Fall 2012 Issue

Carolina Scientific

Carolina

sc覺ent覺fic Fall 2012 | Volume 5 | Issue 1

The ability of phytoplankton like this one to sequester carbon from the atmosphere may be the key to reversing climate change. Full story on page 22.

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Carolina

sc覺entific 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 UNC-Chapel 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.

From the Editor: We are pleased to present the newest issue of Carolina Scientific. As the organization matures, we aim to make science engaging and accessible for readers by highlighting new and exciting research being conducted at UNC-Chapel Hill. This work has been made possible by our dedicated staff, interesting by the researchers whose work is featured here, and relevant by your desire to stay abreast of current research. Where else can you find articles about cognitive neuroscience, phytoplankton, and why ConnectCarolina is so slow? Enjoy!

on the cover

Executive Board Editor-in-Chief Managing Editor Associate Editor Associate Editor Design Editor Copy Editor Publicity Chair Fundraising Chair

Keith Funkhouser Kelly Speare Kelsey Ellis Sneha Rao Kati Moore Lauren Walls Amber Gautam Kandace Thomas

Contributors Staff Writers Hannah Aichelman Larry Zhou Sam Lucier Yurhee Lee Michael Parrish Matt Leming Sainath Asokan Erin Moore Corey Buhay Sam Resnick Hetail Lodaya Manning Jones Copy Staff Matthew Leming Hope Thomson Amelia Lorenzo Casey Clements Design Staff Madelyn Roycroft Paige Derouin Olivia Wayne Kelsey Ellis Calvary Diggs Erin Moore Hope Thomson

Image from the NOAA MESA Project

Phytoplankton, the base of the aquatic food web and our greatest source of oxygen, may also have the potential to reverse climate change. See page 22 for the full story.

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

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Carolina Scientific

contents 4

Don’t Hold Your Breath A new model for the periciliary brush layer has changed the way we think about lung health.

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Sainath Asokan

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Blame it on the Alcohol FASD is the leading preventable cause of mental disability and birth defects in the US—and it often goes undiagnosed.

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Plants are Picky When It Comes to Bacteria

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Cognitive neuroscience research sheds light on the genetic factors of addiction.

Putting Phytoplankton into Perspective Iron fertilization of Earth’s oceans may provide a means to reverse climate change.

Hannah Aichelman

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The Speed of the Web Researchers in computer science are working to build better, faster networks.

Matt Leming

Investigators untangle the complex relationships at play within a plant’s root environment.

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Sam Lucier

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Uncovering Addiction Michael Parrish

Finding a better way to predict damage from natural disasters could lead to changes in the insurance industry.

Hetali Lodaya

New imaging technology reveals a few sur-

Sam Resnick

Corey Buhay

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Understanding Your X prises about X chromosome inactivation.

Dynamic biomaterials have the potential to transform the way we do medicine.

Severe Weather and the Science of Risk

New silicon nanowires may be the missing piece of the puzzle for tomorrow’s solar panels.

Larry Zhou

Yurhee Lee

Shape-Shifting Materials

Nanoizing Solar Technology

Climbing to New Heights

The Promises of X-ray Fluorescence Molecular Imaging New imaging technologies have the potential to improve chemotherapy and other cancer treatments.

Rock climbing and geology meet to map the sheer face of Yosemite’s El Capitan.

Erin Moore

Manning Jones

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Don’t Hold Your Breath

A new model for the periciliary brush layer can help us understand how our lungs keep us healthy and lead to improved treatment of life-threatening disease.

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By Sainath Asokan

ven though we often take it for granted, it is amazing how many biological mechanisms in our body must function properly and in unison for us to be able to lead healthy and vigorous lives. One little-known example is the propulsion of mucus by cilia, which ensures healthiness of lungs and helps prevent various pulmonary diseases. Termed the mucus clearance model, this defense mechanism works to protect the lung airways from infectious and toxic agents. Its monumental importance is well illustrated by the terrible outcomes when this mechanism fails. Cystic fibrosis and chronic

obstructive pulmonary disease (COPD) are two such diseases that involve obstruction of airways due to buildup of mucus. More than 12 million adults in the US alone are diagnosed with COPD annually, while cystic fibrosis affects more than 30,000 children and adults (70,000 worldwide).2 According to the Centers for Disease Control and Prevention, chronic lower respiratory Dr. Michael disease was the third leading cause of Rubinstein death in 2010.1 In 2002, the Cystic Fibrosis Research and Treatment Center, in collaboration with faculty from the UNC departments of chemistry, applied mathematics, pharmacology, and physics and astronomy, decided to embark on the Virtual Lung Project, studying the mucus clearance model, how the mechanism is regulated, and eventually how it fails to function in disease.3 Also addressing the goals and intentions of the 2002 project, Dr. Michael Rubinstein in the department of chemistry, his post-doctoral student, Dr. Liheng Cai, and Dr. Brian Button of the Cystic Fibrosis Research and Treatment Center in the UNC School of Medicine made a recent breakthrough in the understanding of the structure of lung airways.

Their article, titled “A Periciliary Brush Promotes the Lung Health by Separating the Mucus Layer from Airway Epithelia”4 was featured on the cover of August’s Science issue. As Dr. Button notes, “The importance is in understanding how the biological system works and what is involved in maintaining normal mucus clearance. This finding allows us to understand the players in how the airway keeps itself healthy and why this system fails in disease.”3 The mucus clearance system on airway surfaces con-

Figure 1. A child suffering from cystic fibrosis needs assistance breathing. Cystic fibrosis occurs when mucus cannot be cleared from the lungs because the periciliary brush layer fails.

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Carolina Scientific sists of two main components. First, the top mucus layer works to trap inhaled particles and transport them out of the lungs through ciliary beating. Second, the periciliary layer (PCL) ensures proper ciliary beating and surface lubrication for movement of overlaying particles (Figure 2).4 The recent breakthrough provided insight into the makeup and structure of the PCL, suggesting that it is made up of macromolecular “brushes,” contrary to prior findings.

In previous pulmonary studies, the mucus clearance system has been represented by a gel-on-liquid model, consisting of a periciliary layer made of watery, low-viscosity liquid with an overlaying gel-like mucus layer.4 However, for Dr. Rubinstein and others, this model did not seem to fit their perspective of airway structure for two particular reasons. First, this model was not consistent with the system actually being Figure 3. Confirmed gel-on-brush model of the PCL. Repmade up of two distinct layers; if the PCL was indeed “watery”, resentation of gel-on-brush model with tethered mucins to mixing should occur between the PCL and the overlaying cilia and microvilli. Image courtesy of Dr. Brian Button et. gel. In other words, it was inexplicable why some macromol- al. Science. 2012, 337, 937-941. ecules in the mucus layer of various particle sizes (40-200 nm) could not penetrate the interciliary space in the PCL to form freezing techniques, electron microscopy, and vigorous washa single layer. Second, this model fails to explain why mucus ings were used to conclude that the mesh (macromolecular) clearance fails in disease, since it would actually be easier to size was between 20 and 40 nm, and that the layer consisted expel a “thinner” mucus layer out of the lungs as opposed to of very large macromolecules and membrane-spanning mua “thicker” two-layer mixture.3 As a result of these inconsisten- cins.4 To further identify these particles, immunohistochemiscies, UNC researchers agreed that the gel-on-liquid model had try studies, which use fluorescent selective antibodies to idento be incorrect in explaining airway structure, and proposed tify macromolecules, were conducted, allowing researchers to an alternative gel-on-brush model identify MUC1 and MUC4.3 Now that The propulsion of mucus by instead. they had confirmed that a “brush” ex In the gel-on-brush model, isted, the next step was to study and cilia ensures healthiness of the PCL consists of various mucins, or explore the various properties that high molecular-weight proteins, and lungs and helps prevent various could possibly aid understanding and large mucopolysaccharides that are development for applications. Since pulmonary diseases. tethered to cilia and microvilli conmesh size can describe important nected to the epithelial tissues (Figure 3). Dr. Rubinstein and physical properties such as permeability and osmotic prescollaborators hypothesized that this high concentration of sure, a certain dye technique using two probe molecules of tethered particles would cause intermolecular repulsion with- different sizes was used to quantify the PCL’s mesh size.3 in the PCL, allowing a distinct mucus layer to form above it and Dr. Michael Rubinstein pointed out that this study has mucus clearance to be carried out. In order to attain evidence various diagnostic implications: “It is comparable to when and confirm the existence of this macromolecular “brush,” you measure someone’s blood pressure to know how healthy their heart is; this way, you can maybe measure their mucus osmotic pressure to indicate how healthy their lungs are or determine if they are afflicted with diseases such as Cystic Fibrosis.”3 With further understanding of the disease state of ciliary immobility, Drs. Button, Rubinstein, and Cai all agree that possible development of treatment drugs targeted toward mucus clearance failure for cystic fibrosis and COPD will be made more feasible.

