Fall 2008 Issue

carolina

sc1ent1fic Fall 2008

Undergraduate Magazine

UNC-Chapel Hill

Issue I, Volume I

Carolina Scientific

From the Editors To our readers:   As undergraduates who have been involved in research since high school, we understand and recognize the importance of research as the source of new and exciting scientific knowledge.

And who says that undergraduates cannot be involved in research?

With UNC as one of the best public research institutions in the nation, we hope that this publication will help other undergraduate students learn about and become involved in the many research opportunities in labs across this campus. Enjoy!

~Ann, Adele, and Lenny

Staff Writers Prashant Angara Elizabeth Bergen Kelly Bleaking Natalia Davila Lenny Evans Rebecca Holmes Alia Khan Mary La Ann Liu Adrian Pringle Rebecca Searles

Guest Writer David McInnes

~Adele Ricciardi is a sophomore majoring in Biochemistry and Biology.

~Lenny Evans is a sophomore majoring in Physics and Math.

~Ann Liu is a sophomore majoring in Biochemistry and Business.

For more information, please email us at: carolina_scientific@unc.edu or visit us online at: http://studentorgs.unc.edu/ uncsci

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-CH. 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-CH, and hopes to educate and inform readers while promoting interest in science and research.

Fall 2008, Volume I Issue I

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Carolina Scientific

Contents 4

Reconstructing Factors Influencing Higher Incidence of Female ACL Injury Adrian Pringle

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Gamma Ray Bursts: Chasing the Biggest Explosions in the Universe Rebecca Holmes

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Nature’s Drawing Board: How Natural Products Aid in Drug Discovery & Synthesis Mary La

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Magnetoreception in Sea Turtle Navigation Rebecca Searles

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Fantastic Neutrinos and Where to Find Them Lenny Evans

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The Development of Synthetic Heparin Prashant Angara

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Autoimmunity: How Defense Mechanisms Can Hurt Our Bodies David McInnes

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Reproductive Biology & Behavioral Neuroecology: The Sockman Lab Elizabeth Bergen

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Yes to NO: UNC Researcher Explores Molecule for Biomedical Advances Natalia Davila

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Physics Tips for Living a Healthy and Happy Life at UNC Kelly Bleaking

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SURF: Cambodian Drinking Water Alia Khan

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Undergraduate Summer Research Spotlights Featuring Brittany Fotsch and Lalitha Kunduru 3

Fall 2008, Volume I Issue I

Carolina Scientific

Reconstructing Factors Influencing Higher Incidence of Female ACL Injury Adrian Pringle, Staff Writer

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fter he was tackled following a punt return, Brandon Tate limped off the field. Bobby Frazor limped off the court after attempting to secure the basketball and landing awkwardly. The diagnosis for both athletes was a torn anterior cruciate ligament (ACL). During the past semester, about eight Lady Tarheel athletes suffered either a partial or complete ACL tear [1]. The major difference between male and female ACL injuries is that female ACL injuries often occur in the absence of physical contact.

Herein lies the problem.

Some coaches have taken precautions to insure the safety of their athletes [2]. These precautions range from modifying the strength and conditioning program to re-teaching the vintage jump-stop move to their players [1]. In general, ACL injuries are gruesome to witness.

The performance of teammates can become severely diminished as they are constantly wondering if they will be injured next. The well-being of athletes and the skyrocketing costs of healthcare, serve as catalysts propelling research designed to reverse this trend [3].

Structurally, the knee is an unstable joint. This instability is mostly due to the fact that the femur does not fit well into the pocket created by the tibia. The knee joint is essentially held together by a

Fall 2008, Volume I Issue I

network of muscles and ligaments.

David Bell, a doctoral candidate working in The Sports Research Laboratory at UNC, focused on the interaction between the hamstrings and the ACL. ACL rupture is due to excessive anterior tibial translation, movement of the tibia relative to the femur. The hamstrings are theorized

females [2].

Male and female subjects were used in a study to determine whether reproductive hormonal changes negatively affect hamstring stiffness. Test subjects had no history of previous ACL injury and were physically active. Female subjects exhibited normal menstrual Structure of the Knee cycles that were unaltered by contraceptives. Each female subject was tested three days after menses and again at ovulation.

Menses marks the point of lowest concentration of estrogen in the female body, while ovulation marks the opposite [2].

By using these specific biological markers, researchers were able to create a range of low influence of estrogen to high influence of estrogen. to protect the ACL by preventing Across the twenty-eight to thirty this motion. ACL injury commonly days of a normal menstrual cycle, results from direct trauma to the the concentrations of estrogen, knee joint. Also, muscle imbalances progesterone, and luteinizing within the hamstrings or quadriceps hormones fluctuate in the female due to sport specific training bloodstream [2]. These hormonal regimens can culminate in ACL changes, along with estrogen injury. Together or apart, these receptors on the female ACL, are anomalies can result in excessive one of the proposed reasons why anterior tibial translation. When females are more prone to ACL a ligament’s elastic properties injury [1,6,8]. While the primary are exceeded, the ligament can reproductive hormone of the rupture. However, new research has male is testosterone, estrogen and indicated that female reproductive progesterone are present in trace hormones may partially explain amounts. Intriguingly enough, the increased incidence of injury to the male ACL is immune to the

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Carolina Scientific influence of estrogen because it lacks estrogen receptors [1].

Researchers found that estrogen levels and hamstring stiffness were negatively correlated. A negative correlation implies that increased blood concentration of estrogen results in decreased muscle stiffness [1]. Therefore, females have a less stiff muscle. A less stiff muscle could cause an entire joint to operate improperly [5]. Previous research has suggested that estrogen is responsible for decreasing the collagen content within connective tissue. Decreased collagen content could result in a less stiff muscle, forcing it to provide inadequate support to the joint [4]. The lack of proper joint support due to decreased muscle stiffness and collagen content may be reasons why females are more prone to non-contact ACL injuries.

Contemporary female athletes are bigger, stronger, and more athletic than their peers from previous generations.

This increased athleticism requires female athletes’ muscles to exert greater force on the bones to which they are attached. Rate of force production and time to 50% peak force data gathered by researchers might also be influenced by hormones. Rate of force production corresponds to how quickly a muscle can produce force, while time to 50% represents the split second timing to react and prevent injury. Estrogen and rate of force production yielded a negative correlation. However, no correlation existed between time to 50% peak force and estrogen. Instead, there is a negative correlation between time to 50% peak force and testosterone [1]. In the case of the knee joint, the quicker a supporting muscle can produce force, the quicker that muscle can correct

for joint misalignment and prevent injury [2]. Females have lower testosterone concentrations within their bloodstreams and it takes them longer to reach 50% peak force.

Together, the negative correlation given for rate of force production and the negative correlation for time to 50% peak force, indicate possible explanations for the prevalence of non-contact ACL injuries suffered by female athletes [1].

Electrochemical delay (EMD) is the time interval between the initiation of electrical activity and force production during skeletal muscle contraction. Researchers found that there is no correlation between estrogen and EMD. A short EMD time corresponds to efficient interpretation of electrical activity by a given muscle. Theoretically, stiffer muscles have a shorter lag time between electrical signal and force production. Males generally have a shorter EMD time than females as a result. A longer lag time causes a muscle to react slower than required and may compromise joint stability [1]. Under these circumstances, female athletes would face an increased likelihood of injury.

Researchers found correlations between concentration of estrogen and testosterone in relation to muscle stiffness, time to 50%, and rate of force production. These correlations suggest that estrogen could be responsible for rendering a muscle less stiff [1]. Hormonal fluctuations could prove detrimental by affecting the ability of the knee joint to respond to increased force placed upon it [5]. Thus, consensus can be drawn that the elevated estrogen levels of females could be responsible for creating conditions in which their knee joints are not as stable as those of their male peers

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[7]. This induced instability could be one of the reasons why a female ACL injury often occurs in the absence of contact.

~Adrian Pringle‘10 is an Exercise and Sports Science major.

References

1. Liu S.H. et al. (1996). Primary immunolocalization of estrogen and progesterone target cells in the human anterior cruciate ligament. J Orthop Res. 14, 526-533.

2. Bell, D. R. (2006). The Effect of Menstrual Cycle Phase on Hamstring Extensibility and Muscle Stiffness.

3. Blackburn, J.T. (2004). Sex comparison of extensibility, passive, and active stiffness, of the knee flexors.

Clinical Biomechanics. 19, 36-43.

4. Agel, J., Bershadsky, B., Arendt E.A. (2006). Hormonal therapy: ACL and ankle injury. Med Sci Sports Exerc. 38, 7-12.

5. Salmon, L. et al. (2006). Long-term outcomes of Endoscopic Anterior Cruciate Ligament Reconstruction With Patellar Tendon Autograft. Am J Sports Med. 34, 721-732.

