary targeted by fishers, even thought is known for having ciguatera fish poisoning in few areas across the region. Image courtesy of Abel Valdivia. to target and increase preservation efforts.1 Valvidia’s research associates the decline in fish populations with natural factors, suggesting that these fish may be even more vulnerable to overfishing by humans. However, from afar and without any connections to fishing or wildlife protection areas, there is not much an individual can do about overfishing. Even so, advocates for any cause can result in media attention which pressures against harmful fishing habits. Individuals can help by spreading the word about which diminishing fish species to avoid buying. Guides also exist to let consumers know which fish not to choose when eating at a restaurant or when fishing on their own. However,

Valdivia said few of the existing resources highlight specifically which reef fish to avoid. It seems that the large differences in fish abundances across the world can be attributed to a combination of human and environmental causes, but the exact role of each remains to be fully understood. For now, dramatic changes in certain seafood menus are in order.1

References

1. Valdivia, A.; Cox, C.; Bruno, J. 2015, PeerJ PrePrints 3:e805v1 http://dx.doi. org/10.7287/peerj.preprints.805v1 (accessed Mar 15, 2015). 2. Interview with Abel Valdivia. 02/09/14.

Sixteen years ago, scientists began undertaking the endeavor of indentifying and maintaining an inventory of the thousands of species in the Great Smoky Mountains of NC. Image courtesy of Dr. White.

Title

By Firstname Lastname

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TAKING INVENTORY of life By Arantxa Lopez de Juan Abad

he Earth is home to all living things currently known to man. Some of them live among us, in our home or backyard, while others are too far away to experience — and many more still remain to be discovered. Now imagine being able to know exactly what living things are around us, from the bacteria in the soil to the top predator of the food chain. At North Carolina’s Dr. Peter White Great Smoky Mountains, that is becoming a reality thanks to the All Taxa Biodiversity Inventory (ATBI). An endeavor by the non-profit organization Discover Life in America, ATBI aims “to inventory the estimated 100,000 species of living organisms in Great Smoky Mountains National Park and to develop checklists, reports, maps, databases and natural history profiles that describe the biology of this rich landscape to a wide audience.”1 This project is not only one of a kind and unprecedented in scope,1 but also rooted in Chapel Hill. Peter White, a professor in the biology department, has done forest ecology research in the park for over 30 years and was called on to the project because of his experience. According to Dr. White, this project is something “that has not been attempted very often.”2 The project began in 1999, when a similar endeavor was attempted in Costa Rica. Keith Langdon, the founder of the project, used the same idea of an inventory and brought it to the Great Smoky Mountains National Park due to its high biodiversity. Dr. White was one of the founders faced with the task of starting this ambitious endeavor — one that had never succeeded before. Dr. White was in charge of writing the Scientific Plan of the ATBI, which meant drafting the set of questions that needed answers and the structure of the project as well as stating the importance of the project. This had to be different from traditional observations of species, which taxonomists had been doing in the park for years. Dr. White wanted to quantify efforts of data collection in order to normalize the number of

biology species counted. His Scientific Plan implemented “structured sampling and observation,” or the creation of a series of observation points where the effort of the sampling was controlled. Afterwards, Dr. White’s involvement continued as fieldwork through his students’ research, and he acted as a spokesperson for the project. Dr. White describes the ATBI as “an exciting attempt to list every kind of living thing in the specific geographic area.”2 This list includes everything from plants and animals to bacteria and nematodes. The high biodiversity of the park, which straddles the border between North Carolina and Tennessee, can be attributed to the fact that it has undergone the least disruptive change throughout time by remaining above sea level and therefore escaped glaciation for millions of years.2,3 The project will contribute to general scientific knowledge by shedding light on species yet unknown to us. “It’s amazing how little we know about biodiversity on Earth,” Dr. White said.2 For conservation biology to work, the scope of species that exist must first be known. Furthermore, the ATBI will help to determine rarity of species, the niche of each species in the natural community, the abundance of each species as the seasons change and the species’ ecological roles and interactions. The large database will help scientists study other aspects of biodiversity, such as the effects of climate change, pollution and invasive species on habitats and living organisms. The ATBI is now in its 15th year and has already presented major findings. The research has led to the discovery of 7,799 new species in the park and 931 new species previously unknown to science. The database is dynamic, as research is ongoing and the number of species always subject to change. Currently, 18,200 species have been identified in the park. Despite not having a deadline for completion, the project has shown success in its contribution to science and the enthusiasm that surrounds it. Furthermore, the ATBI supports other aspects of the scientific community by supporting museums, universities and students. Dr. White describes the ATBI as like filling up a library: the more information it contains, the more useful it is to everybody else.2 A diverse group of about 200 people, including scientists, educators and artists, has been involved throughout the duration of the project. The database is made possible by the contributions of past individual research projects as well as current efforts. The National Park supports the endeavor, and other contributions come from various sponsors as well as individual grants to specific scientists. As science continues to run its course in the Smokies, we can continue to await the discoveries that the ATBI offers to science and to our vast, but not yet complete, pool of knowledge.

References

1. Discover Life in America. http://www.dlia.org (accessed March 18th, 2015). 2. Interview with Peter White, Ph.D. 02/11/15. 3. Fifteen Years of Discovery. http://www.dlia.org/Communications/dlia_whitepaper_15years_final.pdf (accessed February 9th, 2015).

Biodiversity in the Smokies. From top to bottom: 1. Keith Langdon temporarily puts down his butterfly net. Langdon was the organizer of the ATBI, at the time a park service employee who headed inventory and monitoring for biodiversity in the park. 2. A Turk’s cap lily in the Smokies. 3. Dying hemlock trees from the introduced Asian pest, hemlock woolly adelgid. Environmental changes and threats are one of the motivations of the ATBI to create a benchmark to understand change. All images courtesy of Dr. White.

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technology

NANOTECHNOLOGY knocks on the door of drug delivery by Nathan Lunsford

article Replication in Non-wetting Templates, known as PRINT® technology, is a mold-based replication process developed in Dr. Joseph DeSimone’s lab in UNCChapel Hill’s chemistry department. PRINT fabricates particles with precise control and has significant applications in drug development. The process of PRINT is as follows: a unique liquid is poured over a template to form tiny cavities that another liquid — such as the precursor to a vaccine — can fill. After the liquid in these cavities solidifies, the 2-D array of particles is stripped of the template and can be used to develop high-performance, cost-effective vaccines and medications (Figure 1).1 “We believe PRINT is a powerful tool for the controlled synthesis of precision particles useful for design of new therapeutics and vaccines. My students have been successful driving the technology forward by successfully melding various disciplines seamlessly and through their close collaboration with Liquidia Technologies in RTP,” Dr. DeSimone said.2 A Chancellor’s Eminent Professor of Chemistry and 2008 Lemelson-MIT prize winner, Dr. DeSimone launched Liquidia Technologies in 2004, which was backed by the first ever biotech equity investment by the Bill and Melinda Gates Foundation.3 Liquidia has since converted the PRINT process to conform to guidelines for food and pharmaceutical practices. Thus, the company has been able to bring their first product, a PRINT particlebased seasonal influenza vaccine delivery system, into clinical trials.4

Dr. Joseph DeSimone

Figure 1. PRINT® technology uses a mold-based replication process to develop cost-effective vaccines and medications. A unique liquid is poured over a template to form tiny cavities that another liquid — such as the precursor to a vaccine — can fill. After the liquid in these cavities solidifies, the 2-D array of particles is stripped of the template and can be used for applications. Image courtesy of UNC Chemistry. References

1. DeSimone Research Group: UNC and NCSU. PRINT (Particle Replication in Non-wetting Templates). http://desimonegroup.chem.unc.edu/?p=195 (accessed February 7th, 2015). 2. Email with Joseph M. DeSimone, Ph.D. 02/12/15. 3. Chemistry: Joseph DeSimone. http://www.chem.unc.edu/people/faculty/desimone/index.html?display=research_ display&show=all (accessed February 6th, 2015). 4. DeSimone Research Group: UNC and NCSU. Joseph M. DeSimone. http://desimone-group.chem.unc.edu/?cat=14 (accessed February 6th, 2015).

mathematics

Thrips in flight. The wingspan of the thrip is about 1 mm. It flies at a Reynolds number of about 10, and its wingbeat frequency is 200 Hz. Image courtesy of Dr. Laura Miller.