References

1. Leading causes of death. http://www.cdc.gov/nchs/ fastats/lcod.htm (accessed September 18, 2012) 2. Chronic Obstructive Pulmonary Disease http://report. nih.gov/nihfactsheets/ViewFactSheet.aspx?csid=77 (accessed September 18, 2012).

3. Interview with Brian Button, Ph.D., Michael Rubinstein, Ph.D., and Li-Heng Cai, Ph.D. 9/17/2012.

4. Button, B.; Cai, L-H.; Ehre, C.; Kesimer, M.; Hill, D-B.; Sheehan, J-K.; Boucher, R-C.; Rubinstein, M. Science 2012, 337, 937-941.

Figure 2. The cilia in the lungs are able to remove dangerous particles in healthy people because the periciliary layer ensures proper beating. Image courtesy of Charles Daghlian, Public Domain.

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Blame It on the

Alcohol

By Yurhee Lee

Fetal alcohol spectrum disorder

(FASD) is the leading known preventable cause of mental disability and birth defects in the United States. It affects more infants than autism, Down syndrome, cerebral palsy, cystic fibrosis, spina bifida and sudden infant death syndrome combined. FASD describes a range of birth defects that result from maternal alcohol use during pregnancy.1 While the most severe of these, fetal alcohol syndrome (FAS), is recognized by doctors through a common set of facial abnormalities, some individuals with other forms of FASD do not display these physical characteristics and remain undiagnosed.2

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t the Bowles Center for Alcohol Studies at UNC-Chapel Hill, Dr. Kathleen Sulik’s laboratory group is conducting research that can expand doctors’ abilities to diagnose alcohol-related birth defects.

FAS commonly manifests itself through three identifiable facial abnormalities: small head, shortened eye openings and a deficiency in the central groove of the upper lip.2 Doctors look for these phenotypes to diagnose infants and children with FAS. Researchers in Dr. Sulik’s lab, however, hypothesize that alcohol exposure at different times during pregnancy can result in different types of abnormalities that may be harder to diagnose. This can be a serious problem because even minor facial abnormalities caused by alcohol often indicate abnormalities in the brain.2 A recent study led by Dr. Robert Lipinski, a postdoctoral researcher in Dr. Sulik’s lab, investigated how the time of alcohol exposure affects facial and brain abnormalities. In the experiment, one group of mice was exposed acutely to alcohol at seven days into pregnancy, while another group

was exposed at eight and a half days.

Afterward, high-resolution magnetic resonance imaging (MRI) and dense surface modeling (DSM)-based shape analysis were used to visualize 3D structures of the mice fetuses’ faces and brains.3 The imaging analyses showed that there was a significant difference between the facial and neural features of the two mice groups. While the mice exposed at Dr. Kathleen Sulik seven days into gestation displayed the common features of FAS (a small head, shortened eye openings and a long, smooth upper lip), the mice exposed at eight and a half days showed a normal-sized head, less shortened eye openings, and a short lip with a groove. In addition, the early exposure group had characteristic FAS deficiencies in the median forebrain regions, while the later exposure group showed an inverse effect with a larger median forebrain.3

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Carolina Scientific

Figure 1. Left: A) On the computer, one of the scientists manually determined where the different parts of the brain were for the fetal mouse brain scan. B) This information was then used to generate 3D reconstructions of different parts of the brain by overlapping it with the brain scan. C) 3D reconstructions of the fetal mouse head were generated. D) Reducing the opacity of the model in C) allows the scientists to view the different parts of the brain in 3D. Right: Facial abnormalities based on stage-specific alcohol exposure. Images courtesy of Dr. Kathleen Sulik.

These results indicate that prenatal alcohol exposure pregnancy. The high school science curriculum includes a vircan indeed cause different types of facial abnormalities, de- tual experiment in which the detrimental effects of alcohol pending on the time of exposure. can be studied by exposing fish to Thus, it is clear that clinicians must “A lot of prevention needs to alcohol and 4 measuring the size of begin to look at the results of alcotheir brains. While the prevalence be done. Research isn’t done of FASD has serious effects on indihol exposure much more broadly.

The diagnosis of FASD can no longer just to talk to each other, but viduals across our nation, it is still rely on one set of common facial feapreventable. As Dr. Sulik so we can inform the public.” completely tures. The difficulty, however, is that states, “A lot of prevention needs to - Dr. Kathleen Sulik “at some stages, the face may look be done. Research isn’t done just to 3 perfectly fine, but the brain won’t.” talk to each other, but so we can inThe Sulik group’s research demonstrates the need to find the form the public.”4 Her group’s research and outreach efforts subtle, characteristic facial abnormalities that can help predict put us one step closer to the diagnosis and prevention of alcoassociated brain abnormalities and the resulting behavioral hol-related birth defects. phenotypes. Understanding how morphological changes in the brain are linked to specific behavior patterns can help psychologists and psychiatrists better treat and support patients IMAGING TECHNOLOGY of FASD.4 The Sulik lab’s efforts do not stop here. In addition to High-resolution MRI and DSM enabled uncovering the complexities of alcohol-related birth defects, the Sulik lab to create accurate 3D brain they are also involved in educating the public about the prevention of FASD. Dr. Sulik and her colleagues have developed and face reconstructions of fetal mice. The classroom curricula for middle school and high school science technology necessary to assess specimens students and DVD material for parenting classes that educate like fetal mice at a very high resolution has students about the effects of alcohol consumption during

only been developed within the last fifteen years. According to Dr. Sulik, “The high-res MRI and DSM let us look at the mouse brains in exquisite detail and find out where there may be particular parts that aren’t forming in the proper way.”4

References

1. National Organization on Fetal Alcohol Syndrome. www. nofas.org/faqs (accessed September 15th, 2012).

2. Interview with Robert Lipinski, Ph.D. 9/18/12.

3. Lipinski, R.J.; Hammond, P.; O’Leary-Moore, S.K.; Ament, J.J.; Pecevich, S.J.; Jiang, Y.; Budin, F.; Parnell, S.E.; Suttie, M.; Godin, E.A.; et al. PLOS ONE, 2012, 7, 1-10.

4. Interview with Kathleen K. Sulik, Ph.D. 9/18/12.

Figure 2. Infant with fetal alcohol syndrome. Image courtesy of Teresa Kellerman.

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Shape-Shifting Materials Biomaterials have the potential to transform the way we do medicine, one tiny boomerang at a time.

By Corey Buhay

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new breed of biomaterial has arisen, a breed of “smart materials. We were doing some rematerial” that can remember its shape, transform, and ally cool polyesters … and we realized even manipulate living cells. But have no fear—this is they were shape-memory,” she says no nightmare of science fiction, but a special type of poly- of the path that led her to her current mer developed and studied by Valerie Ashby, Ph.D. and her field.3 research group at UNC-Chapel Hill. “Shape-memory” is the Shape-memory is nothing new. descriptor used for a particular group of materials that can As a matter of fact, 3M, the company be molded from a certain shape, such as a boomerang, into that makes Post-it Notes, was lookanother shape, such as a horseshoe, and kept that way under ing into shape-memory polymers as certain conditions. However, when the temperature is raised a way to better their products’ adheDr. Valerie Ashby past a certain point, poof! All the horseshoes turn back into siveness, a property very much depenboomerangs1 (Figure 1). dent on the topography of a surface.4, 5 The new direction that In the future, this could lead to something as revolu- the Ashby group took was into biocompatible, biodegradable tionary as self-inflating vascular stents that would pop open materials—things you can put in the body that will remain for upon reaching body temperature a few months without any signifito prop up the walls of a collapsing cant allergic reaction or irritation artery (Figure 3). Robert Langer and dissolve over time when their and Andreas Lendlein have used job is done. Importantly, the mateshape-memory materials to create rials that the group has developed stitches that tighten in response to change shape right around body a particular temperature change temperature.1 to close up a wound 2 (Figure 2).

That means Ashby’s maDr. Ashby, however, has other apterials could one day be used for - Dr. Valerie Ashby plications in mind. time-elapsed release of medicine As a professor, research in the body or medical implants, group head, and department chair, Dr. Valerie Ashby has been like the aforementioned self-inflating stent. However, that involved in many aspects of biomaterials research. “This is the is far into the future. Right now, shape-memory polymer reway science works—you work on one thing and then some- search means that the living cells can be attached to shapething else happens … we did not set out to do shape-memory polymer materials, and previously unexplained aspects of es-

“This is the way science works— you work on one thing and then something else happens... we did not set out to do shapememory materials.”