6. Wojitys, E.M. et al. (2002). The effect of the menstrual cycle on anterior cruciate ligament injuries in women as determined by hormone levels. Am J Sports Med. 30, 182-188.

7. Interview with D. R. Bell, MEd, ATC, PES 11/04/2008 8. Fischer G.M., Swain, M.L. (1977).

Effect of sex hormones on blood pressure and vascular connective tissue in castrated and noncastrated male rats.

Am J Physiol. 232, 617-621.

Fall 2008, Volume I Issue I

Carolina Scientific

Gamma Ray Bursts:

Chasing the Biggest Explosions in the Universe Rebecca Holmes, Staff Writer

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n the fourth floor of the Morehead Planetarium, UNC physics professor Dr. Dan Reichart and his team are studying the early universe. Along with graduate students and professionals, UNC undergraduates Summers Brennan, Rebecca Holmes, Mark Schubel, and Jana Styblova use remote-control telescopes in Chile to observe gamma-ray bursts, the most powerful explosions in the universe.

Gamma-rays are the most energetic form of electromagnetic radiation. They are far more energetic than visible light, the part of the electromagnetic spectrum the human eye can see. They are even more energetic than X-rays, which can pass right through human skin. Gamma-rays carry so much energy that they are only associated with violent phenomena like nuclear explosions.

Gamma-ray bursts (or GRBs) were first discovered in the 1960s by satellites specifically designed to detect high-energy radiation— but not from deep space. The satellites were intended to monitor Soviet adherence to the Nuclear Test Ban Treaty. The United States suspected the Soviet Union might hide illegal nuclear weapons tests on the far side of the moon.

The gamma-ray detectors on the satellites never saw evidence of such tests, but to the surprise of scientists, they did see bursts of

Fall 2008, Volume I Issue I

gamma-rays coming from deep predictions about what a supernova space. The bursts were short, associated with a gamma-ray burst lasting at most a few minutes [1]. should look like. Although there Two major explanations for has since been some conflicting the origin of these gamma-ray evidence, most astronomers now bursts emerged in the following believe that at least one type of decades. Both models involved gamma-ray bursts come from black the formation of a black hole with holes formed in the supernova an “accretion disk” of material deaths of massive stars. orbiting around it, but they differed When a black hole forms from on how that black hole was formed. the death of a massive star, it is One model suggested that the surrounded by a rapidly rotating black hole was formed during the accretion disk of material. As this supernova explosion of a massive material falls onto the black hole, it star. The other model suggested heats up, and the resulting energy that the black hole formed during causes some of the material still the collision and merger of two orbiting the black hole to shoot off neutron stars. Neutron stars are in narrow jets traveling at nearly extremely dense objects which are the speed of light. This ejected themselves the remnants of dead material moves through space, stars. More data were needed to colliding with other material. determine which of these models “Like a snowplow that collects too was actually happening [2]. much snow,” Dr. Reichart says, In 2002, Dr. Reichart discovered “it sweeps up gas and dust until something interesting in the data it decelerates quickly, violently for GRB 970228. There was an releasing most of its energy all at unexpected bright spot in the light Artist’s depiction of a GRB, as formed by the collapse of a large star into a black hole that the GRB’s afterglow emitted [3]. This “bump” in the afterglow was consistent with the added brightness from a supernova explosion [2]. Its brightness and the time at which it occurred matched theoretical

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Carolina Scientific

Close-up of a PROMPT telescope once in the form of a [gamma-ray burst]” [2].

Since gamma-ray bursts are so blindingly bright compared to other events in the universe, they can be detected on Earth even if they are extremely far away. GRBs are useful tools for studying the early universe because as astronomers look far off into the distance, they are also looking back in time. This is because light travels at a fixed and finite speed, so there is a time delay between when an event happens and when someone on Earth can observe it. For example, the sun in the sky on Earth is really an image of the sun as it was about eight minutes ago, because it takes about eight minutes for light to travel from the sun to the Earth.

Looking at something much father away than the sun, like a gammaray burst, is looking much farther back in time. In fact, in 2005, then-UNC undergraduate Josh Haislip discovered a gamma-ray burst which was then the farthest known object in the universe— nearly 13.5 billion light-years from Earth[4]. Its light had been traveling for 13.5 billion years before it reached a telescope.

Today, Dr. Reichart and his team

continue to observe and study GRBs using the PROMPT array of telescopes at Cerro Tololo near La Serena, Chile. PROMPT stands for Panchromatic Robotic Optical Monitoring and Polarimetry Telescopes. The array consists of six 0.41 meter Ritchey-Chretien telescopes which can be controlled remotely through the internet.

Each telescope is optimized to observe GRBs in a particular wavelength, or color, of light.

The telescopes can move rapidly across the sky, so when a GRB is detected by a satellite, PROMPT can automatically begin imaging the afterglow in multiple colors within seconds [5]. Students like Brennan, Holmes, Schubel, and Styblova then work to analyze the images from the telescopes and get information about the brightness of the GRB and how it faded over time.

Once this initial data from PROMPT has been reduced— sometimes within hours—student researchers submit a report to the gamma-ray burst scientific community. Then the research continues, especially if the GRB seems unusual or interesting.

Mathematical modeling with genetic algorithms can help refine scientists’ understanding of the mechanism behind GRBs. Data from images taken by PROMPT is fed into these models to improve them.

Astronomers think they have pinned down a source of energy— the supernova explosion of a massive star—which could power gamma-ray bursts. However, the mechanism by which this energy becomes gamma-rays is still unknown. A complete model

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of gamma-ray bursts will have to explain not only where these violent events get their energy, but also how the gamma-rays are produced. It will need to be able to predict the duration, brightness, color, and other characteristics of GRBs that Dr. Reichart and his students observe. Gamma-ray bursts which could be seen from Earth happen about once a day, each providing another opportunity to collect data and test predictions.

For now, the mystery remains and the research continues.

~Rebecca Holmes ‘11 is an

Astrophysics major and a Creative Writing minor.

References:

1. Schilling, Govert. Flash! The Hunt for the Biggest Explosions in the Universe.

1st ed. Cambridge, UK: Cambridge University Press, 2002.

2. Reichart, Daniel. (2003) “The Gamma-ray Burst/Supernova Connection.” Mercury September/ October 2003: 15-24.

3. P.A. Price, et al. (2003) “Discovery of GRB 020405 and its Late Red Bump.”

ApJ. http://arXiv:astro-ph/0208008v3.

4. J. Haislip, et al. (2006) “Discovery and identification of the very high redshift afterglow of GRB 050904.”

Nature 440: 181-183.

5. D. Reichart, et. al. (2005) “PROMPT: Panchromatic Robotic Optcal Monitoring and Polerimetry Telescopes.” Il Nuovo Cimento 28C: 767-770.

Fall 2008, Volume I Issue I

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Carolina Scientific

How Natural Products Aid in Drug Discovery and Synthesis

Drawing Board

Mary La, Staff Writer

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lants have been a source of natural medicines for as long as they have been viable food sources. For example, willow tree extracts have been known to reduce inflammation and pain.

More than seven millennia after its first recorded therapeutic use, one of its active compounds– salicylic acid–was chemically extracted, purified, and later fully synthesized. Though its painkilling effects were potent, salicylic acid was known to cause stomach ulcers. Near the end of the 19th century, Felix Hoffmann reduced its irritating effects by slightly modifying the compound to produce acetylsalicylic acid – more commonly known as aspirin [1]. This process exemplifies the importance of natural products in pharmaceuticals.

“Natural product” is a general category that includes true, naturally occurring bioactive agents, as well as fully synthesized compounds with natural pharmacophores (bioactive regions) [2]. By linking natural products to chemical and

Aspirin can trace its roots from the willow tree to the pharmacy counter.

Fall 2008, Volume I Issue I

biomedical laboratories, medicinal chemistry has vastly expanded the number of drug candidates and expedited the development of safe and potent medications.

Many drug discoveries from natural products originated from their therapeutic use in traditional or homeopathic medicine where some of the earliest examples came from the Chinese, Babylonians, Egyptians, and Greeks. Currently, due to advances in automation and chemical techniques, the screening of multiple natural products is the primary method of limiting the number of candidates to be tested for bioactivity and toxicity [3].

Novel drug lines may also stem from chemical modifications to the bioactive agent. In its original form, a natural product may be unstable, too toxic, too weak, or otherwise in a form that cannot be optimally used by the body. In this case, alterations must be made in order to produce an effective drug that can survive potential metabolism and extreme changes in biochemical environment before reaching its target.