THE SYRUP IN OUR VEINS tiny organisms experience viscosity, not inertia BY COREY BUHAY

human embryo’s heart begins as a slender tube about the size of a hair. It’s a filament of blood, a tiny red wire. At such small scales, human tissue doesn’t have enough mass to hold its own against the thick fluid. Dr. Laura Miller at UNC-Chapel Hill uses mathematics to model the relationship between organ size and fluid thickness, or viscosity. Embryonic hearts are just one area of her research. Some scientists think an embryo’s heart shunts blood through the lentil-sized fetus by squeezing it along like a tube of toothpaste. Others think it works by suction.1 Regardless, valves and chambers are futile at such scales. An adult heart uses muscular force and fleshy gateways to move blood, which swishes and flows as one might expect. On a microscopic level, though, blood behaves differently. It oozes rather than flows, and the expanding and contracting heart would, at this scale, push and pull the fluid in place without pumping it anywhere. Keep in mind the actual viscosity doesn’t change as size decreases — it’s the experienced viscosity of the organ that changes. An embryonic heart doesn’t experience blood. It experiences corn syrup.2

Dr. Laura Miller’s office is tucked in the back of her lab on UNC’s campus. She works with the Mathematical Physiology Group there, modeling fluid movement at tiny scales. She sits down at a table in the well-lit office and drops a rectangular brick of plastic on its surface. It’s part of a larger-than-life model of an embryonic heart, genDr. Laura Miller erated by a 3D printer and, aptly, dyed red. It’s the reddest thing in her office. The walls bear photos and paintings of jellyfish in cool colors. The chairs are blue. The organizational boxes on her bookshelf are blue. Her eyes are blue. It’s easiest to explain fluid behavior by starting in a world bluer and colder than that of an occupied womb. To explain an embryonic heart’s experience of honey-thick blood, we have to start in the ocean.

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mathematics

Figure 1. Dye visualization showing the direction of flow in simple chambers that model the ventricle in embryonic hearts. Flow is from left to right, and the Reynolds numbers (Re) are approximately 0.1, 10, 40, and 100. The presence of chamber vortices can be seen for Re > 30. Image courtesy of Dr. Miller. Plankton — like bacteria, crab larvae and jellyfish polyps — have a lot of trouble moving from place to place. If a human were shrunk to microscopic size, swimming underwater would be impossible. Imagine breaststroking through molasses. Your arms are out in front of you, and pulling them to your sides propels you forward. But the momentum from that pull isn’t enough to keep you going through your thick surroundings; you stop almost immediately. When you drag your arms back in front of you for the next stroke, the movement pushes against the molasses enough to propel you backwards — right back where you started.3 This is what comparatively high viscosities can mean for tiny organisms. The smallest of the small have come up with clever ways to move about – everything from corkscrew-shaped appendages that spiral through the water to tiny cilia, which means “eyelashes” in Latin, that wiggle around the edges of the cell, an energetic row of jazz fingers to propel it through the water.3,4 Even so, they can’t move well, and what movements they do accomplish require almost too much energy to make that motion worth it. This is what’s called a “low Reynolds number” environment. The Reynolds number is the ratio of an object’s size to the viscous forces acting within a fluid, though it also depends on how fast the object is moving. A low Reynolds number means the viscosity that an organism experiences far outweighs any momentum it might be able to build up. In contrast, high Reynolds numbers define the realms of whales in deep water or birds hurtling through the air. It’s easy to build up momentum and ride it through a high Reynolds number world. This is the world of the fist-sized heart that shoots blood through veins and arteries without breaking a stride. Microscopic hearts, like those of sea squirts, minuscule fish and human embryos, however, have to operate on a different level. Learning more about fluids at embryonic scales can help scientists and doctors better understand human development and what conditions a growing fetus needs. But the same concepts apply to mechanics that operate far outside

the human body — in the orchards and fields of agricultural America. For human beings, air seems too insubstantial to hinder our steps, but to tiny insects, the thickness of air is far from trivial. Thrips are minuscule flying pests — only about a millimeter in length. Parasitic wasps are minuscule flying pest controllers. Farmers are very interested in both, but since they are too small to move efficiently, they tend to drift in and out of farms on the wind. The bugs can control their destiny only a little, so it’s hard to predict where they’ll end up.2 What movement they can control could be important in figuring out what winds they’re riding. That’s where Dr. Miller comes in. She started out as a biologist. “I eventually felt like I couldn’t answer the questions I wanted to unless I learned more math,” she said. When she asked colleagues how math could help understand animal flight, they told her about thrips, which do too much damage to ignore but are too small to track easily. Math, however, could be useful in figuring out how they move and therefore where they might end up.2

It’s easiest to explain fluid behavior by starting in a world bluer and colder than that of an occupied womb. To explain an embryonic heart’s experience of honey-thick blood, we have to start in the ocean.

Figure 2. A local species of thrips with a body length of about 1 mm. The bristled structure of the wings is characteristic of most tiny insects that fly at Reynolds numbers below 20. The air acts like a very viscous fluid at this scale, and there is little flow between the bristles. Image courtesy of Dr. Miller.

mathematics Dr. Miller switched her focus from zoology to mathematics, got her Ph.D., and set to work on tiny insects. Among her lab’s accomplishments is the first successful video of thrips in flight. They had help from UNC biology professor Ty Hedrick and his high-speed 3-D camera, which shoots about 4000 frames per second. To get enough light at those shutter speeds, Hedrick had to direct a beam through the camera’s macro lens with a magnifying glass. Even then, getting the video was no easy feat.2 “They have to prepare for flight,” Dr. Miller said, sounding just a touch exasperated with the high-maintenance insects. You can’t just shake them off a pipette; they’d fall. They have to want to fly, and they get ready to do so by rubbing their wings together to straighten the hairs that line the edg-

Dr. Miller’s lab has extended their mathematical models to studying the movement of moon jellyfish and the flow of blood through an unfathomably small embryonic heart. es. Those hairs are so fine that air, viscous as it seems at that size, can leak through the bristles during certain parts of the wing stroke. The leakiness reduces drag forces on the wings the same way a hand can move faster through water with outspread fingers than with a flat palm.2 Rubbing those hairs out straight is akin to spreading apart one’s fingers. Watching the thrips crawl up and down pipettes for hours a day paid off. Dr. Miller and her lab got the video, and it shows the perfect, elegant stroke the thrips have mastered to get off the ground. It’s called the “clap and fling,” which sounds more like an 80s dance move than the secret to what should be impossible flight.5 To better model that movement, Miller and her lab built a larger-than-life thrip out of plastic. To compensate for the increase in mass and still mimic the viscosity a thrip experiences, they submerged the model in corn syrup.2 “The good thing about corn syrup is it’s water soluble, so you can just use water to clean it up, but things can still be sticky for a while,” Miller admits. She says it’s better than oil, which they used to use. She also conceded the irony of her sugar-submerged model attracting actual flies.2 Dr. Miller’s lab has extended their mathematical models to studying the movement of moon jellyfish and the flow of blood through an unfathomably small embryonic heart. Dr. Miller pointed to the red plastic brick she had dropped on the table earlier. It had a corrugated scoop in the side like a bite mark.2 It was a heart chamber in the process of forming.

Figure 3. Fluid moves through a sea squirt heart, causing the tube of the circulatory system to flare and contract. Here the fluid is moving in a counter-clockwise direction, as indicated by the arrows. Image courtesy of Dr. Miller. “Eventually the atrium and ventricle start to bloom out of the tube,” she said, motioning to the ridged cave in the model. That’s how the heart starts to develop. As the embryo grows, the Reynolds number increases with it. The squeeze tube heart structure is no longer sufficient to pump blood, which becomes rapidly less viscous in comparison to the momentum the body can now build up. As the embryo outgrows the small Reynolds number world, it adapts. The tube bulges. Those bulges grow and split, and shape-shift slowly in chambers with working valves. The heart beats.

References

1. The Mathematical Physiology Group at UNC. Fluid Dynamics. http://miller.web.unc.edu/fluid-dynamics/ (accessed February 16th, 2015). 2. Interview with Laura Miller, Ph.D. 02/03/15. 3. Lopič, N.; Vilfan, M. Flagella and Cilia: Motility at Low Reynolds Numbers. http://mafija.fmf.uni-lj.si/seminar/ files/2011_2012/1-Flagella_and_cilia_-_motility_at_small_ Reynolds_numbers.pdf (accessed February 16th, 2015). 4. Cole, S.A. Design of Two-Tailed Swimmer to Swim at Low-Reynolds Number. B.S. Thesis, Massachusetts Institute of Technology, 2009. 5. Miller, L.A.; Peskin, C.S. J. Exp. Biol., 2009, 212, 3076– 3090.

Carolina Scientific

technology

Not Quite the Iron Lung

by Nathan Lunsford

NC-Chapel Hill has collaborated with researchers at the Research Triangle Institute (RTI) International to develop a “lungon-a-chip,” a microdevice mimicking the structure of airway tissue. The lung-on-a-chip employs three types of primary human lung cells to enable labs to study lung function and respiratory diseases. “The development of this microfluidic lung model, as well as other organs-on-chip, holds the promise of improving the physiological relevance of cellular models for more accurate prediction of the effects of toxicants and drugs on humans, and for reducing the use of animals in medical and pharmaceutical research," said Sonia Grego, Ph.D., research scientist at RTI and the project's principal investigator.1 The “lung on a chip” consists of three vertically stacked fluidic microcompartments separated by membranes with very tiny pores. The model was shown to support viable cultures of sensitive primary cells of the lung, which reproduced lung cell functions and properties such as mucus secretion.2 "These properties are critical for inhalation toxicology and drug studies,” said Katelyn Sellgren, Ph.D., a postdoctoral research scientist at RTI. Studying the mucosal airway modeled by the lung-on-achip can aid in understanding diseases such as asthma, chronic bronchitis and emphysema.