Original

Temporary

Original

Return

Temporary

Return

Figure 1: Boomerang-shaped (left) and H-shaped (right) shape memory polymer particles. Images courtesy of Dr. Valerie Ashby.

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Carolina Scientific sential cell mechanisms can be studied in ways never before available. “There’s never been an opportunity to study cells on a dynamic surface—there just hasn’t been a surface that was biocompatible that you could switch at that temperature,” says Dr. Ashby.3 Previous to her work, many shape-memory materials could be induced to switch shapes, but it was very difficult to get the switch to ocFigure 2: Shape memory sutures that tighten into a cur at a temperature favorable knot when heated to 40°C. to cells. Even if the cells could Image courtesy of Science adhere to the material and survive, the switch would result in magazine. cell death if the transition temperature was too high or too low.3 “We’re operating in a pretty narrow window,” Ashby admits of the temperature. “It’s amazing that they switch as well as they do in that narrow window, but they do.”3 Creating a material that changes shape at just the right temperature isn’t the only hurdle. Observing the cells react to the change has also proven problematic. The film of cells has to fit into the instrument being used to analyze them, and the analysis has to be done at a carefully controlled temperature. “It’s not just a simple experiment. Everything is alive, it’s real-time measurements,” Ashby says. It is this dynamic aspect of the samples that complicates the process, but that changeability is the whole point.3 The very thing that makes the analysis difficult is precisely what makes the group’s research so novel: instead of static specimens, samples of moving, living cells can be examined while they react to the changes in their surroundings.

The cells actually cling to the surfaces they are on, so if that material stretches, so does the living cell.3 The Ashby group has started testing this by putting cells on the cross bars of tiny polymer shapes that resemble the letter H (Figure 1). “You have to get really creative.” Dr. Ashby laughs as she explains their original reason for making the shape, “We thought they were just cute, and we thought they’d never be used.”3 The group found the H’s to be very valuable—the cross bar provided a practical location to measure the stretch and observe the cells’ reactions to it.

By figuring out what kinds of pushes and pulls, and later what other types of topographical signals the cell responds to, the Ashby group hopes to answer some fundamental questions about how cells really work. For Dr. Ashby, this is a thrilling prospect. She was originally looking at stem cells to discover what exactly made them differentiate into one type of body cell over another—what cues make them turn into a bone cell rather than a liver cell, for example.1 “If we can figure out what the cues are, you can start to control differentiation into various specific avenues,” explains Ashby.3 Learning how cell surfaces react to different topographical cues is also important in understanding what sort of cues or cell behavior leads up to diseased states. If scientists know what changes to look for, they can diagnose a disease early and track it as it

Figure 3: The insertion and inflation of a vascular stent into a collapsing artery. Image courtesy of Science magazine. progresses. Knowing the exact mechanisms of cell reactions is also vital in designing medicines to stop or reverse those mechanisms that lead to diseased states. These are some of the long-term applications of Ashby’s research.

From paper product adhesives to modern medicine, shape-memory polymers have come a long way. Between their applications to new surgical procedures and to stem cell research, these shape-shifting materials have potential to enable scientists to make monumental new discoveries—certainly more monumental than stickier sticky notes.

References

1. Le, D. M.; Kulangara, K.; Adler, A. F.; Leong, K. W.; Ashby, V. S. Adv. Mater. 2011, 23(29), 3278-3283.

2. Lendlein, A.; Langer, R. Science. 2002, 296, 1673-1676.

3. Valerie Ashby, Ph.D. 10/25/12.

4. Sherman, A. A.; Bryan, W. J.; Galkiewicz, R. K.; Mazurek, M. H.; Starkey, J. R.; Winkler, W. J.; Zhang, H.; Olofson, J. M. 2011. U.S. Patent No. 7951319 B2. Washington, DC: U.S. Patent and Trademark Office.

5. Halford, B. “Sticky Notes: Serendipitous chemical discovery and a bright idea led to a new product that is ubiquitous.” Chemical and Engineering News. 2004, 82(14), 64.

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SEVERE WEATHER and the Science of Risk

By Hetali Lodaya

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hat we know as “weather” can be fairly straightforward. Defined as the condition of the atmosphere over a short period of time as seen through measures of temperature and moisture, we can predict weather with reasonable accuracy several days in advance. When these conditions lead to severe weather events, such as hurricanes, tornadoes, and floods, short term predictions allow us to plan for these events to minimize loss of property and life. Scientists have also developed sophisticated modeling techniques that give a better understanding of severe weather events that take place over the course months and years. Our ability to predict and understand severe weather, however, makes it no easier for the insurance industry to provide insurance against it. Understanding this paradox

Figure 1. Insurance companies must take into account the probability that severe weather incidents will occur when doing their own risk assessment.

Image courtesy of Leon Daly, Motovated Design & Analysis.

requires the science of risk assessment.

Professor Donald Hornstein, the Aubrey Brooks Professor of Law at the UNC Law School, works on linking longer-term weather predictions to our ability to provide financial insurance against weather-related losses. In 2008, the North Carolina General Assembly appointed him to a legislative study commission, to draft new laws addressing the availability of storm insurance, particularly in coastal areas. After the recommendations were signed into law in 2009, the North Carolina Insurance Commissioner appointed Professor Hornstein to the Board of Directors of the North Carolina “Beach Plan,” the state’s coastal wind insurance provider that the new legislation had reformed.

Professor Hornstein has been reappointed three times to the Beach Plan’s Board and has become increasingly recognized as an academic researcher on the economics, risk-analysis and assessment, and public policy of severeweather insurance.

Insurance for almost anything – health, car, home – depends on the principle of randomly distributed risks. This starts with the idea that bad things are not going to happen to everyone paying insurance. Looking at past trends and data, the insurer can determine with reasonable accuracy how many “bads” – hospital visits, car accidents, kitchen fires – are likely to happen in a year, and how much damage they will cause. This framework of combining potential for risk and estimated loss is the basis of risk assessment (Figure 1). Insurers use the results of this analysis to price plans to cover their costs while spreading the financial burden over everyone

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who is paying for insurance.

With a large enough risk pool, no one individual has to pay too much, and the insurer has sufficient reserves to cover all of the ex- Dr. Donald Hornstein pected losses.

This model breaks down, however, when the risks are not random, but correlated—risks that affect predictably large parts of a population. Extreme weather is a correlated risk, and this understanding is crucial to handling the damage that it causes. An entire town is unlikely to get into a car accident on the same day, but an entire town is likely to be affected by the same severe weather incident. If the residents all file damage claims, insurers have a problem. There’s still a risk pool—a group of people paying in to the insurance plans—but now everyone insured is filing for losses at the same time. Even worse, because insurance markets are typically localized by state, these all-at-once losses are not distributed across a national mix of high- and low-risks, but are instead concentrated on only a handful of state insurers. When Hurricane Andrew hit southern Florida in 1992, one dozen state insurers went bankrupt.1 It is not surprising, therefore, that in the 1960s private insurers withdrew altogether from the correlated risk of floods, calling such losses “ininsurable.”

This forced the federal government to create a subsidized system of flood

Carolina Scientific insurance called the National Flood Insurance Program (NFIP). Professor Hornstein’s overall research question examines the conditions under which the private free-market system for insurance might operate for remaining weatherrelated risks, forestalling the need for further government takeovers. This problem is hardly academic. According to Jane Lubchenco, Undersecretary of Oceans and Atmosphere at the National Oceanic and Atmospheric Administration (NOAA), “the number of extreme meteorological and hydrological events, defined in terms of economic and human impacts, has more than doubled over the past 20 years… The seemingly endless onslaught of floods, droughts, wildfires, windstorms, blizzards and tornadoes that have marked 2011 fit within an ongoing increase in the number of natural disasters recorded in the United States” (Figure 2). Insurance companies and states, especially those along the coast, are looking for more financially viable ways to deliver insurance.

One way in which Professor Hornstein’s research is unusual is the degree to which he allows undergraduate students at UNC to work on the project through summer research internships.

For the last five years, Professor Hornstein has taught a large undergraduate class on Environmental Law and Policy, ENST 350, and has accepted dozens of ENST 350 alumni as interns each summer. This past session, students collected data on state-run coastal insurance programs in Texas, Louisiana, Mississippi, Alabama, Florida, and South Carolina, as well as on international programs in the Caribbean, Bangladesh, South Africa, the Netherlands, and the Philippines.

In the fall of 2012, armed with the student research, Professor Hornstein and other members of the North Carolina Beach Plan interviewed the directors of many of these other programs. “In all cases,” Professor Hornstein states, “I was far and away among the best prepared people in the room because of the spoton research done by the UNC undergraduates.”