Scientists can reverse-engineer the functional agents found in natural products by imitating what the organism can accomplish with highly specialized enzymes and signal pathways. As with any process, this has both benefits and difficulties. Most natural products are not easily renewable and can be expensive to cultivate. An

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efficient synthesis scheme for the target compound would make mass production of the bioactive agent manageable, but the structural complexity of most molecules of interest poses challenges in constructing multistep syntheses, stabilizing reaction intermediates, and recovering products efficiently.

Recent successes in identifying and synthesizing pharmacophores have made combinatorial syntheses more popular. In a combinatorial synthesis, modular components (in this case, building block pharmacophores) are identified, and large libraries of structurally similar but chemically distinct candidate compounds can be generated from the combinations of these constituents. Advances in analytical chemistry and focused screening have permitted better efficiency in synthesis and identification of new bioactive compounds.

Pharmacophores isolated from natural products have been modified and exchanged between parent drug structures in combinatorial schemes that generate “unnatural” compounds with new bioactivity.

Still, there are several drawbacks to the application of combinatorial chemistry to bioactive compound synthesis. The constituents must be easily interchangeable, so more complex pharmacophores may have to undergo other levels of modification before participating in

Carolina Scientific combinatorial synthesis. Peptides In one study, sixteen DesB are often used in combinatorial derivatives were produced via schemes due to their relatively total synthesis, then screened small size and commercial against two cancer cell lines availability. Also, only select sites (nasopharynx carcinoma), one on a candidate molecule contribute of which was resistant to the to its bioactivity. Optimal chemotherapy drug, vincristine. conformations and arrangement DesB and six select derivatives of pharmacophores might already were additionally screened against be determined by natural selection cell lines from human lung, breast, [4]. colon, and prostate cancers. The In reality, analyses of naturally activity of these derivatives was derived agents involve a mixture evaluated with ED50 (effective of compound library screening, in dose, 50%) values – the amount of vitro synthesis, and modification. the compound required to produce At the Natural Products Research an effect (in this case, inhibit cell Laboratories of the UNC School growth) in 50% of a test population. of Pharmacy, the Lee group has Ideally, minimal amounts of used a combination of these three the compound could be used to methods to produce derivatives produce significant results, so a of the flavonoid desmosdumotin lower ED50 is a mark of higher B (DesB) with bioactivity. Of higher anticancer the derivatives potency than the tested, it was parent compound. found that Flavonoids are modifications one of the classes at a particular of antioxidant position in the compounds DesB molecule that give plants (the 4’ carbon) Desmosdumotin B (DesB) their color and resulted in have recently attracted interest as the lowest ED50 values for the anticancer agents. Some tumor vincristine-resistant nasopharynx cells combat anticancer medication cancer line, but not for the by increasing expression of genes vincristine-susceptible line. In that aid in multidrug resistance addition, the derivatives with (MDR). Several of these genes, napthyl B-ring substituents had such as P-glycoprotein (Pgp) relatively low ED50 values for and MDR1, code for membrane all six cancer cell lines tested. proteins that actively transport As shown, analogs of a naturally bioactive compounds, including derived compound may lead to a anticancer agents, out of the new series of powerful anti-cancer cell. Therefore, much emphasis drug candidates [5]. has been placed upon finding The search for more effective compounds that regulate MDR bioactive compounds has become gene expression, and flavonoids are essential, especially in light particularly effective in tempering of drug resistance exhibited the activities of Pgp and MDR1. by tumor cells and bacteria.

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Naturally derived products, by offering drug candidates and potential pharmacophores to aid in total syntheses, have gained attention as the innovative source for structurally and functionally diverse compounds that could lead to the aspirins, morphines, and taxols of tomorrow’s pharmacopeia.

~Mary La ‘11 is a Chemistry and Spanish double major.

~With kind assistance and reviews from Dr. Michael Crimmins (Dept. of Chemistry), Dr. Kuo-Hsiung Lee (School of Pharmacy), and Dr. Susan Morris-Natschke (School of Pharmacy).

References

1. Mahdi JG, Mahdi AJ, Mahdi AJ, Bowen ID (2006) The historical analysis of aspirin discovery, its relation to the willow tree and antiproliferative and anticancer potential. Cell Prolif. 39, 147-155.

2. Newman DJ, Cragg GM, Snader KM (2003) Natural Products as Sources of New Drugs over the Period 1981 – 2002. J. Nat. Prod. 66, 1022-1037.

3. Muñoz O, Montes M, Wilkomirsky T. Plantas medicinales de uso en Chile: Química y farmacología. Santiago: Editorial Universitaria, S.A., 1999.

4. Ortholand JY, Ganesan A (2004) Natural products and combinatorial chemistry: back to the future. Current Opinion in Chemical Biology. 8, 271-280.

5. Nakagawa-Goto K, Bastow KF, Chen TH, Morris-Natschke SL, Lee KH (2008) Antitumor Agents 260. New Desmosdumotin B Analogues with Improved In Vitro Anticancer Activity. J. Med. Chem. 51, 3297-3303.

Fall 2008, Volume I Issue I

Carolina Scientific

Magnetoreception in Sea Turtle Navigation Rebecca Searles, Staff Writer

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t’s easy to see how an unprepared fisherman could find himself lost at sea—misguiding currents, no land-markers in sight, and every mile passed looks exactly the same as the mile before it.

Yet, below the surface, sea turtles are finding their way around just fine, even thousands of miles away from home. Researchers of the Lohmann Lab at UNC Chapel Hill are looking to find how these marine species and others engage complex sensory systems to navigate their open-sea migration routes.

Credit: www.unc.edu

Dr. Kenneth J. Lohmann, Professor of Biology at UNC

Most sea turtle species migrate intermittently throughout their lifespan, traveling back and forth between feeding grounds, mating and nesting areas, and

Fall 2008, Volume I Issue I

seasonal habitats. But even more baffling to scientists is the species’ demonstration of natal homing.

After 10-15 years of maturation, and thousands of kilometers traveled, they find their way back to the exact region they were born in to lay their eggs [1].

According to the research model, there are two components of information to marine animals’ ocean navigation: compass and map. Compass information is sometimes sufficient to orient an animal in the correct direction.

For example, sea turtle hatchlings migrate from the nest to the safety of deep water, and need only to know that they are moving in a constant offshore direction rather than toward a specific destination.

However, positional or ‘map’ information is needed to pin-point a specific goal or to guide the turtle along a complex migratory route.

Using ‘map’ information, marine species can identify their location relative to a goal and ensure greater accuracy in reaching the destination [1].

So how do sea turtles acquire this map and compass information?

Researchers have identified three significant types of directional and positional cues: geomagnetic, chemical, and hydrodynamic [1]. In recent years, however, researchers at Lohmann Lab have been focusing much of their attention on geomagnetic cues in

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order to better understand the role of magnetoreception in marine species’ navigation systems.

The concept of animals interpreting geomagnetic cues is based on the knowledge that they are able to sense the Earth’s magnetic field. This magnetic field is a constant environmental force that exists throughout all parts of the ocean, at all times of the day, and is unaffected by changes in weather and season. It is not surprising then, that animals have evolved a way to exploit this environmental feature as a guide that gives both directional and positional information.

Directional, or compass information, is the simplest of these. Among the animals that have been found to possess it are isopods, spiny lobsters, sea turtles, and salmon. Determining positional information from the Earth’s magnetic cues is a little more complicated.

There are several elements to the magnetic field that vary predictably across the surface of the Earth, which might enable animals to assess their geographic location.

The first is the way the lines of the magnetic field intersect the Earth’s surface to form inclination angles.

The field lines at the magnetic equator parallel the Earth’s surface, gradually becoming steeper as one nears either of the magnetic poles.

Therefore, inclination angles

Carolina Scientific however, is not. Another complication is that biological tissue is essentially transparent to magnetic fields. This means that magnetoreceptors are not necessarily located on an animal’s surface and could potentially be anywhere in the body in order for them to function. This turns a two-dimensional inspection task into a three-dimensional one, requiring some very advanced imaging techniques. Yet another difficulty arises with the likely possibility that there is no central structure for the magnetoreceptors.

Instead, they may be microscopic, intracellular structures scattered throughout the body, making detection nearly impossible [3].

Credit: Dr. Kenneth Lohmann

vary predictably with latitude, derive positional information and animals that are capable of from the Earth’s magnetic field are detecting these elements of the said to possess a ‘magnetic map.’ magnetic field would, in principle, It is important to note, however, be able to determine their position that the term ‘map’ implies relative to a certain area [1].

