Fall 2009 Issue by Carolina Scientific

Volume II, Issue I

Fall 2009

carolina

sc1ent1fic Undergraduate Magazine

UNC-Chapel Hill

Carolina Scientific

From the Editors To our readers: â&#x20AC;&#x192; In our second year of publication, we have worked to expand our articles beyond just biology and chemistry. We are especially excited to have writers in physics, public health, and even a bit of network science! As in previous issues, we are highlighting the research our peers are conducting on our campus. In this issue, we have focused on students who completed a summer research project funded by Summer Undergraduate Research Fellowships. We hope you enjoy this magazine as much as we have enjoyed putting it together! ~Adele, Ann, Lenny, and Natalia

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

~Natalia Davila is ~Lenny Evans is a ~Adele Ricciardi is ~Ann Liu is a junior majoring in a junior majoring junior majoring in a junior majoring in Biochemistry and in Studio Art with a Physics and Math Biochemistry and Biology minor in Chemistry Business

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.

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Carolina Scientific

Contents 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 43

The RESOLVE Survey: A Closer Look at the Physics of Galaxies

Rohan Shah

Molecular Discrimination of Lung Cancers

Keith Funkhouser

Network Science: The Science of Connections Kevin Macon and Amanda Traud Cell Signaling Therapy - Hope for a Seemingly Hopeless Cancer Abby Bouchon Helping to Break the Habit: Naltrexone and Alcohol Dependency

Mary La

BPA: Promoting Aggressive Behavior in Young Girls

Rebecca Searles

A Nervous Development: from Neural Tube to Nervous System

Amy Abramowitz

Keeping the Beat Ranjan Banerjee A Scientific Callin’: Probing Deeper into Colon Cancer Frank Mu Reproductive Immunity: Toll-like Receptors in the Human Endometrium

Vahini Chundi

Arsenic in Drinking Water? A Dietary Approach to Improving Arsenic-Induced Diabetes Jesse Lomas The Histone Code Hypothesis

Prashant Angara

Tag, You’re It! Discovering a New Receptor to Analyze Gene Repression

Garrick Talmage

Not So Simple Symplekin: Analyzing the Role of Symplekin in Histone Pre-mRNA Processing

Michelle Lin

A Superbubble Bath

Apurva Oza

Genetic Divergence and Reinforcement of Species Differences

Elizabeth Bergen

It’s Gonna be a Long Night...

Ameer Ghodke

Yeast, A Human Stand-In

Mary Gallo

Undergraduate Research Spotlight: SURF

Compiled by Ann Liu

Acknowledgements

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Carolina Scientific

The RESOLVE Survey: A Closer Look at the Physics of Galaxies Rohan Shah, Staff Writer

ave you ever looked outside and wondered what the universe really looks like? The billions upon billions of tiny dots you see in the sky are just parts of a bigger whole: a galaxy. Headed by Professor Sheila Kannappan, the RESOLVE (REsolved Spectroscopy Of a Local VolumE) Survey here in Chapel Hill is trying, using data analysis revolving around physical characteristics of celestial bodies, such as stars and nebulae, to systematically map out this unknown. An undergraduate, Xuan Liu, has been working with Professor Kannappan and the RESOLVE Survey team for the past two and a half years. He has been involved with data collection and analysis [1]. The team used the remote controlled observatory, Soar, in Chile to take telescopic data and high-resolution pictures Flexible Image Transport System (FITS) images. FITS are photograph files designed specifically for scientific purposes such as photometric and spatial analysis of the pixels. Using a unique astronomical camera in the telescope, the team was able to take these ultra-high resolution photographs and use them to map out different parameters for each celestial body [1]. These parameters include redshifts and blueshifts, which are the blurs associated with celestial movement (imagine taking a picture of someone running). The team used a color gradient to disperse the blur light from the pictures to create emission and absorption spectra [1]. The in-

Figure 2. Emissions spectrum of redshifts and blueshifts depending on celestial body movement.