References

1. Novel lung-on-a-chip developed. http://www.sciencedaily.com/releases/2014/08/140814191229.htm (accessed February 6th, 2015). 2. Sellgren, K.L.; Butala, E.J.; Gilmour, B.P.; Randell, S.H.; Grego, S. Lab Chip 2014, 14(17), 3349–3358.

The Plastic Bag that Saves Lives

By Sara Edwards

or people in developing countries, determining the quality of drinking water may depend on a device that looks like nothing more than a glorified Ziploc bag. The compartment bag test (CBT) is an ingenious water-testing device that may not look like much, but it is a game changer when it comes to the health of communities in developing countries. “The whole premise of the test is to be applicable in practical situations in the developing world,” says Mark Sobsey, professor of environmental science and engineering at UNC-Chapel Hill, who developed the CBT along with a team of students, researchers and entrepreneurs.1 In most cases, determining whether or not water is safe to drink requires a laboratory and bulky, expensive machinery such as an incubator. These commodities are often difficult to come by in places without air conditioning or even electricity. The CBT is revolutionary to public health in the developing world because it can be used on-site and is just as accurate as standard testing devices.3 The bag itself is split into five chambers into which a sample mixed with a growth medium is poured. Left overnight, any E. coli in the sample will grow and turn the liquid blue. The number of chambers that turn blue corresponds to bacteria levels in the water source, determining how safe it is for humans.2 In addition, the built-in decontamination system makes the kit safe to dispose of after testing. The CBT, marketed through the UNC-based company Aquagenx, has already been used by companies and aid organizations in places like Haiti, Thailand, South Africa and Peru. “We would like to make sure [people in developing nations] are aware of the test,” says Sobsey, who believes the CBT will come into more widespread use in the future.1

References

Figure 1. The compartment bag test helps people in developing nations determine if their drinking water is contaminated. Image courtesy of Dr. Sobsey.

1. Interview with Mark Sobsey, Ph.D. 02/05/15. 2. Aquagenx. http://www.aquagenx.com/ (accessed February 3rd, 2015). 3. McMahan, L.; Wang, A.; Rutstein, S.; Stauber, C.; Sobsey, M.D. Presented at Annual Meeting of the American Society For Tropical Medicine and Hygiene, Philadelphia, PA, December 4–8, 2011; 571.

physics

the GRAVITY of Learning Physics BY MAI RIQUIER

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physics

he application of physics and astronomy research at UNC-Chapel Hill not only helps students comprehend challenging scientific concepts, but also turns students into “fans of science” the same way that people become fans of a sport. The Physics and Astronomy Education Research Group at UNC conducts research on the student learning experience, with goals focused on enhancing students’ conceptual understanding of the chosen topics in addition to improving scientific literacy and student attitudes toward science. The group members — Drs. Alice Churukian, Duane Deardorff, David Smith and Colin Wallace — are currently involved in two large course transformation projects, championing the incorporation of many research-based and research-validated teaching methods. This group of professors meets several times a week with the principal purpose of evaluating and assessing the student learning environment such that it promotes learning and understanding. At present, the group is largely focused on the transformation of the introductory physics and astronomy courses. In order to improve pedagogical practices, the team begins with a scientific approach to the goal — namely, understanding the subjects, gathering empirical data and controlling variables. In practical terms, the professors realize this step through student interviews. The professors draw up a precise framework of interviews to gather students’ reactions to specific circumstances in the courses that students are taking. During the interviews, students are asked to solve problems that elicit their conceptual understanding. The professors record the students’ answers as they explain how they would solve the task presented to them. They then ask that students think out loud, since this reveals the logic students go through in order to solve the problem. The interviews reveal a refined understanding of what subject matter students are struggling with. The data collected from these interviews is used to develop large-scale assessment questions, which in turn enable the methodical gathering of data for the research. Another way that the Physics and Astronomy Education Research Group

Figure 1. (Above) Dr. Alice Churukian interacts with students in an astronomy studio. (Below) Students work in the SCALE-UP physics classroom. Seating is arranged to promote group interaction. Photos courtesy of Thomas Cox, Physics and Astronomy Research, UNC-Chapel Hil 2014. gathers data is through pre-tests and post-tests administered in introductory courses. The professors give these tests anonymously at the beginning and end of each course. They are then able to compare the results and demonstrate how well each student mastered core concepts as well as how much they improved from the beginning to the end of the course. Dr. Deardorff points out that both of these methods are part of a “feedback loop,” which is a common process professors use to vevaluate the success of the

course. In addition, professors routinely use feedback from students to make modifications to the course that directly address students’ struggles. Feedback loops also involve numerous dialogues and conversations among faculty about what is working and what is not working in their respective experiences. After more clearly understanding the struggles that students are going through, the team of professors will move to the next step — assisting students in confronting those difficulties. “Among the difficulties students

physics

Illustration by Donna Li confront in solving a problem or understanding a concept are attitudes and beliefs about a subject,” says Dr. Wallace. This affects the nature of learning and should be dexterously exploited. He refers to these attitudes and beliefs as “intuition” that needs to be refined. “Students come to the classroom with intuitive beliefs about how the physical world works,” Dr. Wallace said. Sometimes their intuition is useful even when it is not verified. To exploit this situation, the professor uses guided elicitation by asking questions that prod students’ intuition. The goal of the questions is to plant the seed of curiosity and suggest that students confront their intuitive belief and verify whether it is correct. Another technique to help students learn efficiently is referred to by the terms “elicit, confront, resolve.” In this technique, the professors try to elicit the incorrect response in a question on the first attempt (for example, in a clicker question), then confront the deep misconception that students have and resolve the misconception. Dr. Deardorff says that the “best type of questions are ones where students will not all have

the same answer.” When this situation occurs, students experience cognitive dissonance and feel the need to re-examine their answer. To amplify the effectiveness of this method, students must be able to talk to their classmates. Discussion

“All careers are faced with different problems that are messy, and it is necessary to look at facts and weigh evidence to come up with a conclusion.” -Dr. Duane Deardorff with fellow students will enable them to learn through peer instruction and allow the correct thinking to rise to the surface. Dr. Deardorff believes that any time students are able to interact in a lecture is extremely beneficial to the learning process. Indeed, these are techniques that engage students. As such,

they help students actively grasp novel concepts. Furthermore, while students are interacting and actively exchanging ideas, professors are also able to evaluate how they grapple with resolving the problem. With these techniques and methods, professors try to change students from novice to expert problem solvers. While novice problem solvers focus on the immediate surface features of a problem (for example, the mechanical aspect of a box sliding down a ramp), expert problem solvers recognize the underlying concepts in a problem — they are able to see patterns and group problems of the same concepts together in order to solve them on a conceptual basis. Dr. Deardorff states that to be efficient problem solvers students need to learn how to face a problem that is ill-defined, weigh and examine the evidence and find a solution that makes sense based on that evidence. Even when they seem difficult, problems within the walls of a classroom are neatly presented; comparatively, as Dr. Deardorff explains, “all different careers are faced with different problems that are messy, and it is necessary to look at facts and weigh evidence to come up with a conclusion”. Learning how to solve problems in the classroom will prepare students for life outside of the classroom. With such far-reaching consequences, it is no surprise to learn that this research in pedagogy is funded by the National Science Foundation. UNC has been building on some of the work already done in physics education research. With funding, more graduate students can be hired, and there can be more assessments to develop empirical data and more presentations. If physics and astronomy seem redoubtable for many students at UNC, they will be relieved to know that there is an entire team of professors working tirelessly behind the scenes to help them understand these challenging subjects.