Three other elements of the Earth’s magnetic field may act as navigational cues: 1) the horizontal field intensity, 2) the vertical field intensity, and 3) the total field intensity. Like inclination angles, these three elements also vary predictably across the Earth’s surface, lending themselves to A juvenile green turtle swims in an navigation sense [2]. arena during a magnetic navigation Lohmann Lab’s research experiment has discovered that hatchling loggerhead sea turtles have the the human notion of specific inherent ability to detect both spatial representations, and it is magnetic inclination angle and unknown whether internal spatial field intensity. In one particular representations exist in animals, experiment, juvenile green turtles or how closely they resemble the were captured from a feeding human concept of a map [2]. ground and placed in an arena How ocean migrants manifest where they this physiological were exposed to ability remains a magnetic fields huge challenge to that existed 340 sensory biologists. km north or south Though scientists of the capture site. have discovered Turtles exposed the physical basis to the field from for nearly all other the northern area senses, and even swam south, a mechanism for whereas those magnetoreception that were exposed in bacteria, how to the field from animals perceive Figure 1: The four elements the southern area magnetic fields of a geomagnetic field vector, swam north. is still a great which could be another means These results mystery. One of for providing animals with imply that the the main reasons positional information. turtles utilized the question is a magnetic map that would have so difficult to answer is because led them back home had they been most nonhuman senses are displaced to the locations where extensions of human abilities, the two magnetic fields exist [1]. such as polarization detection and Animals with the ability to UV vision. Magnetoreception,

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~Rebecca Searles ‘11 is a Biology major. ~Special thanks to Dr. Lohmann for his help and resources.

References

1. Lohmann, K. J., Lohmann, C.M.F., Endres, C.S. (2008). The sensory ecology of ocean navigation. J. Exp. Biol.

211, 1719-1728.

2. Lohmann, K.J., Lohmann, C.M.F., Putnam, N.F. (2007) Magnetic maps in animals: nature’s GPS. J. Exp. Biol. 210, 3697-3705.

3. Lohmann, K. J., Johnsen, S. (2008).

Magnetoreception in animals. Physics Today. 31, 29-35.

Fall 2008, Volume I Issue I

Carolina Scientific

Fantastic Neutrinos and where to find them Lenny Evans, Staff Writer

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eutrinos are elementary Where Are They Found? neutrino capture, have proved particles as fundamental as The density of neutrinos in crucial to study the basic properties electrons or the quarks that make the universe is estimated to be of neutrinos [4]. up protons and neutrons. Unlike around 300 per cubic centimeter, electrons and quarks, neutrinos are so they are basically everywhere The Majorana Experiment nearly massless and chargeless. [5]. These neutrinos are believed UNC, along with 17 other This means that of the four to be relics of the Big Bang and institutions, is involved in an fundamental forces of physics, are the most abundant particles experiment known as Majorana neutrinos only interact via the weak in the universe. Many elementary that will try to determine whether nuclear force, which is not very particles, such as the proton and the neutrino is its own antiparticle powerful [1]. As a result, neutrinos electron, are charged, which made and possibly measure its mass rarely interact with matter, and in their discovery relatively easy. Not [3,4]. An antiparticle has the fact, over a trillion pass through until later did the neutron, which opposite charge as a regular you at any given second yet has no charge, get discovered. particle; when it interacts with only a couple will interact with Unlike the neutron, the neutrino its opposing regular particle, the the atoms in your body in your does not have a quality known masses of the two particles will lifetime [2]. This makes neutrinos as “color,” so it cannot interact be converted to energy according difficult to detect, leaving many with nuclei through the strong to Einstein’s famous relation E = things unknown about them. nuclear force [1]. The neutrino mc2. If the neutrino were its own The standard model of particle could interact gravitationally, but antiparticle, it would be called a physics is a theory formulated on the nuclear scale, this force is Majorana particle [7]. Though this in the 1970s that has required 1034 times weaker than the weak may sound like an unreasonable little change in four decades. It nuclear force [6]. Thus, almost all statement, other chargeless and predicted that neutrinos were neutrino interactions involve the colorless particles, such as the massless particles and that they weak force, which is responsible photon, are known to be their own differed from their antiparticles for beta decay. As a result, antiparticles. Neutrino theorists but there is now evidence that neutrinos can be produced in have relied on the idea that the refutes this. The value of these beta decay. Beta decay and many neutrino is its own antiparticle to masses is only weakly constrained of its variants, such as double formulate neutrino theories, but this - we only know that they are very beta decay, electron capture, and fact has not been experimentally light. It is also possible that Schematic diagram of beta decay, in which a neutron is confirmed [8]. the neutrino could be its converted into a proton, electron, and an anti-neutrino. Majorana, along with own antiparticle, but the other experiments like reactions in the experiments EXO and CUORE, are used to confirm or refute trying to determine this this claim have minimal property of the neutrino by half-lives on the order of ten searching for a hypothetical trillion times the universe’s rare process known as age [3,4]. neutrinoless double beta decay [9]. Double beta decay alone is a rare

Fall 2008, Volume I Issue I

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Carolina Scientific Proposed design of the Majorana detector, which has an array of Ge detectors surrounded by a copper shielding.

process in which a nucleus like 76 Ge undergoes two beta decays in rapid succession. The beta decays happen so quickly that due to the Heisenberg uncertainty principle, the first beta decay does not have to conserve energy, as long as the decay conserves energy as a whole.

Theoretically, if the neutrino were its own antiparticle, the two neutrinos that should be given off by each decay could annihilate one another according to one possible mechanism, and give all its energy to the two electrons given off in the reaction [2]. However, this decay has an extremely long halflife, on the order of ten trillion times the universe’s age [9]. The Majorana experiment will use germanium detectors enriched in the double beta-decaying isotope 76 Ge that will both be a source and detector of electrons from double beta decay. If the neutrinos take away no energy from the reaction, the electrons will take away all the energy of the reaction, and thus, if neutrinoless double beta decay can happen, we would expect to be able to detect two electrons with all the energy of the double beta decay.

However, because the process is so rare, any noise in the detector could drown out the signal being sought in the experiment. This noise is mostly due to decaying

radioactive nuclei that occur naturally on Earth or are created by cosmicrays [3,4,9]. One of the greatest goals of the UNC Majorana group is to find out how much this background noise will affect the experiment and find out how to minimize its interference.

UNC is the lead institution on the Majorana project; its team is led by project director, Dr. Wilkerson of the physics department. Dr. Henning, also of the physics department, was one of the leaders in the development of a computer program called MaGe that simulates the Majorana experiment. By using MaGe, researchers can alter various parameters, such as the amount of shielding placed around the detector, without having to spend money testing the various factors with actual experiments [10]. Others have been involved in testing the efficiency and spectrum output of germanium detectors that are similar to ones that will be used in the Majorana experiment.

Groups at UNC are also involved with studying the ultra-pure materials required for the detector construction and different prototype detectors. Through all the preliminary efforts, Majorana hopes to have a working detector with as little noise as possible, in order to detect, to a high degree of certainty, two electrons taking away all the energy of a reaction in neutrinoless double beta decay.

With these efforts, the Majorana team hope to achieve enough sensitivity to see this signal only once per year per tonne of

13

isotope[3,4]. Thus, it will take many years before some of the mysteries of the neutrino can be unveiled.

~ Lenny Evans ‘11 is a Physics and Math double major.

References:

1. Mohapatra, Rabindra, and Palash Pal. Massive Neutrinos in Physics and Astrophysics. River Edge, NJ: World Scientific Publishing Co., 2004 (3-5).

2. Esterline, James, and Mary Kidd.

Double Beta Decay. Durham, NC: TILT Presentation, July 9, 2008.

3. Wilkerson, John. The Majorana 0vbb Experiment. March 30, 2007. http://majorana.npl.washington.edu/docs/TheMajoranaExperiment.pdf 4. The Majorana Collaboration. Neutrinoless Double Beta Decay and Direct Searches for Neutrino Mass arXiv:hepph/0412300v1.

5. Bellerive, A. Review of Solar Neutrino Experiments. International Journal of Modern Physics.

6. Fundamental Interactions of Particle Physics Poster. cpepweb.org.

7. Griffiths, David. Introduction to Elementary Particles. Canada: John Wiley & Sons Inc., 1987 (20-24).

8. Ronquest, Michael. Explanation of Neutrinoless Double Beta Decay. Durham, NC: Lecture, June 19, 2008.

9. Henning, Reyco. The Majorana Neutrinoless Double-Beta Decay Experiment. Apr. 17 2005, http://majorana.pnl. gov/documents/HennningAPS05.pdf.