Professor Hornstein’s work has three general conclusions. The first is that over the last decade or so, private insurers have slowly begun to pull out of the weather-related market.1 Student

Figure 2. The National Oceanic and Atmospheric Administration notes that 2011 was a record year for extreme weather events and the damage they caused. Image courtesy of NOAA. researchers scoured both news articles and legal materials looking at flood and wind insurance to understand how insurers deal with increased costs. Insurers must get approval from regulatory agencies in any particular state to raise rates enough to fully cover the costs of all the losses they predict. If denied these rate increases, they abandon high-risk areas altogether or to offer only “hollowed out” coverage marked by large deductibles and lowered loss limits.

Second, Professor Hornstein studies how, with proper rates, even statebased storm insurance might be able to create long-term sustainable financial structures through private-market mechanisms such as international reinsurance and the tapping of equity markets through so-called “catastrophe bonds.” The North Carolina Beach Plan regularly engages in financial transactions on both of these fronts.

The study’s last conclusion is perhaps a bit more hopeful: insurers might be able to fundamentally alter the composition of their risk pools if more homes were built in a severe-weather-proof way. An insurer’s costs are dependent not just on the severity of the storm, but also on the construction of affected buildings. Better building can significantly decrease the structural and financial damage caused by severe weather.

Professor Hornstein is especially inter-

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ested in how storm-insurance entities can successfully incentivize these riskmitigation measures, such as retrofitting coastal homes to better withstand hurricane-force winds.

“In the end,” Professor Hornstein says, “this will be the most important contribution, actually improving the risk landscape by making human habitation more appropriate and resilient to turbulent weather, rather than simply finding dollars ‘from someone else’ to pay for repeat losses.” This chance for insurance companies to change the “impact” variable in their risk assessment is potentially a powerful way to cut costs.

The weather is a fickle thing – no matter how it changes in the coming years, the weather insurance industry will have to either adapt or disappear.

References

1. Hornstein, Donald. Personal interview. 25 Sept. 2012.

2. Romm, Joe. “NOAA Chief: U.S. Record of a Dozen Billion-Dollar Weather Disasters in One Year Is a Harbinger of Things to Come.” ThinkProgress.

7 Dec. 2011. <http://thinkprogress. org/climate/2011/12/07/384524/noaaus-sets-record-with-a-dozen-billiondollar-weather-disasters-in-oneyear/?mobile=nc>.

Bacteria have made their homes among the roots of plants for millions of years, but scientists are only starting to discover . . .

plants are picky

when it comes to

BY SAM LUCIER

BACTERIA

S

hoveling topsoil into plastic containers may not seem like the kind of groundbreaking scientific work that merits a publication in a high-level journal, but it was the first step for researchers in the lab of Dr. Jeff Dangl to publish in the prominent journal Nature. Bacteria can be found just about anywhere on Earth, and soil is loaded with them. Plants have evolved to form complex symbiotic relationships with microbes and do pretty well at distinguishing the good from the bad. In the Nature paper, the largest quantitative survey to date of plant-associated bacteria identified which types

Figure 1. Arabidopsis thaliana. Image courtesy of Alberto Salguero, [CC BY-SA-3.0].

of bacteria assemble in and around the roots of the plant Arabidopsis thaliana (Figures 1 and 2).

In plant roots, some bacteria are highly beneficial to the well-being of the plant. Beneficial bacteria play multiple roles, including helping the plant to absorb critical nutrients such as nitrogen and phosphorous, fighting off pathogenic bacteria, as well as priming Derek Lundberg, graduate the immune response of the student in the Dangl Lab. plant.1 They also directly influence plant growth by making plant hormones and promoting carbon sequestration.1, 2 Some of these beneficial bacteria colonize the rhizosphere, the area of soil directly surrounding the root, and others actually enter the plant root. Dangl explains: “Every shovelful of soil is different, and the microbial community is very diverse and extremely complicated. And everybody in that community is talking to each other using complex molecular signals”3 (Figure 3). Dangl and his team wanted to use genetic-based analysis to examine which types of bacteria evade Arabidopsis thaliana’s immune response by integrating with the plant and determining how the surrounding community is affected by the plant’s genes and the soil.

The first step of the research for this project, which started in 2009, was to collect soil from two plots, one near

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Carolina Scientific UNC-Chapel Hill at Mason Farm and another from a research station in Clayton, NC. The soil was then homogenized by removing visible plant matter, insects, etc. and crushing it to a fine consistency. More than 600 Arabidopsis thaliana plants with different genetic makeups were grown. Derek Lundberg, a graduate student in the Dangl lab, explained that they and others have found evidence that different Arabidopsis genotypes select different bacteria. This indicates a high level of selectivity and complex relationships formed between plants and bacteria, although soil type influenced bacterial communities more than the plant’s genetics did.

In order to actually identify which types of bacteria were present, the researchers focused on the 16S gene, which is so vital to basic cell processes, such as making protein, that it is present in all life forms. The gene is conserved in bacteria, but there are still enough DNA sequence differences that it is possible to classify bacteria into taxonomic groups. A technique called “next generation sequencing” was used to sequence thousands of 16S genes in every plant. Unfortunately, this technique is not precise enough tell you everything about a Figure 3. Soil type was found to have a large influence on bacterium. However, it can give you a good idea of what type the bacterial communities of the rhizosphere. Image courof bacteria is present in both the rhizosphere and the inter- tesy of Ondřej Zicha. nal root compartment of hundreds of plants. As a metaphor, this technique could identify an item of food as a hamburger, that, “It was clear from the beginning what the potential benbut it could not tell you the topefits to agriculture for this type pings, fat content, etc.

“If one can better understand how a of research are, and that our In order to be published work would be more complete plant chooses its microbial helpers, and convincing than existing in Nature, an article must have serious implications for science one could breed crop plants . . . [with] studies.” He explained that the and, often, a real world applicalab really wants to understand better yield with less pesticide and how the plant controls which tion of broad interest. Although Lundberg, the lead author on microbes are present and what fertilizer.” the paper, wasn’t originally exthose microbes provide in re- Derek Lundberg pecting such a high-level pubturn. Lundberg commented, “A lication because the work genplant prefers hosting one bacteerally confirms previously published observations, he stated rial group to another depending on its soil environment, and different genotypes of plants have different microbial preferences. If one can better understand how a plant chooses its microbial helpers, one could breed crop plants that make better choices about which microbes they hang out with, leading to better yield with less pesticide and fertilizer.”1 With the Nature publication, the Dangl lab and other groups around the world are one step closer to realizing these goals. Members of the Dangl lab are currently culturing real bacteria and working with more simplified microbial communities, building on knowledge from the deep survey of plants in natural soil to create even finer experimental tools.1 Look for many more developments to come from this lab.

References

Figure 2. The presence of bacteria (in green) on the surface of Arabidopsis roots can be seen using a fluorescent micrograph. Reprinted with permission from Macmillan Publishers Ltd: Nature, 2012.

1. Interview with Derek Lundberg. 9/12/12.

2. Lundberg, D.S.; Lebeis, S.L.; Paredes, S.H.; Yourstone, S.; Gehring, J.; Malfatti, S.; Tremblay, J.; Engelbrekston, A.; Kunin, V.; Glavina del Rio, T.; et al. Nature. 2012, 488, 86-90.

3. Roots and Microbes: Bringing a Complex Underground Ecology into the Lab. http://www.hhmi.org/news/dangl20120801.html (accessed September 9th, 2012).

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climbing to new

HEIGHTS

By Erin Moore

The iconic face of El Capitan is often considered a “rite of passage” among rock climbers, but it can also lend insight into the magmatic processes contributing to the formation of Earth’s crust. Combining his skills as a geologist and climber, geology graduate student Roger Putnam is undertaking a unique field research project to create a comprehensive digital map of El Capitan’s vertical face.