References

1. Interview with Duane Deardorff, Ph.D., David Smith, Ph.D., Colin Wallace, Ph.D., and Alice Churukian, Ph.D. 02/10/15.

Carolina Scientific

Illustration by Maura Hartzman

Google it UNDER PRESSURE Behavioral research improves search engine technology

BY KIMBERLY HII

information science

oogle only says it retrieved one million results for your search query. In reality, only about 300 of those search results are actually accessible to the average searcher, although most never click past the first page of results. People communicate their information need — what they are trying to find — to a search engine through what they enter into the search box, but they also make other choices during their search which provide information about what they are trying to find. At the Interactive Information Systems Lab, researchers in interactive information retrieval (IIR) study how people interact with search engines when looking for information. IIR is closely tied to human-computer interaction (HCI) and traditional information retrieval (IR), two well-established areas of research in computer and information science. Where HCI studies people for information, “If there are regulari- looking and traditional IR studies ties in how people are how search engines prosearching differently, cess information, IIR looks at how people use search we might be able to engines and what they design an interface to think about when searching. “[IIR research] hopes to support that.” improve the search experi-Dr. Diane Kelly ence — to improve people’s productivity [and] satisfaction when they look for information,”1 said Diane Kelly, a researcher at the Interactive Information Systems Lab at UNCChapel Hill. Search behavior is one of the topics of interest at the Interactive Information Systems Lab. “If there are regularities in how people are searching differently, we might be able to design an interface to support that,”1 Dr. Kelly said. To tackle this interest, the lab studies situations such as searching under time pressure and measures conditions of stress through physiological responses such as heart rate and sweating. However, people do not search the same way in a laboratory setting as they do in daily life. “In order to control as many [variables] as possible, we have to assign people search tasks,” Dr. Kelly said. “When [search study participants] are searching for something that’s not their own task, they might behave differently than if they were genuinely interested in the task.” To mitigate this, researchers in IIR generate search

tasks from topics likely to be interesting to participants. For instance, a study of query cost and search behavior asked users to run searches on the topics of wildlife extinction and abuses of e-mail.2 Search engines tailor search results according to the user’s location and search history among other factors, but Dr. Diane Kelly this ability to adapt goes both ways. When people have used a search engine for some time, they begin to adopt search behaviors that work well with it — possibly at their own expense. “[Searchers are] reacting to what the system is doing,” Dr. Kelly said. “The search engine can potentially exploit biases…and condition people to behave in ways that are beneficial to the search engine, but not necessarily to the person.” When using Google, many people stop searching long before they have finished looking through the many pages of results. This makes it possible for Google to report a lot more search results than it can actually show to the searcher. Recent developments in search technology have broadened the scope of IIR beyond studying people who use search engines at desktop computers. For instance, when people search on their mobile phones, they scroll less and spend longer looking at the results they click.1 Natural language processing is also used in natural language user interfaces, found in personal assistant apps such as Siri. When you type a question into the Google search box, the search engine recognizes it as one and makes an attempt to answer it. “People in IR were working on [spoken language retrieval] 20 years ago,” Dr. Kelly said. “The technology of the time could not sustain an interaction, but now people have conversations with their cellphones all the time. Technology has caught up with the idea.”

References

1. Interview with Diane Kelly, Ph.D. 05/02/15. 2. Azzopardi, L.; Kelly, D.; Brennan, K. How query costs affect search behavior. In SIGIR ’13, Proceedings of the 36th international ACM SIGIR conference on Research and development in information retrieval, Dublin, Ireland, July 28–Aug 1, 2013; ACM: New York, 2013.

psychology

By Aly Helms Photo by I should be Folding Laundry, CC-BY-2.0.

an scientists detect neurological damage or genetic Dr. Johns hypothesized that the disorders in infants by analyzing their cry? Believe it or cocaine treatment during pregnancy not, Dr. Josephine Johns and her team at the University was blocking or interfering with a of North Carolina at Chapel Hill’s Department of Psychiatry are critical hormone necessary for normal analyzing the cries of babies that have been exposed to co- early maternal response in the rodent, caine in utero. Studying the cries of infants can lend insight oxytocin, thereby resulting in higher into their bodily functioning and can serve as a marker for de- rates of infant neglect. The infant’s velopmental disorders. Moreover, a reliable method of study- ability to elicit care from a mother may ing the effects of drugs on a baby’s cry could lead to earlier be disrupted or blunted by cocaine ex- Dr. Josephine Johns treatment intervention. Dr. Johns’ research uses both human posure in utero and, when added to a and rodent models to assess not only the baby’s cry but also drug abusing mother’s diminished ability to respond, sets up the mother’s reaction. a potential situation for higher levels of neglect. This research began when Dr. Johns and her colleagues Ultimately, Dr. Johns’ research aims to understand how decided to use infant cries as a translational measure to as- cocaine affects a mother such that they do not respond norsess drug effects in both species. She investigated the devel- mally to infant cues and how prenatal exposure to cocaine opmental behavioral changes following cocaine exposure in affects the infant so that they may not produce these cues utero on rodents from infancy to adulthood. She soon be- normally. Dr. Johns’ current study compares the cries of both came interested in the maternal rodent and human babies that behavior as well since few inhave been exposed to cocaine The cry of a baby that has been vestigators were looking at this during pregnancy with those of important aspect of influence babies that were not exposed. exposed to drugs appears to on behavior and development This involves studying the cry’s differ from non-drug exposed of offspring. When she came to length, pitch, amplitude, utterUNC to study with Dr. Cort Pedand frequencies. The recries in several key ways: higher ances ersen in the Brain and Develsearch method was first conductfrequency, higher pitch and opment Research Center, she ed in a set of rat pups in a way believed the role of the mother that could be duplicated with turbulence. was critical in cases of infant human babies. The babies were neglect, and there were almost placed on a cold weighing scale no studies evaluating how cocaine affected mothers and their to induce crying, and the cry was recorded so that it could be important early interactions with their babies. later analyzed. Rat pups vocalize in ultrasonic waves which are “The studies that were being conducted on cocaine and not detectable to the human ear, but when slowed down can maternal-infant interactions were not systematic or thorough be heard. Analyzing infant cries is extremely time-consuming at that time,” Dr. Johns said. “We felt the biological aspects of and difficult, and it took several years to analyze the cry charhow cocaine might interfere with response to infants were an acteristics with the help of an expert in infant cry analyses, Dr. important aspect of drug related maternal neglect of infants.” Phillip Zeskind. The cry of a baby that has been exposed to

Carolina Scientific

Figure 1. The interaction between mothers and their young was first studied in rats. The mothers responded differently to the pups that had been exposed to cocaine during pregnancy, even if the mothers were not exposed. Photo by La Tarte au Citron, CC-BY-ND-2.0. drugs appears to differ from non-drug exposed cries in several key ways: higher frequency, higher pitch and turbulence. When looking just at the waveforms, which show the shape of the frequency levels, normal cries are more consistent and the cocaine cries have more turbulence. This increase of turbulence in cries is seen in both human infants and in the rat pups prenatally exposed to cocaine and represent the first translational study of this kind. Cocaine exposure during pregnancy affects not only the baby but also the mother and how she reacts to the child. To mothers, crying is the “biological siren” that their baby needs something. As the earliest form of communication between a mother and her baby, crying should be a way of bonding, but this is not always the case. Due to their distress, babies that have been exposed to cocaine often cry to the point that the mother cannot comfort them. In both the mother and the

psychology

infant, the drugs may affect their endocrine system, brain circuitry response, stress response, sensory interactions and behavior responses. Dr. Johns and her colleagues explore both sides of the maternal-infant equation. Dr. Johns sees promise for the future of this research, including behavioral therapy for the mothers or early infant intervention for neurobiological issues affecting their ability to elicit care and respond to mothers normally. Therapy for mothers to increase their awareness of the reason their babies may cry excessively is already being done in several trials. Dr. Johns notes the difficulty in finding human subjects who have used only a single drug such as cocaine, and thus the many control groups that are necessary to control for polydrug use. “It’s interesting because a lot of things can affect a cry, but if you control for those environmental factors in animals and still find that same cocaine effect, that indicates that it is probably not just something going on in the environment,” Dr. Johns said. “The use of a controlled animal model is very helpful to isolate biochemical changes and behavioral effects in translational studies. Ultimately our goal is to improve the outcome for the mothers and infants and to understand how drugs of abuse like cocaine affect the neurobiology and behavior of individuals.”

References

1. Interview with Dr. Josephine Johns, Ph.D. 2/11/15

Illustration by Ivy Somocurcio

psychology

The Brains Behind Psychiatric Disorder By Kennedi Briggs

our brain may be setting you up for psychiatric disorder. It is commonly understood that disorders such as Alzheimer’s disease and schizophrenia are genetic, but what is less common is the notion of how genetics affect brain development and the understanding of other mechanisms behind psychiatric disorder. For example, Alzheimer’s is a mental disorder that comes from the Dr. Rebecca d e g e n eration Knickmeyer of brain tissue. Rebecca Knickmeyer, a postdoctoral researcher in UNC-Chapel Hill’s psychology department, and her lab were the first to discover how genes related to Alzheimer’s affect the brain at birth. The Apolipoprotein E (APOE) gene is responsible for packaging and carrying cholesterol throughout the bloodstream.1 The APOE gene is polymorphic, meaning it varies throughout the population, thus two people with different genetic codes will produce different versions of the APOE product. Though its function is seemingly unrelated to psychiatric disorder, one variant of this gene, epsilon 4 (e4), has been linked to Alzheimer’s disease and brain changes in adults.1 The e4 variant alters volumes of tissue in the hippocampus and parahippocampus regions of the brain, which are associated with memory loss. Though data shows that children with the e4 variant do not show changes in memory loss and cognition, their levels of hippocampal tissue make them biologically vulnerable. This is because with age, brain tissue degenerates, and if there is less to start with due to the e4 variant, people may experience symptoms earlier on.2 Identifying genetic variants alone is not enough to pinpoint which genes will cause psychiatric disorder. As a result, Dr. Knickmeyer uses neuroimaging and Genome-Wide Association Study (GWAS) in toddlers and infants to identify telltale signs of mental disorder. GWAS is used to locate genes that have a specific impact on some biological function. It locates all of the variations in a DNA sequence, and near-

ly nine million of these can be discovered at a time. To narrow down the number of variants being tested, another population of people needs to be tested in order to locate variants that are statistically significant above a certain threshold. To identify telltale signs of schizophrenia and bipolar disorder, Dr. Knickmeyer studies children whose mother and father both have schizophrenia. She uses GWAS to identify single base-pair variants in the child inherited from the parents. From the GWAS, she then obtains a Summary Risk Score (SRS), which tells the researcher how likely it is that the variants in the child’s genome will cause them to develop schizo-