10. Chan, Yuen-dat, et al. MaGe – a GEANT-4 Based Monte Carlo Framework for Low-Background Experiments. arXiv: hep-nucl-ex/0802-0860v1.

Fall 2008, Volume I Issue I

Carolina Scientific

The Development of Synthetic Heparin Prashant Angara, Staff Writer

T

he anticoagulant heparin is one of the most widespread drugs today [1]. As a complex carbohydrate that thins blood, heparin has the ability to stop blood from clotting, making it incredibly useful in medicine. Often used to treat bleeding disorders, it is also used in heart surgery and the artificial kidney, among many other uses. This versatility creates an enormous demand for the drug, about 30-

Structure of Heparin Disaccharide Unit

40 tons per year, worldwide. The current method for meeting this demand is by isolating it from pigs, using somewhere between 400-700 million pigs [2].

However, the risk of impurities within the heparin samples is high, due to the anticoagulant’s lengthy isolation and purification process, and the lack of quality control and standardization of the pigs from which the heparin is derived. All of this led to the March 2008 heparin contamination, killing 81 people in the United States alone [1].

The raw heparin product was produced in China and imported to the United States [3]. However, this heparin was different in that it had been intentionally

Fall 2008, Volume I Issue I

contaminated with an inexpensive mimic of real heparin. The counterfeit heparin was able to pass routine testing, and was thus imported and used in the United States [3].

Heparin is a large carbohydrate that can be easily broken down into a disaccharide molecule that repeats 200-400 times. Scanning for impurities is often difficult because of the sheer size of the molecule.

Any of the disaccharide units can be replaced, as they were in the counterfeit, without significant changes in the chemical’s physical or chemical properties [2]. The fake heparin shipped into the United States had up to 20% of the active ingredient replaced by chondroitin sulfate [4]. This over-sulfated version of heparin was only found after detailed scanning [3].

How do we avoid such problems and contaminations in the future? The solution: synthetic heparin [2].

Synthetic heparin, as the name implies, is a manmade version of heparin that has its advantages over its animal-derived counterpart. Firstly, the production method for synthetic heparin is much simpler, and secondly, synthetic heparin could be more effective.

Synthetic heparin is composed of only heparin that contains the active ingredient, whereas the bioactive molecule constitutes a mere one-third of natural heparin. Therefore, a synthetic version would be more potent and, hopefully, have fewer side-effects on humans. One of the biggest side effects of heparin is heparin-induced thrombocytopenia. This occurs in about 4-7% of patients treated with heparin and causes platelet clots to form. These clots are similar to blood clots but are due to platelets rather than red blood cells [2].

Dr. Jian Liu of the University of North Carolina at Chapel Hill School of Pharmacy has come up with a method of creating this synthetic heparin. The technique uses bacteria, one chemical reaction, and two enzymatic steps to create a small amount of the desired synthetic variant. He harvests a disaccharide (figure 1) from the bacteria E. Coli and exposes it

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Carolina Scientific

Figure 1: The original disaccharide unit harvested from E. coli

to two enzymatic processes to create the desired disaccharide [2]. When many of these disaccharides are combined, the synthetic heparin is formed. Dr. Liu adds sulfate groups (SO3) to the NHCOCH3 and two of the -OH groups on the disaccharide. Sulfating the NHCOCH3 can be done via a chemical reaction because differentiating nitrogen from the -OH group is simple. However, differentiating the various -OH groups from each other is chemically difficult and must be done via enzymatic reactions. Because enzymes are very specific, it is possible to sulfate the correct -OH group [2]. Figures 2, 3 and 4 show the process used to create the synthetic heparin.

Figure 2: NHCOCH3 is changed to NH2SO3 via a chemical reaction involving NaOH and SO3-.

Figure 4: Another CH2OH is sulfated into a CH2OSO3 to create final synthetic heparin disaccharide.

This method of production only produces about 1 milligram of heparin, nowhere near the required amount [2]. Dr. Liu’s next goal is to try to create more synthetic heparin. He hopes to first synthesize between 1-10 grams, and then move to the kilogram level required for global production. He likes to think this is possible, but different equipment and synthesis optimization will be required. Research labs can only produce small quantities and are not designed for mass production. Currently, Dr. Liu is negotiating with various financial backers to obtain better equipment. He also hopes to make the market price of his heparin competitive with current heparin prices. The current price for animal derived, semipure heparin is about $4,000-$5,000 per kilogram and Dr. Liu hopes to get the price of his synthetic heparin close to this value. Even if his heparin is slightly more expensive, he rationalizes that the safety and purity of the product will allow it to compete with the heparin currently on the market [2]. With these goals in mind, he returns to the lab.

~Prashant Angara ‘12 is a Chemistry major. ~Special thanks to Dr. Liu for his time and help.

References:

1. Harris, Gardiner. April 22, 2008. “U.S. Identifies Tainted Heparin in 11 Countries”, New York Times.

2. Interview with Jian Liu, Ph.D 2008, 9/22/2008 3. Bogdanich, Walt. March 6, 2008. “Drug Tied to China Had Contaminant, F.D.A. Says”, New York Times.

4. Bogdanich, Walt. March 20, 2008. “Heparin Find May Point to Chinese Counterfeiting”, The New York Times.

Figure 3: The CH2OH is sulfated into a CH2OSO3-.

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Fall 2008, Volume I Issue I

Carolina Scientific

Autoimmunity:

How Defense Mechanisms Can Hurt Our Bodies David McInnes, Guest Writer

C

omedian Jerry Seinfeld quipped that a dermatologist’s entire profession “revolves around saying ‘Put some Aloe on it.’”

But dermatologists here at the University of North Carolina School of Medicine are knee-deep in research on a handful of insidious diseases of which most Americans have never heard: the autoimmune bullous diseases of the skin. The research laboratories here in the Department of Dermatology, where I have worked for the past three years, is one of the few research centers in the world focused on these diseases.

This emphasis on research, along with excellent patient care, has been a trait of the Department for many decades, and can be attributed to the late Dr. Clayton E. Wheeler and to Dr. Robert A. Briggaman. Dr. Wheeler had been a dermatologist at UNC since 1951 and became the first chairman of the Department in 1972. Even after stepping down in 1987, when Dr. Briggaman Artist’s depiction of IgG Above, B cells

Fall 2008, Volume I Issue I

became chairman (until 1999), Dr. Wheeler continued to see patients until shortly before his death, in 2007. Dr. Luis A. Diaz began his tenure as chairman in January, 2000. Dr. Diaz, Dr. Briggaman, and others speak admiringly of Dr. Wheeler as a great mentor and the driving force behind the current research efforts into the autoimmune bullous diseases.

Autoimmunity is the improper misuse of our defense systems in attacking ourselves. Essentially, immune cells mistakenly recognize elements of self as foreign invaders, and autoimmunity is medically defined as an immune response to self or autologous antigens. The diseases can be organ-specific, such as those of the skin or thyroid, or non-specific, as in the case of lupus [1].

Autoimmune bullous diseases consist of antibodies, primarily IgG class, which are produced by white blood cells known as B cells.

These antibodies act on the proteins that hold the epidermal cells to each other in the epidermis and to the dermis below. This causes acantholysis, or cell separation, and the formation of subepidermal bullae, or large blisters. The lion’s share of research performed by the UNC Department of Dermatology is on diseases that fall into two primary groups: the Pemphigus diseases, primarily pemphigus foliaceus (PF) and pemphigus vulgaris (PV), and the Pemphigoid

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diseases, mainly bullous pemphigoid (BP). Researchers at UNC-Dermatology, such as Dr. Diaz, Dr. David S. Rubenstein, and Dr. Zhi Liu, approach these diseases from several different angles [1].

Dr. Luis A. Diaz has been doing extensive research on PF for decades. PF autoantibodies target desmoglein 1 (Dsg1), a strongly adhesive cell surface protein which holds cells of the granular layer together, close to the surface of the skin. Ongoing work between Dr. Diaz and other immunologists is aimed at determining why B cells produce autoantibodies in the first place. While somewhat rare in the United States, PF is significantly more common in South America, particularly Brazil.

Among Amerindian populations on reservations in Brazil, there are several clusters of the disease in certain regions. There, the endemic PF found in these clusters is known as Fogo selvagem (FS), or “wild fire,” a Portuguese name given to the disease centuries ago by local inhabitants [2].

Dr. Diaz travels to Brazil every year to study and treat individuals at the Limao Verde Indian reservation, which has one of the highest prevalences of FS in the world, around 3%. While treating individuals there, he requests blood samples with which to perform FS research back at UNC. Dr. Diaz is convinced that there is a genetic

Carolina Scientific component to the disease, as well as a possible environmental factor, such as the hematophagous biting insects, which seem to trigger the disease. Dr. Diaz has compiled genealogies of the resident families and has been tracking the disease for decades in those families. His number one wish is to identify the cause of, and the cure for, PF/FS before he retires [2].