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Carolina Scientific

A

t first glance, it might seem that scientific research and ite, diorite or a hybrid between the two (Figure 1), including the sport of mountaineering make an unlikely pair. For El Capitan Granite, a smooth, fracture-free and hard type of geology graduate student Roger Putnam, however, granite that dominates the face. The combination of detailed rock climbing in the name of science is just another day on images that Putnam or other climbers take at specific locathe job. tions along multiple climbing routes (Figure 2) translates into Putnam spent this past summer scaling El Capitan, a a 0.1-meter scale map, extremely high resolution by geologic 3,300-foot granite monolith in Yosemite National Park, Cali- mapping standards. “Nowhere else on Earth is there an expofornia, gathering data for his master’s thesis. The aim of his sure as clean and as accessible as El Cap,” Putnam said. research is to create a comprehensive digital map of the geoThe inspiration for this project occurred four years ago logic features on El Capitan’s vertical face. Once complete, when Yosemite’s geologist Greg Stock, a geomorphologist, atPutnam hopes the map will benefit the four million that visit tempted to determine the source of a 3,600-year-old rockfall Yosemite each year. off El Capitan. The avalanche created a rock pile with three cu“Everyone can see it and learn from it: learn about gran- bic football fields worth of material.2 Upon closer observation, ite, learn about continental crust, learn about magma,” Put- Stock found that proportions of rock types in the pile did not nam said.1 correspond to the proportions Adequate geologic mapof rock types thought to be on ping requires a close-up view El Capitan’s face. Putnam’s map of rock formations to identify could account for these discrepconsistent characteristics that ancies. allow the rock type to be named “The hope is that by havand mapped. Accessing the rock ing a very detailed map of the becomes a challenge, however, face, that map will be able to be when the surface of interest is used by the people who want to vertical rather than horizontal. study the mechanics of rockfall,” - Roger Putnam “You need to be able to Putnam said. get there,” Putnam said. “All preThough not fully comvious attempts to map the face [of El Capitan] had been done plete, the El Capitan map has already produced results that by people sitting in the meadow below with field binoculars, could lend insight into the emplacement of El Cap’s granite. and there are obvious limitations to that method.”

For instance, Putnam’s research has shown that the uppermost That’s where climbing skills prove useful. “I can send a portion of the face contains mostly Taft granite, an extremely scale bar up the wall with a climber, who’s not even myself, hard type of granite composed almost entirely of quartz and who’s not even a geologist, and they can take photographs at feldspar. The Taft granite may have acted as a “cap” holding tothe belays with the scale bar, with the route name and the be- gether the other rock types on El Capitan. “We’re beginning to lay number on it,” Putnam said. “And I can then pinpoint that think that the shape of El Cap is a function of the actual types location and know exactly what’s there.” of granite it’s composed of,” Putnam said.

“What’s there” could be one of many types of granIn addition to taking photographs on his climbs, Put-

“

Everyone can see [the map] and learn from it: learn about continental crust, learn about magma.

Figure 1. A geologic analysis of rock types on a portion of the face of Yosemite’s El Capitan. Image courtesy of Roger Putnam.

Left: Putnam climbing El Capitan this past June. Image courtesy of Chris Gibbisch.

”

Figure 2. Example of a texture photo from a belay stance used to create Putnam’s geologic map of El Capitan. The board indicates the route and stance number location and serves as a scale for determining texture and grain size. Image courtesy of Roger Putnam.

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Figure 3. Geology graduate student Roger Putnam writes in his field notebook while climbing El Capitan this past summer to create a digital, comprehensive map of the granite monolith’s southeast vertical face. Image courtesy of Brad Potter. nam collected a total of 180 pounds of rock samples during his ascents. He will analyze these samples at UNC-Chapel Hill using X-ray fluorescence to determine the elemental compositions within each sample. This geochemical analysis may in turn help to settle a contentious issue in geologic circles— how to explain the magmatic processes that cowwwntributed to the formation of the granitic expanse of rock in the Sierra Nevada region of the western United States.

Around 100 million years ago, California’s west coast was a subduction zone, which occurs when one tectonic plate slides beneath another. Chains of volcanic systems characterized this subduction zone, and granite bodies such as El Capitan, called plutons, formed the roots of these volcanoes.

“The Sierra Nevada is like a fossilized footprint of where these volcanoes used to be,” Putnam said. “The hope is that by understanding the way by which the granite was emplaced, we’ll be able to understand more about the behavior of volcanoes.”

According to conventional geologic theory, granite plutons such as El Capitan formed when big blobs of magma rose into the Earth’s crust. If El Capitan were a giant magma chamber, then darker minerals with high melting temperatures such as iron would have crystallized first and settled to the bottom of the “big blob” when El Capitan’s granite was emplaced.

“What we’re looking for with these vertical transects is a progressive decrease in iron and magnesium and progressive increases in silicon,” Putnam said.

But chemical analysis of the rock samples collected by Putnam on his climbs has not shown this progression of minerals, suggesting that El Capitan’s granite may have been emplaced incrementally over time rather than cooling all at once as one large ascending molten blob.3,4 Putnam will return to Yosemite this fall to take more images and collect more samples on El Capitan. For him, that day cannot come soon enough.

“The face of El Cap is my favorite place on Earth … You walk up to the base of it, and it’s just so impossibly high, impossibly beautiful,” Putnam said. “It’s the ultimate inspiration.

That’s why I love it.”

References

1. Interview with Roger Putnam. 9/11/12.

2.Glazner, A. F.; Stock, G. M. The Walls Came Tumbling Down. In Geology Underfoot In Yosemite National Park; Mountain Press Publishing Company: Missoula, Montana, 2010; pp 103-110.

3.Glazner, A. F.; Bartley, J. M.; Coleman, D. S. GSA Today 2004, 14, 4-11.

4.Interview with Allen Glazner, Ph.D. 9/26/12.

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Nanoizing Solar Technology

Carolina Scientific

By Larry Zhou

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hen you see the blazing sun, do you ever wonder properties of solar cell technology. how much power it can produce? Every year the The Cahoon group works to imEarth receives enough energy from the sun to meet prove the material quality of nanowthe annual demand of the entire human population a little ires by tweaking various conditions over 20,000 times. Why doesn’t all our energy come from this during synthesis. Material quality is plentiful source? measured by the minority carrier lifeThe sun’s energy has not yet been utilized to its full po- time, how long an electron will stay tential because of one major obstacle: solar cell inefficiency. apart from a hole.2 As material quality Harvesting the output of the sun with current solar technolo- increases, the efficiency of nanowiregy is like trying to capture water from the Amazon River using based solar cells reaches or exceeds Dr. James Cahoon a cup. In order to develop a more efficient method of energy that of bulk-silicon-based solar cells.2 capture, Dr. James Cahoon and his newly formed group in the Furthermore, Dr. Cahoon believes that, “the key is to incorpochemistry department at UNC-Chapel Hill are exploring the rate other material. We can get around the limitations of silifundamental physics and chemistry behind solar cells. con.”2 Much like the alloying of metals, different atoms such as The most commonly used commercial solar cells are germanium can be added to these nanowires to gain the bencalled Generation I and are bulkefits of both silicon and the added “We haven’t seen the silicon based.2 While these solar cells element. may currently have the best efficienA process called advanced upper limit of what you can chemical cy-to-cost ratio, Cahoon says, “At this vapor deposition (CVD) achieve with nanowires.” point and time… we reached the is utilized to produce nanowires. In maximum point [of efficiency with the CVD process, silane gas (SiH4), a - Dr. James Cahoon bulk silicon solar cells].”2 Through source of silicon, is introduced onto their research, the Cahoon group hopes to discover methods a gold catalyst. At high temperatures, the gold and silicon to improve solar cells and go beyond this limiting point of ef- form a molten liquid called a eutectic drop.2 As more silane ficiency. gas is pumped into this reaction, the gold becomes superSolar cells generate energy when photons hit a semi- saturated with silicon. Supersaturation causes excess silicon conducting material, like silicon, causing electrons from the to be released from the molten gold. Instead of ejecting out silicon atoms to escape. This leaves behind a vacant electron a large mass of silicon, silicon nanowires are formed.2 During “hole” that is positively charged. The recombination of other the reaction, the nanowires can be doped with different gases electrons with the holes results in a net flow of electrons that to form the p-layer and n-layer. Diborane gas (B2H6) reacts to can be harnessed to generate electricity. A key piece of solar form the p-layer, and phosphine gas (PH3) forms the n-layer.2 cell technology is the p-n junction. A p-n junction is composed A nanowire-based p-n junction, thus, has a p-type core and a of an electron-rich n-layer and an electron-deficient p-layer. In n-type shell coating the core. a solar cell, the n-layer lies on top of the p-layer. When light By controlling the reactants and conditions used to synhits the n-layer and is absorbed by an atom, a free electron thesize nanowires, the Cahoon group hopes to create more can be emitted. This electron is attracted to the p-layer, which efficient solar cells. “We haven’t seen the upper limit on what is saturated with electron holes. The flow of electrons from the you can achieve with nanowires,” says Professor Cahoon.2 p-layer to the n-layer creates an electrical current that can be Maybe in the future, UNC can power its campus using efficient harnessed to generate power.2 nanowire-based solar cells.