Illustration by Julianne Yuziuk 42

Carolina Scientific phrenia later on. Dr. Knickmeyer then deduces how these genes affect brain development in infants using neural imaging.2 Some types of neural imaging used in the study are resonance imaging to observe the structure and size of the brain, fusion tensor imaging to detect connections between regions of the brain and functional connectivity to analyze how blood flow changes in different regions of the brain. Studies done in Dr. Knickmeyer’s lab show that children who have a high SRS have differences in their amounts of grey matter, the part of the brain that is composed of cell bodies and supportWith this research ing cells. Though technique, psychiatric grey matter may be an important varidisorders can be ant in the study of schizophrenia, it is identified in people hypothesized that before the onset of the overall process of any symptoms, which brain development, allows earlier treatment as opposed to the shape or makeup of and a decrease in the brain at one parseverity of the disorder. ticular point in time, is even more important. Supporting these findings is work done by Megan Kovac, Psy.D., on behavioral issues and brain shape. She has found that it is not the end point of brain development that is most important, but rather the path it takes to get there. This is because “most brain functions arise from distributed neural networks”3 and every region has its own complex system of networks and neurotransmitters. Because of this, “relationships between brain size and function are the exception rather than the rule.”3 This is important because, contrary to what we see in Alzheimer’s, the size of the brain is not directly related to the function in most psychiatric disorders such as schizophrenia and bipolar disorder. “By the time schizophrenia manifests,

Figure 1. A neuroimaging scan. Different colors in the brain refer to amount of blood flow in different regions of the brain. Red indicates an increase in blood flow, or activity, in a particular region, while blue represents a decrease. Image by Nhutche, CC BY-SA 3.0.

psychology

Figure 2. This is the normal growth of gray matter in the brain from ages five to twenty. At age five children susceptible to schizophrenia will have more gray matter than the brain shown above. Image public domain. a lot of abnormal brain development has already occurred,”2 said Dr. Knickmeyer. Even more interesting than the genetic factors in psychiatric disorder are the environmental factors. People may believe that the main environmental factors in psychiatric disorders would include things like whether the baby was delivered by cesarean section, whether the mother smoked or even brain volume at birth. However, one of the most crucial factors is gender. Gender is both an environmental and genetic study in the sense that it encompasses everything from gender roles and how different genders are treated in society to things like sex hormones. Statistically, autism, attention deficit disorder and persistent antisocial behavior are more common in males. On the other hand, disorders with adolescent onset such as various eating disorders, anxiety and depression are more common in females. Some disorders are not linked to sex in their frequency, but instead in how or when they manifest. For example, males have an earlier age of Alzheimer’s onset because estrogen protects against it. Likewise, there is a spike in schizophrenia cases in post-menopausal women.2 The overall goal of genetic psychiatric research is to predict who may develop the disorder. Individual genes alone do not determine whether a psychiatric disorder will develop. However, with the combination of specific gene variations identified by GWAS and neuroimaging, we are able to get deeper into the mind — literally — of those who either have the disorder or are likely to contract it. With this research technique, psychiatric disorders can be identified in people before the onset of any symptoms, which allows earlier treatment and a decrease in severity of the disorder.

References

1. Genetics Home Reference. http://ghr.nlm.nih.gov/gene/ APOE (accessed February 13th, 2015). 2. Interview with Rebecca Knickmeyer, Ph. D. 02/03/15. 3. Kovac, Megan. M.A. Thesis, University of North Carolina at Chapel Hill, Chapel Hill, NC, 2011.

medicine

Title

Blood Donation: A+ Community Service BY RUKMINI DEVA

By Firstname Lastname

Image courtesy of US Air Force/Master Sgt. Linda C. Miller

ost people associate “community service” with volunteering in homeless shelters, raising funds for a charitable cause or tutoring English as a Second Language (ESL) students. Few students on campus may realize, however, that blood donation is perhaps one of the most direct forms of community service. Every day, donated blood components are administered to patients of all ages, including premature babies, oncology patients, trauma victims, organ transplant patients and surgery patients. According to the American Red Cross, someone in the United States is in dire need of blood once every two seconds, yet less than 10 percent of the U.S. population donates blood each year.1 The demand for blood continues to grow with the rise of specialist intensive care units, a growing elderly population and the ongoing needs of patients suffering certain diseases that were previously considered incurable. While whole blood donation is the most common type of donation, there is another option available for people who tend to get “woozy” after their blood is drawn. Volunteers can donate just their platelets — small cells that cause blood clots — rather than whole blood. Platelets are collected using a cell-separating machine that draws a small portion of blood (approximately one-fourth of a pint at a time) and returns the remaining blood components back into the bloodstream.2 Just one of these donations may provide up to three platelet doses for leukemia patients, which is equivalent to six whole blood donations (Figure 1).2 “Patients receiving platelet transfusions are often the

sickest people in the hospital, and our ability to effectively transfuse platelets to them is definitely and directly life-saving,” said Dr. Marshall Mazepa, professor of pathology and laboratory medicine and director of the UNC Health Care Blood Donation Center at UNC Hospitals. Because blood has a limited shelf life and is always needed by hospitals across the country, tremendous social marketing efforts Dr. Marshall Mazepa are necessary to ensure that donor blood supply exceeds demand. Much analysis has been done to understand the intrinsic and extrinsic motivations of blood donors and psychological factors that help to recruit new and returning donors. Some donors may be interested in the free pizza, movie tickets, snacks, T-shirts, volunteer hours and spalike pampering that the UNC Blood Donation Center provides. Others, however, are likely motivated by the prospect of providing help to ailing patients. For Dr. Mazepa, the direct impact that transfusion medicine has on patients is the most fulfilling aspect of his profession. Dr. Mazepa points out that there are times when “medicine intersects with other disciplines.” Certainly, the social marketing of blood donation necessitates an understanding of sociology, psychology and business principles. “It involves a set of skills which medical school did not

medicine

Carolina Scientific train me for, but it is an exciting challenge and the reality of modern medicine,” Dr. Mazepa said. The UNC Blood Donation Center encounters these challenges as it tries to make students aware of its existence on campus. “We want students to know that the Donor Center is here and to feel welcome. In college, it’s hard to feel like a big hospital is part of your campus or daily life, but this is truly a great place to make an impact,” Dr. Mazepa said. Transfusion medicine is a highly specialized branch of medicine that concerns blood components and their relation to the human body’s immune system. Physicians like Dr. Mazepa who are certified in transfusion medicine often serve as consultants for other physicians, providing expert advice on matters relating to hematology. Apart from working as the director of the UNC Blood Donation Center and seeing patients, Dr. Mazepa conducts clinical research on bleeding disorders as well as rare blood disorders such as thrombotic thrombocytopenic purpura (TTP). After specializing in blood diseases, Dr. Mazepa undertook further training in the field of blood banking, a field of medicine that deals with collecting, separating and storing blood products. Dr. Mazepa encourages pre-medical students searching for experiences in the field of medicine to explore transfusiology. “This is one way that students can directly impact patients, while learning how blood donation and transfusion medicine works,” Dr. Mazepa said. Most importantly, donating whole blood or blood components is a service to the community. There is currently no medical substitute for blood, which renders it extremely valuable for cancer patients, premature babies, trauma victims, organ transplant patients and those who have undergone surgery. For Dr. Mazepa and others in his field, blood donation is one of the greatest forms of community service.

1 platelet donation

patient

4-6 whole blood donations

Figure 1. Just one platelet donation can provide doses for three patients, while four to six whole blood donations are necessary to provide platelets for one patient. Figure by Erin Moore.

References

1. American Red Cross. Blood Facts and Statistics. http:// www.redcrossblood.org/learn-about-blood/blood-factsand-statistics (accessed February 14th, 2015). 2. American Red Cross. Platelet Donation. http://www.redcrossblood.org/donating-blood/types-donations/platelets (accessed February 14th, 2015). 3. Interview with Marshall Mazepa, M.D. 02/03/15.

Figure 2. The Blood Donation Center is located on the 3rd floor of the UNC Cancer Hospital. Image courtesy of UNC Healthcare.