Dr. David S. Rubenstein is concentrating on PV, where patients produce autoantibodies against Dsg3, a binding protein found in the deeper superbasal cells. In order to prevent acantholysis, Dr. Rubenstein studies the downstream effects on the proteins that are bound and the effects of that binding on skin cells.

His work focuses on dealing with those effects and on preventing skin damage, even after binding occurs. Some positive results of his research are already being examined for practical applications of the pharmacological control of the disease [3].

Dr. Rubenstein has been working at UNC since he started his residency here in 1994. As attending physicians, he and Dr. Diaz regularly see patients at the Department’s two clinics, one here on campus in the Ambulatory Care Center and the other in the Southern Village community of Chapel Hill [3].

Dr. Zhi Liu’s research focuses on the pathogenesis of BP, and he is determined to learn as much as possible about new therapies to control the disease. BP targets the proteins that hold the epidermal basal cells to the dermis, along what is known as the Basement Membrane Zone (BMZ). The

BMZ of the skin consists of a wide variety of collagens and other matrix proteins.

BP produces autoantibodies against BP180, an epidermal basal binding protein, and causes deep and painful blistering. Research in Dr. Liu’s lab has progressed to the point that recently it has been shown that the epitope, or the precise antibody- Autoimmune bullous diseases cause severe blistering of the epidermis binding region, of the BP180 antigen is a very small stretch those with any of these diseases, of the protein known as NC16A. this perception couldn’t be more This protein and its gene have been untrue. sequenced, leading to the creation of “humanized” mice, which express human NC16A on their BMZ. Using these “humanized” mice, research on the effects of BP autoantibodies is proceeding very quickly, leading to important findings in the pathogenesis of this disease [4].

To a lesser degree, Dr. Liu researches other autoimmune diseases involving the BMZ proteins, such as Linear IgA Bullous Dermatosis, and ~David McInnes is a part time Epidermolysis Bullosa Acquisita. graduate student and a full time The clinical laboratory, where I research assistant in the UNC work with Dr. Diaz, is easily able dermatology department to diagnose these cases from blood samples and biopsies, obtained by clinicians from UNC and other References state dermatologists [4].

1. Culton, D. A. et al. “Advances in For those not in the field, it Pemphigus and Its Endemic Pemphigus can be difficult to understand the foliaceus (Fogo Selvagem) Phenotype: A Paradigm of Human Autoimmunity.” lengths to which research in a Journal of Autoimmunity. 30 (2008): particular field must go. While 1-14. millions of patients around 2. Diaz, Luis A., MD. Personal the world suffer from various Interviews. 8 Sept 2008. 10 Oct 2008. kinds of autoimmune diseases, 30 Oct 2008.

3. Rubenstein, David S., MD, PhD. Dermatology is often perceived Personal Interviews. 29 Oct 2008. 3 as a lesser field. Considering the Nov 2008. embarrassment, the discomfort, 4. Liu, Zhi, PhD. Personal Interviews. and even the risk of death, for 26 Sept 2008. 17 Oct 2008. 24 Oct 2008.

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Fall 2008, Volume I Issue I

Carolina Scientific

Reproductive Biology and Behavioral Neurecology: The Sockman Lab

E

ach summer, Keith Sockman and a crew of both undergraduate and graduate students travel to a wet meadow in the Colorado Rockies. They’re looking for one little brown bird: the Lincoln’s sparrow, Melospiza lincolnii, which migrates to highaltitude meadows for the summer breeding season. The Sockman crew spends two months in the field collecting data on the sparrows’ reproductive biology, which later provides ecological context to controlled experiments done in the lab.

In the Sockman Lab, undergraduates wishing to conduct original research in ecology have a wide range of opportunities.

Dr. Sockman eagerly encourages students to develop research projects in the field or in the lab on whatever topic most interests them. One student might use genetic techniques to determine nestling gender distributions.

Others might examine hormone distribution in the avian brain or study the relationship between song quality and mating success.

Fall 2008, Volume I Issue I

Elizabeth Bergen, Staff Writer Frequently, research topics are derived from direct observations of the birds in their natural environment each summer.

searching for nests, trapping and banding adult sparrows, or feeding hatchlings that have been collected from the field, among other tasks.

Crew members work eight hours a day and seven days a week.

The ability to cope with living in very small groups is crucial to semi-remote field research. For up to two and a half months the field crew lives in a single campsite with limited internet and cell phone access and only periodic trips into the nearby small town of Silverton, CO. Frequent bad weather, biting insects, and hard physical work compound social stress among members of the crew.

For those who can maintain good spirits in adverse conditions, Above: Lincoln’s sparrow; Top: the working on the Sockman field crew Molas Pass field site provides a precious opportunity.

Not only can undergraduates A Summer in the Field obtain serious research experience, Field research at 10,000 feet but Dr. Sockman puts forth extra is a grueling, but rewarding, effort to engage his crew members experience. Members of the field in the scientific process above crew typically wake up before and beyond the project at hand. sunrise to record birdsong and Evenings in camp are spent reading then spend the rest of the day scientific papers for journal club.

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Carolina Scientific Dr. Sockman enthusiastically challenges his crew to keep all their senses open and to stay alert for mysteries in the natural world that could inspire future research projects.

Undergraduates interested in joining Dr. Sockman’s summer crew are encouraged to review his recent publications on his website, www.unc.edu/~sockman.

Funding Sources and the Undergraduate Research Symposium A variety of funding sources may be applied to research conducted in the Sockman lab.

Students who work in the lab during the school year may apply for Undergraduate Research Support Grants of up to $750.

Eligible seniors who wish to do an honors senior thesis, which requires enrollment in Biol 395/396 and Biol 691H/692H, may apply for an Honors Thesis Research Grant of up to $1000.

First-year or sophomore students may apply for the Science and Math Achievement and Resourcefulness Track (SMART) program, which awards $2000 for a semester of research.

A Lincoln’s sparrow hatchling in the author’s hand

The Sockman lab pays members Symposium, which takes place in of its field research crew a living the spring. stipend of approximately $100 a How to Get Involved week. Students may also apply Interested in doing research in the for a Summer Undergraduate Sockman Lab? Send an email to Keith Research Fellowship (SURF) Sockman at kws@unc.edu and include: for up to $3000. The SMART 1) a resume or C.V. 2) a brief explanation about program also provides a $3000 why you are interested in summer fellowship. joining the lab Students who choose to take advantage of these funding For more information, visit: sources are invited to present www.unc.edu/~sockman a poster of their work at the annual Undergraduate Research

Avian brain sections in the Sockman Lab that will be optically imaged to determine hormone distributions

~Elizabeth Bergen ‘10 is a Biology major. Last summer she traveled to

Molas Pass with the SURF fellowship to study the relationship between arthropod food availability and nest timing. She currently is completing her project in the Sockman lab.

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Fall 2008, Volume I Issue I

Carolina Scientific

Yes to NO:

UNC Researcher EXPLORES Molecule for Biomedical Advances Natalia Davila, Staff Writer

Credit: http://www.chem.unc.edu/people/faculty/schoenfisch/group/index.html

H

ow does an undergrad at the University of Kansas go from a major in German and a mild interest in Chemistry classes to becoming a professor and researcher of biomaterials, sensors and new therapeutics at the University of North Carolina at Chapel Hill?

Internationally recognized research scientist Dr. Mark Schoenfisch was, like many undergraduates, undecided about his career path and even his major until a friend suggested talking to a professor about joining a research lab. His curiosity broadened working in the lab because, as Dr. Schoenfisch puts it, he could see the applications of chemistry and the connections between different branches of science more easily than simply doing chemistry homework.

Credit: Mark Schoenfisch

Dr. Mark Schoenfisch, Assistant Professor of Chemistry

Fall 2008, Volume I Issue I

The enthused graduate went on recognized as a toxic air pollutant, to earn his Ph.D. in Chemistry at the versatile gas acts as a natural the University of anticoagulant, a Arizona where neurotransmitter he worked with and an pacemaker antibacterial electrodes agent in the and explored immune system their surface [2]. Nitric oxide chemistry. At kills bacteria Arizona and and thus may during his be useful for postdoctoral designing more years at the biocompatible University of sensors and Michigan, the implants.