Silicon nanowires, approximately 100 nm2 thick, are used to scale down the relatively large p-n junctions found References in bulk silicon cells to better understand the physics behind 1. Solar Energy Statistics. http://www.statisticbrain.com/ them. The small scale of nanowires enables the Cahoon group solar-energy-statistics/ (accessed September 21st, 2012). to study with great detail the inherent physical and chemical 2. Interview with James Cahoon, Ph.D. 9/21/12.

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Understanding Your X

By Sam Resnick

C

alico cats make great pets, but many people do not realize that they are also beautiful examples of a genetic phenomenon called Xchromosome inactivation. Their black, white and orange patches of fur are determined by the inactivation of one chromosome that harbors the gene for coat color. When the embryo contains around 100 cells, each cell will randomly block transcription from one X chromosome and maintain that transcriptionally silenced pattern in all daughter cells.

Calico cats happen to have their gene for coat color located on their X chromosome. This random process gives rise to unique color combinations in these animals, even among cats with the same genotype.

X-chromosome inactivation (XCI) is an event that occurs in all female mammals. Early in development, one X chromosome of a female is randomly silenced to preserve gene balance between males and females.1 Males have one X chromosome and one Y chromosome while females have two X chromosomes. XCI plays an integral part in red-green color blindness, and it is also why calico cats have such unique color

combinations, as both of these traits are linked to the X chromosome.

Dr. Terry Magnuson of UNC-Chapel Hillâ&#x20AC;&#x2122;s department of genetics became interested in the topic of XCI while studying the development of tissues in mice embryos. When Eed, the gene responsible for the development of many embryonic tissues, was mutated, Magnuson discovered an unexpected result: XCI never occurred in these embryos.

For the last ten years, the process of XCI has been a primary research concern of the Magnuson lab. XCI has proven to be a valuable model for the imprinting of chromosomes that do not involve sex determination. This is due to the fact that XCI is the most studied example of imprinting, a process where a chromosome or part of a chromosome is silenced based on the parent of origin.

Often, specific genes are always silenced on the paternal copy, while others are always silenced on the maternal copy. In these cases, a perfectly good copy of a gene inherited from one parent can be imprinted and not active, while a mutated gene inherited from the other parent can be expressed. Prader-Willi and Angelman syndromes are two examples

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of imprinting disorders where treatment has been positively affected by XCI investigation.

The cellâ&#x20AC;&#x2122;s method for choosing which X chromosome to inactivate is currently unknown and requires further

Figure 1. A calico cat showing patches of color due to X inactivation. Image courtesy of Tatiana Chessa [CC BY-SA 3.0].

Carolina Scientific

Figure 2. RNA-DNA FISH showing the location of the active X chromosome (Xa) and the inactive X chromosome (Xi). Image courtesy of B. Reinus and C. Shi [CC BY-SA 3.0]. research. The method of how a cell silences one of the X chromosomes is only slightly better understood. The prevailing theory as to how XCI occurs is that the chromosome that is randomly chosen will begin transcribing a long RNA.1 This long RNA Xist is crucial to recruiting protein to the inactivated X chromosome.1 Xist then surrounds the X chromosome that transcribed the RNA and stabilizes the inactivated chromosome.1 Proteins recruited by the Xist RNA alter the chromosome and provide a barrier to transcription machinery that could potentially transcribe RNA.1 While this evidence would lead one to think that Xist transcription is the hallmark of the

beginning of XCI, previous research by Dr. Sundeep Kalantry in the Magnuson lab suggests otherwise. In his 2009 Nature journal paper, Kalantry showed that XCI can begin independent of the Xist transcript, but that the Xist transcript is necessary for stabilizing the inactivated X chromosome.2 Dr. Mauro Calabrese, a postdoctoral fellow in the Magnuson lab, is building upon this research. He remarks, “X-linked gene-dosage abnormalities highlight why we study X-chromosome inactivation.” In addition to serving as a model for other imprinted diseases, X inactivation is crucial to diseases such as Triple X, Klinefelter and Turner syndromes. In Triple X and Klinefelter syndromes, there are more X chromosomes than normal, XXX and XXY respectively.

Despite these excess copies, the cell will accommodate and inactivate the appropriate number of X chromosomes.3 Without the cell’s ability to adjust the amount of XCI, huge gene-dosage issues would be present. Instead, females with Triple X syndrome appear normal, and males with Klinefelter syndrome are sterile and only show some female traits.

In the case of Turner syndrome, there is only one X chromosome in lieu of two X chromosomes, and the cells do not inactivate a sex-determining chromosome.

Using new high-throughput se-

quencing techniques, Dr. Calabrese worked to visualize the patterns of protein interaction with the genes on the inactive X chromosome.

In the first highresolution look Dr. Terry Magnuson at the inactivated X chromosome, Dr. Calabrese found data that suggests new information about the state of the inactive X in the cell.3 In the words of Dr. Calabrese, “High- Dr. Mauro Calabrese throughput sequencing allows us to understand how DNA on the inactive X chromosome is packaged in the nucleus.” His research suggests that the inactivated X chromosome does not show a completely silent epigenetic state as previously thought.3 Rather, this new research indicates that the inactivated X shows surprising characteristics of an active gene site.3 This means that transcription machinery has more access to the chromosome than expected.

While Dr. Calabrese’s discoveries seem to dispute the claims that XCI completely silences one X chromosome, they also advance what is known about XCI. Dr. Calabrese and Dr. Magnuson are continually working to research the topic of XCI and hope to one day better understand the process of XCI and the state of inactivated X chromosomes.

Striving for these goals will give us a better understanding of diseases that continually affect the human population.

References

Figure 3. The Xist RNA inactivation process. Image couresty of Dr. Terry Magnuson/ Nature Magazine.

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1. Sandrine Augui; Elphege P. Nora; Edith Heard. Nature Genetics. 2011. 12, 429-442 2. Sundeep Kalantry, Sonya Purushothaman, Randall Bryany Bowen, Johsua Starmer, Terry Magnuson.

Nature. 2009. 460, 647-651 3. Interview with Mauro Calabrese, Ph. D. 9/17/12

Uncovering addiction

By Michael Parrish

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ithout a doubt, addiction and substance abuse represent a devastating, pervasive problem for both individuals and society as a whole. According to the National Institute on Drug Abuse, substance abuse costs the country more than 600 billion dollars annually.1 While this statistic is astounding, it does not adequately convey the emotional effects of drug abuse and its effects on public safety.

Fortunately, investigators from a broad range of disciplines, including neuroscience and psychology, are working to design and test treatment plans that will help mitigate the effects of drug abuse. One such research group is the Cognition and Addiction Biopsychology lab (CABlab) of UNC-Chapel Hill led by Dr. Charlotte Boettiger, professor of psychology and principal investigator of the CABlab. Dr. Boettiger’s researchers use cognitive neuroscience tools, such as neuroimaging and genetic analysis, to explore the neurobiology of addiction. As stated by Dr. Boettiger, translational science labs such as the CABlab “lay the groundwork for testing

substance abuse therapies.”2 The CABlab is helping uncover specific behaviors and cognitive phenotypes associated with addiction. One of the lab’s most significant contributions to the field is discovering “factors that can interact with acute pharmacological agents.”1 By analyzing different genotypes and cognitive phenomena correlated with addiction, pharmaceutical companies and therapy designers will better understand which neural systems to target.Understanding how the brain interfaces with drugs is key to effectively implementing addiction research. The human brain has complex networks of neurons designed to reinforce naturally beneficial behaviors such as eating and drinking. However, drugs can take advantage of these life-sustaining motivational circuits by altering synaptic activity and global brain function. Simply put, synapses are the functional units for communication in the nervous system. To maintain healthy, adaptive behavior in humans, neurons and their synapses must perform controlled regulation of the chemical events during neurotransmission.

Understanding how the brain interfaces with drugs is key to effectively implementing addiction research.

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Carolina Scientific If any of the steps in neurotransmission are altered, behavioral and psychological consequences will emerge. Many prescription and recreational drugs function by exploiting a certain step in neurotransmission; for example, cocaine and several other drugs affect synaptic transmission by blocking reuptake of the neurotransmitter dopamine.

Dr. Charlotte Boettiger Understanding exactly how synapses are modulated by drug use and what specific regions of the reward circuitry are affected is the subject of intense research in neuroscience.

Most relevant to the CABlab’s research is the goal of correlating this neurobiological activity with specific addictive or impulsive behaviors.

Cognitive traits and behaviors are formed by a complex interaction of conditions and factors Christopher Smith such as age, sex, and genetics. Isolating certain factors that may cause particular individuals to be prone to addictive behaviors and impulsive decision making is a research goal of CABlab graduate student Christopher Smith. Smith was inspired to pursue a career in addiction research after experiencing the effects alcohol had on a family member.3 He specifically investigates the neurobiology associated with now-versus-later decision making. This “delay-discounting” behavior relates to choosing between immediate and delayed rewards. The discounting task used in the CABlab’s experiments focuses on subjects choosing

Calculating Cost

Estimated annual costs in the US, in billions1 Alcohol abuse: $235 Tobacco abuse: $193 Illicit drug abuse: $193 TOTAL: more than $600 between hypothetical monetary amounts with time delays.