Figure 3. Apheresis separates platelets from the rest of blood. Image courtesy of hsa.gov.

medicine

The instruments used during the simulation are identical to the ones used in real operations. Photo taken by Jeffrey Young.

a safer alternative

SURGICAL SIMULATION By Jeffrey Young

he operating room is not for the faint of heart. With lives constantly on the line, a surgeon must be well equipped to handle any possibility. A surgeonâ&#x20AC;&#x2122;s every move is carefully calculated and done with the utmost care. But when things do go wrong, a surgeon must act quickly and decisively to save the patient. As technology improves and these unforeseen complications happen less frequently, new surgeons must still be exposed to these rare possibilities and know how to deal with them. The field of surgical simulation is now emerging to fulfill this need. Dr. Richard Feins, a professor of surgery in the division of cardiothoracic surgery at UNC-Chapel Hill, is working to develop new methods of surgical simulation and the curriculum to teach it to prospective surgeons. The overall goal is to develop a simulation-based course of study for residents that would improve the quality of their training and thereby lead to more successful outcomes for future patients. Dr. Feins became inspired to research surgical simula-

Figure 1. The artificial pump used to make the heart beat. Photo taken by Jeffrey Young.

tion by considering how experts in other fields train to be successful. For instance, his son, a prospective Navy aviator, spent hours in a flight simulator during his training to develop his skills as a pilot. â&#x20AC;&#x153;He had crashed a thousand times before he had ever gotten into a real aircraft,â&#x20AC;? Dr. Feins said. He realized that this simulation aspect of pilot training could be applied to the way that surgeons are trained.1 Dr. Richard Feins This was nine years ago, and after doing some research, Dr. Feins found very little information or resources for simulating the complex cardiothoracic surgeries that residents would be expected to complete on a regular basis. He finally came across Dr. Paul Ramphal, who, along with his colleagues in Jamaica, had built a custom simulator for his students to practice on due to the lack of clinical material available. Dr. Feins contacted Dr. Ramphal and brought him to the United States to reconstruct his simulator. Since this pivotal moment, Dr. Feins has been working to develop procedures for performing different surgeries on this simulator. The simulator is a sophisticated mannequin to which different organs can be added depending on the type of procedure being simulated. For example, a heart can be placed in the simulator with balloons in each of its ventricles. Then, the instructors can load various computer programs that inflate the balloons in different patterns to replicate different types of heartbeats and abnormalities. Instructors can simulate many scenarios in this way,

Carolina Scientific some of which are very rare in a clinical setting, allowing the residents to practice these procedures. This is one of the great advantages of using a simulator. Instead of the traditional teaching methods, where residents work with real patients and instructors have no way to choose which types of operations they perform on a day-to-day basis, instructors can now hone in on certain operations and repeatedly run the same procedure. This repetition helps the resident put these techniques into muscle memory so their surgical moves will become instinctive. Using simulators also gives the instructor full control over the curriculum so they do not have to worry about what type of patient comes into the hospital or what complications may arise during surgery. “We can make good and bad things happen and tailor the experience for the student,” Dr. Feins said.1 Dr. Feins’ simulator uses animal organs that nearly mimic their human counterparts. The organs are obtained from pig farmers who would normally discard them. This makes simulation training a cost-efficient and humane endeavor. For Dr. Feins, using animal organs has sig“Instead of building nificantly simplified the a simulator for a development of these procedure, we built a simulations. “There was no need for us to try and patient you can do a reinvent something nalot of procedures on.” ture has1 already made,” he said. -Dr. Richard Feins Dr. Feins recalls that the most difficult aspect of the endeavor was preserving the organs and reanimating them once they were ready to be used. However, because of the widespread availability of these organs, there was plenty of material to practice on and thus perfect the techniques. For the first time, complex operations can be recreated in meaningful ways that the surgical community had once deemed impossible. Still, the simulations are not perfect. According to Dr. Feins, one aspect the simulators will never be able to recreate is the stress and weightiness a surgeon feels having the life of a patient in his or her hands. However, by preparing surgeons to adeptly handle the technical side of an operation, Dr. Feins hopes the simulations will allow the surgeon to better cope with the human aspect of the operation once a real patient is on the table. Medical students as well as undergraduates from UNC’s department of biomedical engineering help to develop new procedures for the simulators and new teaching curriculum. In this way, one simulator is serving as a modular interface where many different types of procedures can be developed and performed. “Instead of building a simulator for a procedure, we built a patient that you can do a lot of procedures on,” Dr. Feins explained.1 This is the underlying philosophy that drives Dr. Fein’s work. Surgical simulation training is quickly becoming an integral part of the training required for aspiring surgeons. With

medicine

Figure 1. (Top) Neal Murty, manager of the CLeAR Center where the simulation training takes place, prepares a pig heart inside the Ramphal simulator. Movie prop blood is used to increase the realism of the simulation. (Center) The simulator is ready for a procedure to begin. (Bottom) Another simulator at the CLeAR Center. A pig trachea can be placed in the mannequin so tracheotomies can be practiced. Photos taken by Jeffrey Young. new technologies being developed at such a rapid rate, simulators will continue to be integrated into the medical school curriculum. Simulation is now providing an alternative that is a safe, inexpensive way to better train surgeons.

References

1. Interview with Richard H. Feins, M.D. 1/30/15.

special feature

science major is

easy

By Avery McGuirt

Illustration by Maura Hartzman

ur science majors may be easier than we’d like evIt may come as a surprise, but German was widely exeryone to think. If you are within the 90 percent of pected to become the dominant language of science in the UNC-Chapel Hill science majors who grew up in the 1910s.3 However, World War I left behind widespread antiUnited States,1 then you belong to a privileged group of stu- German feelings, and laws were created which banned speakdents aided by decades of political changes — changes that ing, writing and teaching German in about half of US states. have pushed English to overwhelming dominance in scientific This corresponded with the formation of rule-making scienpublications. English appears to be here to stay as the world tific bodies like the International Union of Pure and Applied language of science, but as developing scientists and thinkers, Chemistry (IUPAC), which would exclude German as an official we must understand how this came to be and how this has af- language.4 These trends were even more pronounced after fected non-English-centric scientific World War II, which destroyed much communities. the infrastructure of Europe while The burdens for non-English of Scientific discovery and adthat of the United States, including its vancement was the domain of the educational and military systems at speakers and non-native Egyptian empire before pressures abroad, remained intact. English speakers to publish in home and from the expanding ancient Greek The end of World War II also empire forced a dispersion of culcoincided with the invention of the scientific fields are many. tural and scientific centers. The arcomputer. The first programming tistic and scientific dominance of the Greek territories and languages like Autocode, BASIC and FORTRAN were written language was then challenged violently by the Romans, and in English, with English commands and outputs.2 In this sense, so on. Though the lines have been redrawn and we’ve euphe- English was inextricably embedded into the framework of mized our empires, the last century has seen a massive shift what would become the most important medium for scienin intellectual and scientific power. A perfect storm of world tific exchange — the Internet. wars, a rapidly growing United States of America and the adIf this wasn’t enough to ensure the endurance of vent of digital technology set the stage for the steady growth English, the continuation of American and British imperial of English as the global language of science.2 systems through prodigious educational programs abroad

Carolina Scientific guaranteed that English was propelled to dominance not only from the west but from Asia, Africa and South America — essentially, former colonies and occupied territories. Various federal institutions such as the United States Agency for International Development (USAID), United States Information Agency (USIA), the Peace Corps and the Fulbright Program have spread American English and American pedagogy to classrooms around the globe. With more international students studying in the United States than US citizens studying abroad, the business of English education has become very profitable to the United States and its citizens. The citizens fill the very demand for English education that their government essentially invented.2 The end result of these factors is striking. In 1998, German sociolinguist Ulrich Ammon found that by 1996, 90.7 percent of all publications in the natural sciences and 82.5 percent of those in the humanities were in English.5 Going beyond simple publication rates, history has shown that when a language has dominance, other languages fail to reach a wide audience. In 1906, when English, German and French were equal in publication dominance, Russian botanist Mikhail Tsvet invented column chromatography to separate and study different chlorophyll pigments in plants.6 Chemists today would find it hard to imagine doing lab work without the principles of chromatography to analyze and collect products, but Tsvet’s findings were largely forgotten for about 30 years after his initial publication. He published only in Russian, and the scientific world paid no heed. It therefore seems that a scientist born and raised with the English language belongs to a privileged class, while those outside of the native Englishspeaking sphere play catch-up. Scott L. Montgomery, author of the recent book Does Science Need a Global Language, summarized the plight of the non-English speaker in a 2013 interview: Those without skill in this language, however excellent their research may be, are forced to inhabit a borderland, unable to participate at the core of their field and its highest levels. In this way, as with the bias problem, a global tongue can be impoverishing.7 The burdens for non-English speakers and non-native English speakers to publish in scientific fields are many. First, for the researcher with a weak working knowledge of English, a translation service may be a prerequisite for publication. The academic publishing company Elsevier offers translation services ranging from $682 for Portuguese to $810 for Arabic translations to English, based on a 3,000-word document.8 These are not insignificant sums of money to many researchers, especially since the locales most in need of the translation services tend to be poorer countries with less efficient educational infrastructure. For the researchers who write in English as a second or third language, there is also a significant and measurable burden. In 2011, researchers Karen Englander and David Hanauer studied a group of Mexican scientists who publish in English.9 They found that when English was a second language for a researcher, the individual experienced significantly more difficulty and anxiety during the publication process and was significantly more dissatisfied with the final product than a

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native English speaker. Enrich English Language Learning (ELL) is a studentrun English tutoring program at UNC for adults in the greater Chapel Hill area. Enrich illustrates the kind of work that the scientific community should be supporting to democratize the publication process. The program attracts people with diverse backgrounds and occupations, including researchers at UNC and Duke University. Kyeung Min Joo, a visiting scholar at Duke University’s department of radiation oncology, takes advantage of Enrich’s free tutoring every week. Dr. Joo has read and written papers almost exclusively in English, but he still pays a company to edit his work. This process is also necessary for Liping Wu, a visiting scholar from China in the School of Journalism and Communication at UNC. Wu, another Enrich attendee, says that in many ways the humanities are even harder fields to publish in for non-native English speakers because of the nuanced language. She says that “in hard science it is okay because the logic is the same, but social science is very difficult.”10 Native English speakers and others fortunate enough to have unlimited access to language education and translational sources are currently in a very important position, now that the dominance of English in science is a fact. We have to understand that our position of power is a manmade one, and that ignorance of the lingering stratification of scientists by language is hurting our peers.