A connection significant b e t w e e n limitation chemistry and in the use of Lewis Diagram and 3-D Model of biomedical subcutaneous Nitric Oxide engineering in vivo developed in his sensors (used research, which he later brought to for monitoring physiological UNC. status of patients) and implants, In 2000, the Schoenfisch lab such as catheters and artificial officially began with projects prosthetics, is their inadequate spanning analytical chemistry, biocompatibility [3]. Days, even organic chemistry, polymer hours, after implantation, the chemistry, microbiology and human body responds to these biomedical engineering. Over devices as foreign objects, which the years, the group’s interest triggers platelet and protein has expanded to include on adhesion, biofilm formation and investigating protein adsorption encapsulation of the device [1]. and designing nitric oxide (NO) These biological responses not releasing materials [1]. The latter only compromise the performance covers a wide array of projects of the sensors and implants, but and new techniques being used by also cause infection and pose other the Schoenfisch group. health risks [4].

Testing NO’s roles in human Dr. Schoenfisch’s group, physiology is a relatively new consisting of postdoctoral fellows area in chemistry. Typically and graduate and undergraduate

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Carolina Scientific Credit: Mark Schoenfisch

B)

A)

Figure 1. A) Subcutaneous electrochemical glucose sensor plagued by bacteria biofilms and poor wound healing (e.g., fibrous encapsulation). B) Nitric oxide-releasing sensor that eliminates biofilm and reduces capsule thickness thereby enhancing the analytical response properties of the device.

students, is tackling the challenge of improving the biocompatibility of these sensors by developing polymer membranes that make use of active release strategies. Among the many focuses of the lab, they are investigating NO release coatings via diazeniumdiolate NO donors that function as natural NO releasing agents. Nitric oxide has proven to inhibit platelet adhesion, suppress bacterial growth, promote wound healing and kill parasites when exposed in the human body [2]. Schoenfisch group studies have also revealed that the slow release of NO from a polymer membrane, for instance on in vivo sensor surfaces, reduces biofilm formation and bacterial adhesion [4].

Though the beneficial characteristics of NO seem favorable, a few problems persist when using this gas: the uncontainable and disorderly characteristics in the body and the possibly toxic effects [5].

NO oxidizes quickly and is very reactive. Therefore, NO storage has been one of the biggest challenges. The Schoenfisch team constantly works to develop new materials that store more and more quantities of the molecule and effectively control the release of NO [5]. The latter is a particular challenge as well because exposure to NO in high quantities can be toxic [2].

Although they usually fit under the umbrella of analytical chemistry, Dr. Schoenfisch runs projects and a laboratory that involve a variety of scientific disciplines including analytical, polymer and organic chemistry, physics, and biomedical engineering. A man who simply calls himself a chemist, Dr. Schoenfisch professes that collaboration is a key component of his research and multidisciplinary laboratories are important for solving medicine’s most significant problems [1].

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~Natalia Davila ‘11 is a Studio Art and Chemistry double major. ~Special acknowledgement to Dr. Schoenfisch for devoting his time and resources.

References:

1. Interview with Mark H. Schoenfisch, Ph.D. 2. L.K. Keefer, CHEMTECH, 1998, 28(8), 30-35.

3. J.H. Shin and M.H. Schoenfisch, The Analyst, RSC, 2006, 131, 609-615.

4. E.M. Hetrick and M.H. Schoenfisch, Chemical Society Reviews, 2006, 35, 780-789.

5. D. Jacobs, Endeavors, Carolina Alumni Review, 2007, 24, 7-9.

Fall 2008, Volume I Issue I

Carolina Scientific

Physics Tips for Living a Healthy and Happy Life at UNC

Kelly Bleaking, Staff Writer

A

sk someone what they think about physics and you will hear “physics is difficult and boring!” But there are so many cool components to physics about which most people don’t know. For instance: do you know how to have extra time to study for your tests? How to travel through time? How to avoid being eaten by black holes? The following are some tips for navigating the nuances of physics for successful adventures here at UNC.

: How to Find Extra Time...

#1 TIP

A

in Davis Library!

ccording to Einstein’s Theory of Relativity, time is different at different heights: a clock farther from the surface of the earth will tick faster. So you should study on the eighth floor of Davis Library because you will have more time to study compared to those unknowing students on the first floor. (Caution: the time it takes you both to wait for, and ride up in, the terrifying elevators - built before most of us were born - will negate the time you save; but who’s counting?).

: IP #2

T

Time Traveling to Beat the Curve!

Y

Davis Library

ou’re in class one day and you’re waiting anxiously for your test results from a ridiculously hard test. The class average was a 43, so you think that, this time, the professor will have to curve. (After all, there’s no way anyone got above a 70, right?)

You glance over at the guy sitting next to you, and for the third time in a row, he’s received a perfect score! Looks like there’s no curve for you, again.

But it’s okay: he’s from the future and simply not telling. Relax. All you have to do is be his friend, and next time, he will take you back in time with him. Currently it is believed that time travel forward in time is possible and time travel backwards is not; moving very fast, traveling forward in time is possible, as you would have a different relative time compared to Earth time (after several years of traveling very fast in space, a twin who went into space would be younger than his twin who stayed on earth). While traveling back in space is not currently considered

Fall 2008, Volume I Issue I

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Carolina Scientific possible; however, the theory is that wormholes, or shortcuts, between two points in space, exist. If people could travel through this wormhole, they could travel backwards in time. But the gravity of a wormhole would cause it to collapse almost immediately after forming. It could be possible in the future to produce some kind of antigravity device that could keep the wormhole open long enough to travel through it (check with the guy with the perfect scores!).

:

#3 TIP

Y

Gosh-darned Black Holes!

our new friend agrees to take you on a time travel expedition. He’s just glad you don’t hate him (like everyone else does). So you go in his spaceship and he says “all you have to do to improve that test grade is ride this blue probe through the black hole in the distance.” You’re still not so sure about this guy (after all, if he’s from the future, and has an awesome spaceship, why does he waste time in class instead of on saving the world?) And he does have a suspicious look in his eye and he really wants you to go into the black hole. You vaguely remember something about black holes, but what was it? Thankfully, as a physics student, you would remember that if you were on a spaceship 15,000 km from a black hole five times the mass of the sun, and you sent a probe that emits a blue glow towards the black hole, from your point of view, the probe would take an infinite amount of time to reach the surface of the black hole. However, you wouldn’t be able to see it with the human eye. As the probe falls, the gravity of the black hole causes the light of the probe to have longer and longer wavelengths. This means that the light from the probe will turn from blue to green to yellow to red and will eventually have a wavelength that you cannot see.

If you had infrared goggles, near the surface of the black hole, the gravity would be so much stronger on the part of the probe closest to the black hole than on the part farther away, that it would stretch the probes out like spaghetti, An artist’s depiction of a black hole, Credit: NASA rip it into atoms, and then even rip the atoms apart. To the probe, or someone with the probe, there would be no change of time or color. He would simply get close to the black hole and be ripped apart. So if your buddy is trying to convince you that you should be the one to enter the black hole to figure out what’s inside, and he tells you he’ll watch and see what happens, don’t do it! The upside is that now you know better and aren’t going to be ripped into atoms, but the downside is you’re trapped in a spaceship with someone who just tried to kill you (no wonder everybody hates him).

Perhaps instead of time travel and black hole expeditioneering you should take your chances on the 8th floor of Davis. Good luck!

So if you think you’ve seen the light and discovered how phun physics can be, you should join UNC’s Society of Physics Students! To find out more information, contact Jon Toledo at toledo@physics.unc.edu or join the listserv: uncsps@listserv. unc.edu.

~Kelly Bleaking ‘11 is currently undecided in her major.

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Fall 2008, Volume I Issue I

Carolina Scientific

SURF: Cambodian Drinking Water Alia Khan, Staff Writer

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s I stared out the window of the plane while flying into Cambodia, I could see two of the major rivers of this region- the Mekong and the Tonle Sap. The further we descended, the clearer I could see the land below me, and the more I realized how very different the landscape, climate, and culture would be from the Old North State I had recently left. As the plane touched down I Cambodia, a country in knew I was in for an Southeast Asia amazing adventure over the next two months and was filled with motivation to dive headfirst into my field research while assimilating into the Cambodian way of life.   Through a Summer Undergraduate Research Fellowship (SURF), I had the opportunity to travel to Kean Svay, Cambodia to conduct environmental microbiology field research in the summer of 2007.