An example is deciding between five dollars today or ten dollars in six months. Moreover, the process of delaying reward receipt can be conceptualized as being disrupted in addiction. For instance, a substance abuser may favor immediate positive effects of administering a drug now over the delayed reward of not being hungover as a result of drug use the following morning. As such, persons with previous diagnosis of an alcohol abuse disorder are more likely to value “now” over “later” in this discounting task.

Recently, Smith’s work led to an advance in the understanding of how age interacts with the COMT Val158Met genotype. His findings, published in the journal Psychopharmacology earlier this year, show that frontal dopamine signaling and delay discounting are modulated by both the COMT genotype and developmental changes from adolescence to young adulthood (Figure 1).4 The function of COMT under normal conditions is to degrade catecholamines, such as dopamine, in the prefrontal neural synapses. According to Smith’s article, the specific COMT genetic polymorphism studied in the CABlab “results in a fourfold reduction of COMT enzymatic activity.” Looking ahead, Smith says that he hopes to start using “the tools of magnetic resonance imaging (MRI) and ultimately positron emission tomography (PET) to better understand the neurobiology of now-versus-later decision making and the role of dopamine in this behavior.” 3 Chris Smith and Dr. Boettiger’s research is just one example of the many attempts being made to better understand the neurobiology of abnormal behaviors caused by addiction.

As a result of this type of scientific investigation, treatment plans will be optimized to account for differences in genotype and age so that more individuals around the globe can lead successful, fulfilling lives.

References

1. DrugFacts: Understanding Drug Abuse and Addiction. http://www.drugabuse.gov/publications/drugfacts/understanding-drug-abuse-addiction (accessed September 19th, 2012).

2. Interview with Charlotte A. Boettiger, Ph.D. 9/18/12.

3. Interview with Christopher T. Smith, 9/20/12.

4. Smith, C.T.; Boettiger, C.A. Psychopharmacology 2012, 222, 609-617.

Figure 1. This bar graph shows how the interaction between age and COMT genotype influences impulsive decision-making. The x-axis is labeled with the three genotypes associated with the COMT Val158Met polymorphism. The y-axis represents the ratio of impulsive choices to total task choices. Image courtesy of Christopher Smith.

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Putting Phytoplankton into

PERSPECTIVE

By Hannah Aichelman

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ake a deep breath. Now take an- process of taking in carbon dioxide from other. It is not often that we stop the atmosphere and turning it into simto think about where the air we ple sugars used for fuel. Fortunately for breathe comes from, but it is tiny ma- us, they release oxygen in the process. rine organisms called phytoplankton Dr. Marchetti is especially interested in that we have to thank for one of those one group of phytoplankton called diabreaths.1 Dr. Adrian Marchetti of UNC- toms.1 Chapel Hill’s department of marine sciDiatoms are an integral part of ences has dedicated his career to better primary production in today’s oceans. understanding the diversity of these These organisms account for one-fifth organisms and their of all photosyntheadaptations to the It is easy to forget how sis on Earth and are harsh environment the foundation of huge an impact such a oceanic food webs.1 of the open ocean.

Dr. Marchetti tiny organism has on Diatoms are dividdescribes his reed into two main the entire planet. search as a combicategories: centrics nation of fieldwork (Figure 1) and penand lab work. Fieldwork involves col- nates. The uniqueness and beauty of lecting phytoplankton samples from the diatoms is derived in part from their cell ocean, while back in the lab, the phy- walls, which are essentially made of glass toplankton are isolated and grown by (Figure 3).2 Dr. Marchetti is especially inmimicking their natural habitat. In this terested in what limits the growth of diway, Dr. Marchetti is able to control the atoms in the open ocean. While diatoms phytoplankton’s environment in order to have long been known to require nitrostudy how they adjust to various changes.1 Dr. Marchetti’s lab is home to several species of phytoplankton that live in large incubators where their natural habitat, including light concentrations, temperature and seawater conditions, is reproduced. These tiny organisms are helping Dr. Marchetti answer questions that could have important ramifications as climate change continues to alter the oceans.

Phytoplankton are free-floating, photosynthetic organisms found in both freshwater and seawater. They come in all shapes and sizes, are the base of the Figure 1. An example of a centric diaaquatic food web and are important for tom, one of the two main categories of biogeochemical cycles, especially the the diatoms, a type of phytoplankton. carbon cycle. Phytoplankton have the Image courtesy of Dr. Adrian Marability to photosynthesize, which is the chetti.

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gen and phosphorus, iron has recently been identified as an important limiting nutrient in the oceans and is the focus of the research being conducted in Dr. Marchetti’s lab. He uses cutting-edge molecular techniques to analyze diatom DNA and figure out how these organisms are able to adapt to iron limitation.

Dr. Marchetti studies diatom genomes, which are the blueprint of a cell, and the transcriptomes, which determine the parts of the genome that are turned on or off, to determine which genes are expressed under iron-limiting conditions.

The genomes of diatoms are incredibly diverse, as two diatoms might only share about half of their genes.

This diversity enables certain diatoms to cope with iron limitation better than others. Dr. Marchetti analyzes the genomes of such diatoms to Dr. Adrian Marchetti determine how they have adapted genetically to handle growing in iron-deprived oceans.1 Though iron is an essential component of the photosynthetic process, as well as many other metabolic pathways in phytoplankton, sources of iron to the ocean are few and far between. These sources include sporadic additions of windblown, iron-containing atmospheric dust and river runoff into coastal waters. As a result, 30 to 40 percent of the ocean is iron limited, meaning that organisms in these areas are constrained to grow with inadequate amounts of the element.2 Because iron plays such an essential role in photosynthesis, which requires carbon dioxide, there has been a significant amount of research in recent years to determine whether “fertilizing” the oceans with iron is a viable method to induce the growth of phytoplankton and, as a result, sequester carbon in the oceans. If scientists can induce phytoplankton growth in the oceans through fertilization, phytoplankton will photosynthesize more, take more carbon dioxide out of the atmosphere and then take that carbon with them when they die and sink to the bottom of the ocean.

Because carbon dioxide is a greenhouse

Carolina Scientific

Figure 2. This satellite image shows the extent of the phytoplankton bloom that resulted from iron fertilization in the North Pacific during the SERIES Iron Enrichment Experiment conducted in 2002. The dark areas are cloud cover, Alaska is located on the right side of the image, and the red patch in the bottom center of the image is the diatom bloom that resulted from the addition of iron. Image courtesy of Jim Gower, Institute of Ocean Sciences, Sidney BC. gas, some scientists believe that iron fertilization has the potential to combat global warming. Dr. Marchetti completed his doctoral studies in this field, examining the phytoplankton response during a large-scale iron fertilization study in the North Pacific Ocean (Figure 2).1 The concept of iron fertilization rests on the idea that adding iron to the oceans causes a shift in the phytoplankton population to being dominated by

diatoms. Diatoms are effective under these conditions because they are large phytoplankton, so they take in more carbon and then sink to the ocean floor quickly because of their heavy glass cell walls. While an exciting theory, iron fertilization of the oceans is controversial in practice. Dr. Marchetti argues, “There are too many unknowns that have not been resolved. The communities of organisms in the oceans are incredibly dynamic… the problem with doing this

on a large scale is that we can never predict how effective it will be.”1 In theory, diatoms have the potential to reverse climate change, which is why there is so much work being done to understand and perfect this process. Artificial fertilization of the oceans with iron shows promise, but the effective methods have not been found to accomplish this sort of large-scale manipulation of a natural process.

The study of marine phytoplankton has impacts that resound in many aspects of scientific research. With recent advances in genome sequencing, as well as implications in climate change, phytoplankton studies have the potential to answer today’s most pressing environmental questions. It is easy to forget how huge an impact such a tiny organism has on the entire planet.

Every deep breath we take serves as a reminder of the importance of understanding these awesome organisms and also protecting the habitat they call home.

References Figure 3. The cell walls of diatoms are made of silica, which results in beautiful displays when viewed under a microscope. Image courtesy of Dr. Adrian Marchetti.

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1. Interview with Adrian Marchetti, Ph.D. 9/11/2012.

2. Armbrust, E. V. Nature, 2009, 459, 185-192.

THE SPEED OF THE WEB RESEARCH ON TODAY’S NETWORKS CAN HELP IMPROVE THE SPEED OF TOMORROW’S.