References

1. UNC Office of the Registrar. DataMart Statistics. https:// regweb.isis.unc.edu/enrollment (accessed February 6th, 2014). 2. Kaplan, R. English — The Accidental Language of Science?. In The Dominance of English as a Language of Science; Ammon, U. Ed.; Mouton de Gruyter: Berlin/New York, 2001: pp 3-26. 3. Mair, C. Setting the scene. In Twentieth-Century English History, Variation and Standardization. Cambridge University Press: Cambridge, 2009; pp 8–11. 4. Porzucki, N. How did English Become the Language of Science? http://www.pri.org/stories/2014-10-06/how-didenglish-become-language-science (accessed February 1st, 2014). 5. Ammon, U. Ist Deutsch Noch Internationale Wissenschaftssprache? Englisch Auch Fur Die Lehre an den Deutschsprachigen Hochschulen. De Gruyter: New York/ Berlin, 1998. 6. Livengood, J. Stud. Hist. Philos. Sci. 2009, 40(1), 57–69. 7. Golden, S. Does Science Need a Global Language? https://www.insidehighered.com/news/2013/06/04/ interview-author-new-book-english-lingua-franca-science (accessed February 3rd, 2014). 8. Translation Service Prices. http://webshop.elsevier.com/ languageservices/translationservices/pages/pricing.html (accessed February 6th, 2014). 9. Hanauer, D.; Englander, K. Written Communication 2011, 28(4), 403–416. 10. Interview with Juliana Ritter, Liping Wu, and Kyeung Min Joo, MD, Ph.D. 02/23/2015.

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WORK IT. MAKE IT.

DO IT

with campus makerspaces By Matthew Leming

hat do prosthetics, molecular models and plastic monkeys have in common? Now, you can make any of them from a computer program. This idea of facilitating creativity is the drive behind University Libraries’ Kenan Makerspace, housed in the Kenan Science Library on the ground floor of Venable Hall. There, any student or professor can come in and use their wide array of tools for research, class projects or fun ideas. “We have several 3-D printers,

pelled forward by the advent of 3-D printing, the Makerspace initiative seeks to take these new tools and put them in the hands of students, researchers, and aspiring inventors. “We’re trying to bring together students from all backgrounds. Typically, shops that have machining equipment and tools like the Makerspaces in the Hanes Art Center and Murray Hall will have are specific to a department and can only be used by people within that department,” said Michelle Garst, the Program Manager of

made by someone at UNC that wants to submit their interpretation of the element.”3 Other projects include training classes to utilize several tools in the building of a MakNet sign and a life-size version of the game Operation to go on display in the Morehead Planetarium Gross Labs exhibit. Many students, additionally, have requested individual 3-D printed objects from the makerspace. “We got a lot of iPhone case requests, some of which are very interesting,” said Romito.1

from MakerBot to the new uPrint 3-D printer on loan from the campus makerspace, and a NextEngine 3-D scanner,” said David Romito, Biology Librarian at the Kenan Science Library. “We have Arduino and Raspberry Pi electronics development boards that we make available to classes and for checkout. A sewing machine and a soldering station will be ready for public use soon.”1 Inspired by the idea of a hackerspace — niche electronics workshops used by electrical engineers, computer programmers and tinkerers — and pro-

the Makerspace initiative. “The Maker movement at UNC is attempting to give open access to these tools and these resources to all students, faculty and staff.”2 The Kenan Makerspace is already home to a number of student projects. ”[A] current project is a large periodic table that will go in the Kenan Science Library,” said Kai Shin, President of MakNet, a student group dedicated to promoting and utilizing campus makerspaces. “This will be a community art project wherein each element will be

Photos by Matt Leming

“The Maker movement at UNC is attempting to give open access to these tools and these resources to all students, faculty and staff.” -Michelle Garst

Engaging the public with the Makerspace has largely taken place by showcasing hardware at campus events, such as TEDxUNC and Carolina Creates’ Create-a-thon. In the School of Journalism and Mass Communication, Dr. Spencer Barnes is offering courses on 3-D modeling. Additionally, the Kenan Makerspace is offering training workshops on 3-D printing, 3-D modeling, and the use of Arduino microcontrollers. “And sewing machines and soldering — those require training,” Garst added. Karen Erickson, the Director of the

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Photo by James Skinner Center of Literacy and Disability Studies in UNC’s department of allied health sciences, is one of the researchers utilizing the Kenan Makerspace for her own work. In a research project called Project CORE, Erickson is teaching school-aged students with cognitive and speech disabilities to communicate using symbols. In the study, most of these students will communicate using pictorial symbols. But, what about those students with impaired vision? “Enter 3-D printing!” said Erickson. “The students in our study who can’t see picture symbols will learn to use symbols that are printed in 3-D form. This is such an excellent solution in this research project because it allows us to create an initial set of symbols, study their impact with the students in our study and revise the design as needed in iterative cycles throughout the five-year project.”4 At the end of the study, Erickson’s group hopes to partner with the American Printing House for the Blind to standardize a set of 3-D symbols for students in need across the country. The Kenan Makerspace is a part of the wider initiative to incorporate hands-on, experiential education into student life. Currently, its managers, in collaboration with MakNet, are working to open two new makerspaces on campus, including one in the basement of the Hanes Art Center. “It will have a CNC router, laser cutter, 3-D printers and basic woodworking equipment. The plan is for the Hanes Art Center makerspace to open before the semester ends,” said Garst, adding, as she pointed upwards from her office in Venable, “The main space is going to be just up one floor

3-D printing in the Kenan Makerspace. (Left) A model of a mitotic spindle developed by the Biology Department’s Dr. Kerry Bloom. Photo courtesy of Dr. Bloom. (Right) A myoglobin protein with a heme molecule. Photo courtesy of Calvin Snyder. (Below) The Makerbot printing a 3-D elephant. Photo by Matthew Leming.

and across the hall in Murray Hall. That will be a 3,000 square foot makerspace that will have electronics, a metalworking shop, a woodworking shop, textiles, laser cutters and 3-D printers.”2 Commenting on the role of students and MakNet in opening these new spaces, Shin said, “We are really committed to making sure that these new facilities remain for the students, by the students.”3 In the long run, campus makerspaces will be used to give students a more hands-on, experiential education and provide a place for students, experts and tinkerers to gather, work and share their own knowledge. “There is

interest from across the disciplines, from archaeology to physics,” said Danianne Mizzy, Head of Kenan Science Information Services. “That’s a really important part of why it makes sense for there to be a campus makerspace.”1

References

1. Interview with Danianne Mizzy and David Romito. 02/19/15. 2. Interview with Michelle Garst. 03/09/15. 3. Email with Kai Shin. 03/11/15. 4. Email with Karen Erickson, Ph.D. 03/13/15.