Effective water treatment has been the most important factor influencing advances in public health in the last century [1]. However, 1.1 billion people still lack access to improved drinking water and as a result suffer from water-borne diseases such as dysentery and diarrhea. In developing countries such as Cambodia, surface water is polluted with pathogens and ground water is contaminated with heavy metals such as arsenic. Water disinfection supplies are often inaccessible for typical Cambodian families living on less than $2 US a day, and the amount of disinfectant needed in areas with highly polluted water can often be too toxic or unpalatable to consume on a regular basis. In order to identify which waters are contaminated, there must be procedures to assess

Fall 2008, Volume I Issue I

water quality, as well as to evaluate the effectiveness of the microbial and chemical methods used to treat water [1]. The aim of my studies was to compare the efficacy of four alternative low cost/simple methods to detect E.coli with the standard US-EPA method, membrane filtration. If the results proved similar, the need for expensive methods could be deemed unnecessary, therefore making identification methods more accessible to developing communities.

Credit: Alia Khan

Open well in Kean Svay, one of the three types of water sources tested.

  The base for my research was my generous host, Resource Development International- Cambodia (RDI-C). RDI-C is a local non-governmental organization (NGO) based in a village in Kean Svay, about 30 minutes outside of Phnom Penh by car.

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Carolina Scientific membrane filter method, and hence provide cheaper and more accessible methods to identify contaminated drinking water for developing countries such as Cambodia.

The on-the-ground perspective that I gained to water and sanitation issues facing rural Cambodia was an invaluable experience, and I learned a Credit: Alia Khan tremendous amount The RDI-C Microbiology Lab *Note the shoes by the door from my advisor, This NGO has on-going tangible community-based Dr. Mark Sobsey, my host organization RDI-C, projects, ranging from clean water and sanitation to sustainable agriculture and head-lice soap production. and its director, Dr. Mickey Sampson. Having the During my stay I had the opportunity to accompany opportunity to work side by side with Cambodian a work-crew to complete a rainwater catchment staff, as well as conduct my own research miles tank in Preak Russai- a remote Cambodian village away from my sponsoring advisor, gave me the with drinking water 200 times the World Health opportunity to grow as an independent academic Organization safe-level of arsenic. Field work was researcher while also enriching my appreciation for one of the most rewarding aspects of my trip, as well the variety of atmospheres in which similar research as the relationships that I formed with the NGO staff can be conducted. and local villagers. Throughout my study, I had the benefit of collecting my own water samples from common drinking water sources from village homes throughout Preak Thom (the village RDI was based in), as well as surrounding areas- usually travelling by ‘moto’ (motorcycle).

While there are obviously many cultural differences between the U.S. and Cambodia, as a science student, one aspect that greatly intrigued me is how these differences translated into the lab atmosphere. In most western laboratories, it is required by law to wear closed toed shoes. This was never a problem in Kean Svay, as it would have been culturally improper not to remove my shoes before entering the lab.

By the end of two months of research, I found evidential support for the effectiveness of the alternative methods tested. These methods could be used to replace the more expensive standard E.coli

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~Alia Khan ‘09 is an Environmental Science and Engineering major.

References

1. Madigan, Michael T, Martinko, John M., Parker, Jack.

Brock Biology of Microorganisms. 10th ed. Upper Saddle River, NJ 07458, Pearson Education, Inc, 2003.

Fall 2008, Volume I Issue I

Carolina Scientific

Undergraduate Summer Research Spotlights Compiled by Ann Liu, Staff Writer 1. How did you hear about your program?

Last fall, I was invited to an event on Facebook. The event was an information session about Summer Undergraduate Research Fellowships. After the information session, I went to the Office of Undergraduate Research to find out all I could about their fellowships. I applied for a SURF and also found out about the Science and Mathematics Achievement and Resourcefulness Track Program (SMART). I decided to apply for this program as well, and this is the one I chose to participate in last summer.

2. Describe the application process. Any tips/suggestions?

The application process is pretty simple for the SMART program. You must fill out an application online describing your general information, the various science and mathematics courses you have taken in college and high school, and why you would be competitive for the program. The last part is an essay. I suggest spending a good amount of time on the essay and definitely having a professor proof read it for you. After your application has been reviewed

by Dr. Parikh and Dean Woodard, you may be asked to come in for an interview. This is the most important part of the application process. If Dr. Parikh and Dean Woodard feel that you would be a nice addition to the program, then you’re in! I would suggest dressing in business attire for the interview. It’s always better to be overdressed than underdressed, and in business attire, you will seem more impressive. Be yourself in the interview.

Don’t get nervous. If the program is meant for you, then you have nothing to worry about.

3. How did you find a lab to work for and what was your research about?

I found a lab before I came to UNC, and began working in that lab just before my first semester of college. I was able to do this through my professor of medicinal chemistry in high school. I would recommend others to search their majors’ websites for professors willing to accept undergraduate students into their lab. Although, if you are interested in the SMART program, they will match you with a professor if you don’t already have a lab to work in. My research was about the RyR1 ion channel, which controls muscle contraction. I worked on trying to find a model through computer simulations to imitate how it works.

4. Overall, how was your research experience? What were some positive aspects? Negative aspects?

Random fun facts?

My research experience was amazing. It’s the best way to spend a summer. I was paid for something I love to do anyways.

I got to know people in my lab so well. Everyone becomes sort of a family in a lab. The people in my lab now even help me with some of my classes if I have questions. I learned so much this summer, including computer programming, how to use Matlab and Mathematica, all about ion channels, and so much more. It was an amazing learning experience. I would say that it was a little annoying to have to compile PowerPoint presentations of my weekly progress, but in the end, it was completely worth it. I am so much more comfortable speaking about my work in front of an audience now, and at the end, we, the SMART fellows, were able to present our work to many others including our families. Also, the SMART program introduced me to the Alliances for Graduate Education and the Professoriate (AGEP) program. I am now an AGEP fellow, which is also an amazing experience. To find out more about the AGEP program, go to http://www.unc.edu/agep/. To find out more about the SMART program, go to http://www.unc.edu/depts/our/students/fellowship_supp/smart.html.

To find out more about the SURF program, go to http://www.unc.edu/depts/our/students/fellowship_supp/surf.html.

~Brittany Fotsch ‘11 is a Chemistry major and currently works in the Dokholyan Lab at UNC.

Fall 2008, Volume I Issue I

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Carolina Scientific 1. How did you hear about your fellowship/program?

Found out about the Baylor SMART program at Rice University from Google

2. Describe the application process. Any tips/suggestions?

The application consists of a general information sheet, transcript, listing career goals, 2 letters of recommendation, a page about prior research and training experience, a skills assessment/evaluation sheet about what you know/can do. (Prior research experience is not absolutely necessary.) About 95% of the participants were rising juniors/ seniors. They give preference to students who have in interest in graduate school/medical school.

3. How did you find a lab to work for and what was your research about?

I was matched with a lab based on my interests. (You list 3 areas of interest in your application.) If you have a specific request to work in a particular lab, you can also list it on your application. My research was nutrition-related and about iron bioavailability from Arabidopsis thaliana leaves.

4. Overall, how was your research experience? What were some positive aspects? Negative aspects? Random fun facts?

It was great! Positive aspects include a seminar series (everyday from 12-1) when we had a speaker come and talk about their research, evening activities, career development sessions, as well as social activities. The people I met there came from very diverse backgrounds—students from all over the nation, several from Puerto Rico, as well as international students. There were also many opportunities to get career advice and opportunities for job shadowing (very helpful!!) Rice University dorms are awesome! Negative aspects include repetitiveness in lab experiments but this may be true of many types of research. Houston is also very hot in the summer but there is a lot to see there.

~Lalitha Kunduru ‘11 is a Biochemistry major and worked in the Etcheverry Lab at the Baylor College of Medicine this summer.

NEED $$$ FOR A SUMMER IDEA? Summer Fellowship Deadlines

1. Summer Undergraduate Research Fellowship (SURF) DEADLINE: February 26, 2009 SURFs are major awards (at least $3000) to enable undergraduates to engage in research, scholarship or creative performance under the guidance of faculty advisors (and possibly also graduate student mentors) for at least 9 weeks (20 hours/week) during the summer.

2. Science and Math Achievement and Resourcefulness DEADLINE: March 16, 2009 Track Program (SMART) The SMART program provides an excellent, paid (~$3000) opportunity for rising sophomores to spend eight weeks during the summer doing 20 hours of research per week with a faculty mentor. SMART is sponsored by the National Science Foundation and is a part of its nationwide Alliance for Minority Participation initiative to increase the number of underrepresented minority students who earn degrees in science, technology, engineering, and mathematics (STEM) disciplines.

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Fall 2008, Volume I Issue I

“If we knew what it was we were doing, it would not be called research, would it?” ~Albert Einstein

Carolina Scientific Fall 2008 Front Cover: A 4-day old Lincoln’s sparrow, credit: Elizabeth Bergen This publication was funded at least in part by Student Fees which were appropriated and dispersed by the Student Government at UNC-Chapel Hill.