By Matthew Leming

This map shows all the network connections that make up the World Wide Web. Image courtesy of The Opte Project [CC BY 2.5].

Y

ou pull out your laptop, open up a web browser, and click through to your homepage. What just happened? In a nutshell, your computer just used campus Wi-Fi to contact an outside server and request a packet. A packet is an encoded message containing all of the information you view on a web browser. They travel quickly, so quickly that a packet originating from across

campus or across the world would not lead to a noticeable difference for the user.

The department of computer science at UNC-Chapel Hill has an entire research group that analyzes the networks through which these packets travel: Distributed Real-Time Systems, or DiRT. One focus of DiRT is to analyze the thousands of HTTP packets that travel

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through a computer network and time the speed of servers as they send and receive different packets.

“What we do is measurement-based Dr. Kevin Jeffay research, and we are trying to understand how networks are

Carolina Scientific used so that we can make them better,” says Kevin Jeffay, PhD., a researcher in http://www.facebook.com/login.php DiRT1. Suppose you want to improve your local road system. One way to do 1. A user requests a webpage from their browser. this is to stop drivers and simply ask them how the roads could be improved.

A resource called login.php From a computer scientist’s perspecis requested via the HTTP protocol tive, this is the best way to improve neton the facebook.com server works: by systematically analyzing HTTP packets (the “drivers”) and determining 2. A server receives the request and begins the makeup of the server-client relationto send packets containing the information. ship, one can learn about and improve 3. The headers of these packets contain certain predefined fields: a computer network (the “road system”).

“I’m using the HTTP “The problem is, that’s illegal,” “Sending this protocol. No errors says Jeffay. “That’s called wiretapping. from sunny Palo so far!”

Alto, CA.” What we do is just capture the headers “Another Friday “This packet 1 on the packets.” Headers are a small HTTP/1.1 200 OK night spent on contains 6,905 Server: www.facebook.com part of an HTTP packet that list its port Facebook...” bytes of text Date: 19-OCT-2012 23:22:04 EST number and sequence number. A port in the HTML Content-length: 6905 language.” number says what the host is doing (for Content-type: text/html example, the HTTP protocol, commonly seen in web browsers, has port number 80), and a sequence number says how http://www.facebook.com/login.php many packages have gone between the server and the client thus far.

4. The packets are This seems like a small amount interpreted by the of information to research real combrowser, and the puter networks, but when combined webpage is with careful timing of the HTTP packets, displayed to the it provides a wealth of knowledge that user.

DiRT uses in statistical analysis of computer networks. The researchers of DiRT a normal speed, but the next, it would like a scientific process than what it is continue to develop be slower for no apparent reason. When today,” says Aikat.3 “Networking research methods of model- DiRT alerted IT of this problem, IT de- hasn’t been there as long as physics or ing these networks termined that they had misconfigured chemistry research… it largely doesn’t based on the infor- their servers. The student who based follow scientific process. We are working mation that is avail- his doctoral dissertation on that project towards making the process of networkable to the research used his research to start a company. ing research into a scientific process.” community.2 Using “Our overarching goals are to Regardless, it is indisputable that these models, they build better, faster networks,” says Aikat. research in network analysis will conDr. Jay Aikat are able to simulate “If you want to build something better, tinue to expand. Next time you open networks in the real world and find ways you want to evaluate what’s good and Google, Facebook, or ConnectCarolina, to improve them, detecting errors and bad about the existing networks.”3 What and say to yourself, “This is getting faster misconfigurations within one or many makes this research unique in computer and faster” or “I cannot believe how slow servers. science is its use of real world models. this is,” you can either condemn or thank For example, in 2009, DiRT decid- While computer science research usu- your friendly neighborhood network ed to analyze the output ally centers on topics that analyst. of the ConnectCarolina “Our overarching are reproduced in a lab servers. “In that proj- goals are to build setting, DiRT focuses on ect, we were analyzing analyzing and improving References better, faster the traffic from specific existing networks that 1. 1. Interview with Kevin Jeffay, PhD. servers and identifying networks.” are used every day. With 9/17/12 when the behavior was worldwide computer net- 2. Hernandez-Campos, F.; Jeffay, K.; - Dr. Jay Aikat outside of that expected works only appearing in Smith, F.D. Modeling and Generating range,” says Jay Aikat, PhD.3 When DiRT the last fifteen or twenty years, network TCP Application Workloads. 2007, analyzed the network connections of analysts are still working to perfect their <http://www.cs.unc.edu/Research/ the ConnectCarolina servers, they de- methods of research. dirt>. tected unusual patterns. One week, it “One of our major goals is to make 3. Interview with Jay Aikat, PhD. would process and send out packets at experimentation in networking more 9/26/12

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The Promises of X-ray Fluorescence Molecular Imaging New imaging technologies have the potential to allow doctors to better assess the location and concentration of drugs used in chemotherapy and other cancer treatments.

By Manning Jones Almost everyone today knows someone who has suffered from cancer.

Dr. Otto Zhou’s lab in the UNC-Chapel Hill department of physics researches cancer treatment in the hopes of lessening this burden. Their research focuses on a new radiation technology. According to Dr. Zhou, their recent work has been “aimed at developing a novel in vivo molecular imaging technique using X-ray fluorescence.”1 X-ray fluorescence molecular imaging (XRF) is a new technique which promises to allow doctors to produce better image analysis during application of chemotherapeutics and other chemicals used during image analysis for tumor treatment.2 The main principle behind XRF is that when elements are exposed to X-rays, they eject an electron as well as what is known as a K-α wave in the form of a photon. The emission of this K-α wave is a phenomenon known as Incident X-ray

Ejected electron

nucleus

K-α (resultant) fluorescent X-ray

Figure 1. View of platinum atom undergoing X-ray fluorescence. The incident X-ray causes an electron to absorb energy and be ejected. The deficient electron shell is filled by a higher-energy electron, causing it to give off energy in the form of a K- α fluorescent X-ray.

X-ray fluorescence3 (Figure 1). The energy released can be detected using a photon counter.2 Importantly, different elements have unique K-α wavelengths, so that they can be identified using XRF. The Zhou Lab has focused on determining the concentration of a specific chemical based on the amount of X-ray fluorescence occurring measured by the photon counter. Two of the main elements currently being studied are platinum and iodine. Platinum is found in Cisplatin, a common chemotherapeutic, and iodine is found in iohexol, a chemical used in creating images of tumors.2 When these drugs are injected into the patient’s body, they become concentrated at tumor sites.

XRF is currently being tested on mice in order to determine whether it can be used to identify the concentration of Cisplatin and iohexol. If this method proves to be effective, it may be considered for selecting drugs to use on human cancer patients.2 Being able to map the observed energies of the fluorescent X-rays emitted will enable scientists to identify not only the identity and concentration of the drug, but also its location in the body.

Dr. Zhou’s lab has constructed its own unique experimental setup to identify the fluorescence levels of iodine and platinum. Different concentrations of platinum and iodine were put inside a lead box in order to isolate the experiment from other radiation.2 From above the box, a thin beam of X-rays released energy was directed at the solutions.

Once they began to fluoresce, a photon counter inside the box recorded the amount of photons emitted at each energy level from the samples. Using this data, they were able to confirm the relationship between the concentrations of iodine and platinum and the emission

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Dr. Otto Zhou energies. In the future, the lab looks to collect more fluorescence data from different chemicals related to cancer treatment.

Being able to locate and identify the concentrations of chemotherapeutics has the potential to further enhance cancer treatment. At the moment, this work “is a pilot project funded by the National Cancer Institute through the Center for Cancer Nanotechnology Excellence,” says Dr. Zhou.1 Currently, scientists in the lab are discussing the possibility of using XRF directly on humans instead of lab mice. However, this is a goal that will likely take a long time to achieve. For now, the lab is aiming to more fully understand the relationship between drug concentration and XRF for a variety of different cancer-relevant chemicals. They hope to see XRF put to use so that doctors can more effectively choose drugs to give to patients, with the hope of eventually increasing survival rates.2

References

1. Email interview with Otto Zhou, Ph.D. 04/03/12.

2. Interview with Pavel Chtcheprov.

10/05/12.

3. Cao, G.; Lu, J.; Zhou, O. X-ray fluorescence molecular imaging with high sensitivity: feasibility study in phantoms. Medical Imaging 2012.

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“For science is more than the search for truth, more than a challenging game, more than a profession. It is a life that a diversity of people lead together, in the closest proximity, a school for social living. We are members one of another.”

- Oliver Wendell Holmes, Sr.

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

Carolina

scıentıfic Fall 2012 | Volume 5 | Issue 1

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

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