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Creating a more diverse tomorrow scholarships support minority students in STEM BY JONATHAN SMITH

reating more diversity in the fields of science, technology, engineering and mathematics (STEM) is a process that will not occur overnight. Historically, many top programs and universities across the country have struggled to attract and retain talented members of underrepresented groups, especially African Americans and Latinos.1 Dr. Michael Summers, a chemistry professor at the University of Maryland, Baltimore County (UMBC), understands the magnitude of this problem and promotes training programs to increase diversity in scientific research. “Across the country, we have seen increases in the number of minority students that will earn a bachelor’s degree, but there have not been increases in the number of those going on to receive Ph.D.s and run research labs that help guide the government on how it should spend its research dollars,” Dr. Summers said.1 Many minority students are discouraged from pursuing studies and becoming leaders in STEM because of stereotypes, self-doubt and lack of support. STEM careers are perceived as too difficult in certain communities, and a discouraging academic environment or the absence of a mentor can lead stu-

“Across the country, we have seen increases in the number of minority students that will earn a bachelor’s degree, but there have not been increases in the number of those going on to receive Ph.D.s” -Dr. Michael Summers dents away from the fields. Challenging introductory classes during the first few years can cause academic struggles for even the highest-achieving high school students, and when students struggle to obtain decent grades competing alongside hundreds of declared pre-med students in large lecture halls, they feel overwhelmed and discouraged.1 “Data shows that a typical white male can figure it out after the first year and not necessarily be lost from the field of science,” Dr. Summers said. “But what we see is when high-achieving minority students and even women get into those early classes and struggle like

other people do, they tend to leave at a higher rate than do the majority kids.”1 Several universities have implemented programs to help and support minority students entering STEM fields. At the forefront of these efforts is the Meyerhoff Scholars Program that was created at UMBC over twenty-five years ago, and since its creation, the program has aided over eight hundred minority students. The goal of the program is to assemble high-achieving minority students into a scientific learning community where they can continually inspire each other, and by doing so, the Meyerhoff Program helps overcome the

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With these scholarship programs, UNC ultimately hopes to help minority students succeed and go on to become leaders in the scientific community. challenges minority students face during their first few years of their scientific undergraduate careers. Meyerhoff Scholars receive awards ranging in amounts from $5,000 to $22,000 per year for four years, as well as support resources and mentorship. The students also have the opportunity to participate in a summer bridge program that is designed to expose them to the difficulty of college course, so the adjustment period that causes many to flee from the field of science is shortened. Dr. Summers is a research mentor

THE MEYERHOFF PROGRAM: BY THE NUMBERS2

since the 26 years program began students graduated 900

of graduates 198 number with Ph.D.s

of graduates 107 number with M.D.s

for students in the program, and he emphasizes the value of placing students in research labs early on as a way to gain hands-on experience and turn their scientific dreams into reality. “As soon as they start their first class, they understand how difficult it will be for them to perform at a high level and how much work has to be put into it,” Dr. Summers said. “Once they are academically solid, we can get them in research labs and help them make connections so they can develop the self-

Figure 1. Dr. Michael Summers assists a Meyerhoff Scholar in his research lab at the University of Maryland Baltimore County. The Meyerhoff Program is now a model for many minority STEM programs across the country. Photo courtesy of Dr. Summers. identity of a scientist so that it is not something they would hope to be in ten or twenty years but something that they are now.”1 Since beginning his work with the Meyerhoff Program years ago, Dr. Summers has given presentations on its success at institutions across the country to encourage universities to implement similar programs.1 UNC-Chapel Hill was one such university, and in 2014, the Howard Hughes Medical Institution (HHMI) agreed to spend $7.75 million over the next five years to support a partnership between UMBC, UNC-Chapel Hill and Pennsylvania State University to strengthen their STEM minority scholarship programs. The Chancellor’s Science Scholars Program at UNC is designed using the Meyerhoff Program as its model. It aims to provide a pathway for success for minority students aspiring to become Ph.D. and MD/Ph.D. scientists. The program currently has its second cohort of students, and these students are working to recruit a third cohort. These students attended a summer bridge program and are provided mentorship and a $10,000 annual scholarship. The Ronald E. McNair Scholars Program at UNC

is another program designed to prepare high-achieving minority students for doctoral studies through involvement in research. With these programs, UNC ultimately hopes to help minority students succeed and go on to become leaders in the scientific community. “UNC has a group of very strong faculty, a top 10 chemistry department, and a really strong and respected medical school,” Dr. Summers said. “There is a large amount of research funding and surrounding technology companies that fund it, the best equipment to do research is available on the campus and North Carolina has a very diverse population. Those things should work together. UNC-Chapel Hill should be a leader in the country, producing African Americans who go on to be leaders, and the administration should be applauded for starting to make changes.”1

References

1. Interview with Michael Summers, Ph.D. 01/29/15. 2. UMBC Meyerhoff Scholars Program Results. http://meyerhoff.umbc.edu/ about/results/ (accessed March 6th, 2012).

Image by enzymlogic CC-BY-SA-2.0

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Enhancing an Education undergraduates pursue knowledge and develop skills in research labs BY KARA MARKER

ife-saving medication, innovative cancer treatments and stem cell therapy are all amazing discoveries that begin in a research laboratory. Many students do not realize the impact that research could have on their undergraduate careers. The unique opportunities at research-oriented universities provide invaluable experiences for undergraduates to enhance their studies in a variety of subjects. Every student should try research, whether as a potential career or as a way to gain a deeper understanding of scientific concepts. Each semester Dr. Gidi Shemer, Director of Undergraduate Research in Biology, holds an informational seminar on getting involved in undergraduate research at UNC-Chapel Hill. For incoming first-years and others unfamiliar with the research field, it can be ambiguous as to what research entails. During the seminar, Dr. Shemer explains how to find a lab that fits one’s interest, how to get class credit for doing research, availability and variety of projects going on in various departments, and opportunities available to those who pursue a career in research. For Brittany Simpson, who has worked in Dr. Tony Richardson’s microbiology lab since the summer of 2014, applying biological concepts in the lab has greatly increased her appreciation for active learning (Figure 1). While admitting lab work is a “rather large time commitment,” Simpson is particularly excited that she is able to “do the stuff you learn about in your biology classes.”1 Many students find lab work a helpful supplement while learning material in their science classes. Thus, involvement in research not only prepares students for their future but also enriches their current learning. One of the projects Simpson works on in the Richardson lab involves testing

Figure 1. Brittany Simpson pipettes a few microliters of broth-cultured S. aureus into a microcentrifuge tube in preparation for making diluted solutions of bacteria. Image courtesy of Brittany Simpson.

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Figure 2. (Left) A. thaliana plants, a model organism for meiotic recombination. Image courtesy of Savannah Nunnery. (Right) A typical microbiology lab bench: colonies growing, pipette ready and lab notebook open. Image by Kara Marker. the anti-microbial properties of cancer drugs on methicillinresistant Staphylococcus aureus (MRSA) (Figure 3). Simpson’s inspiration for pursuing research stemmed from her curiosity and uncertainty about post-graduation plans. Another undergraduate, Cory Breaux, joined a lab in the UNC Neuroscience Center as a work-study job. Over two years, Breaux developed skills in DNA sequencing, tissue preservation and animal care. Breaux appreciates his experience for “learning more about the academic scientific process and how researchers take ideas to reality.”2 In his statement, Breaux touches on the importance of engaging in research in addition to attending lectures for class. Application of ideas cannot be adequately learned and practiced through reading a textbook or flipping through a PowerPoint — rather, these connections can be made through conducting experiments and facing the tribulation of trial and error techniques. Like Simpson, Breaux recognizes and appreciates this enhancement of learning. Savannah Nunnery, a junior biology major preparing to become a physician’s assistant, decided to begin undergraduate research at UNC to take advantage of the incredible opportunities available to students at a major research university. She used the research directory available online to search for available student positions in genetics and molecular biology labs. Nunnery e-mailed a few professors explaining her background in biology and her interest in their lab’s research, and eventually joined Dr. Gregory Copenhaver’s lab in the biology department. Currently, Nunnery is in her second semester of research. She works with the plant model organism Arabidopsis thaliana and researches meiotic recombination and regulation (Figure 2). Specifically, Nunnery extracts DNA, runs polymerase chain reactions (PCR) and compares A. thaliana genomes. She mentioned initially learning about PCR and gel electrophoresis techniques in a genetics lecture before conducting these procedures on a daily basis in the lab. “It’s an entirely different way to think and learn about biology,” Nunnery

explained.3 “My daily research broadens concepts I learn in class from something I memorize to something I understand how to use.”3 As Nunnery explained, it is typical of a biology major to learn in class the steps of and draw the process of meiosis, the cell division process eukaryotes use to halve the number of chromosomes in a cell. It is not as typical to extract DNA from plants to directly assess their fertility qualities based on molecular tests of a specific protein involved in meiotic recombination, which is part of Nunnery’s project. Often, the skills that make a student successful while pursuing research go past acing lecture exams. Many students find a knack for navigating the scientific process and enjoy the potential to discover new metabolic pathways or enzymatic activities beyond the classic models learned in class. The ability to make a career out of growing knowledge is exciting for students who enjoy understanding how the world works. Many research opportunities also have clinical aspects, which might interest students who are interested in seeing the connection between research and medical applications. Simpson found value in active learning during her time in the lab, Breaux appreciated learning deeper about the scientific process and Nunnery enjoyed the synergistic experience of learning in lectures while conducting the experiments herself in lab. Ultimately, there is large value in a research career. A researcher is creative, innovative, patient and appreciative of discovering the truth. Students should take the opportunity to partake in research as an undergraduate if possible — for, no matter what career path they choose, they will always appreciate the depth of knowledge they gained from conducting their own research.

References

1. Interview with Brittany Simpson. 09/30/14. 2. Interview with Cory Breaux. 09/29/14. 3. Interview with Savannah Nunnery. 02/09/15.

“Research is formalized curiosity. It is poking and prying with a purpose.” -Zora Neale Hurston

Image by Ildar Sagdejev, [CC-BY-SA-3.0].

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Spring 2015 | Volume 7 | Issue 2

This publication was funded at least in part by Student Fees which were appropriated and dispersed by the Student Government at UNC-Chapel Hill.