creased exposure forms the redshift when a star is receding from a detector and a blueshift when a star is approaching the detector (see Figure 2). These shifts help determine measurements of velocity and celestial luminosity. Luminosity is the rate at which a source radiates light in all directions, which it makes it key in determining a body’s translational motion, or movement through space. These parameters also include wavelengths and frequencies of light emissions, which help determine the physical and chemical properties of the body, or what elements it is made of. The pertinent information, such as color-shifts and spectra, cannot be extracted without the use of some advanced mathematical algorithms. The team employed the use of Interactive Data Language (IDL) primarily used for image analysis and array processing. Every pixel on a FITS file can be understood as a varying number [1]. A higher number symbolizes a more intense light. IDL allows these picture files to become databases of astronomical data. Mathematical algorithms used by IDL then create three-dimensional graphs with information regarding magnitude of intensity of light (see Figure 1). Different light intensities aid in both determining the composition of the body as well as its movement data. This is imperative in the team’s usage of the FITS images, as the bulk of the team’s data is extracted from these files. The analysis of the different luminosities and color shifts give the team the ability to determine the

Figure 1. 3-D model created using IDL.

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Carolina Scientific

Figure 3. Radical velocity maps of a galaxy.

celestial body’s radial velocity in space. This radial velocity shows how that object moves in space in relation to what can be seen from earth. The team hopes to create maps which are basically a grid of radial velocities [1]. The information extracted from these maps will allow the team to map out the inclination and orientation of galaxies in space. Inclination is the tilt of a celestial body’s movement. Based on the observation data taken from the telescope and velocity maps, they will also be able to create a library of model galaxy velocity fields which allow an increasingly multilateral representation of how actual galaxies move [1].

Enhancing and expanding this library of maps will ultimately create a concrete modeling structure from which stronger patterns of movement and orientation can be drawn out. These patterns will then lead to a better understanding of how exactly our universe functions as a spatial entity. Given the inclination of galaxies and their radial velocity determined through the use of the FITS files and IDL, the RESOLVE survey can then find the rotation velocity of galaxies. The difference between radial and rotational velocities lies in line-of-sight apparent rotating velocity versus absolute rotating velocity in space. The radial velocity is not the actual speed at which the galaxy is rotating. Using the rotational velocity, important information such as total galaxy mass can be extracted, which implies numerous other currently-unknown physical properties such as universal orientation, gravitational effects, and even further into dark matter mass limits [1]. Ultimately, what the RESOLVE Survey shows is that we can understand how our universe is filled and physics associated with it, just like organelles within a cell. As we can determine a cell’s nature by its internal organelles, the celestial bodies that encompass a galaxy play a huge role in determining its nature. Magazines have published their speculations and guesses regarding absolute celestial movement, but this UNC-based team, with undergraduate students such as Xuan Liu and his fellow researchers hard at work, is pioneering the way into finally figuring out, using concrete math and physics, how exactly the world outside our world moves.

Rohan Shah ‘11 is a Biology major with a double minor in Chemistry and Japanese

References

1. Interview with Xuan Liu, 09/30/2009.

Figure 4. Milky Way galaxy.

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Carolina Scientific

Molecular Discrimination of Lung Cancers Keith Funkhouser, Staff Writer

or Greg Tsongalis, a Pathologist at Dartmouth-Hitchcock Medical Center, it was a routine case: a female smoker with a history of head and neck carcinoma is screened and found to have a lung tumor. The microscopic appear-

William B. Coleman, Ph.D., Professor and Director of Graduate Studies in the Department of Pathology and Laboratory Medicine

ance of the tissue samples from each site appeared identical, such that simple observation could not determine the clonal relationship of the cancers (Figure 1). In one case, the cigarette smoke carcinogens could have caused two independent primaries, i.e. a head/ neck primary and a lung primary. The alternative possibility would be that the head/neck carcinoma “metastasized,” or spread through the bloodstream, to the lung. In the first case, the two carcinomas would be staged separately, surgically removed, and the patient should have a high chance of sur-

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vival. In the second case, the patient would be judged to have high stage head/neck carcinoma, treated with chemotherapy instead of surgery, and have a significantly lower chance of survival [1]. To further investigate, Dr. Tsongalis called upon colleague William B. Coleman, Ph.D., Professor and Director of Graduate Studies in the Department of Pathology and Laboratory Medicine at UNC. Coleman understood the nature of the clinical dilemma, and hypothesized that there may be a genetic similarity between a primary and a metastasis which is not present in two independent primaries. Due to the genetic instability of cancers, he knew that a primary tumor could lose alleles (one of the two copies of the DNA) in a metastasis, but not gain them. He set out to apply this

concept to develop a molecular test that could determine the lineage of such tumors [1]. Due to the fact that a metastasis can show allelic loss but not allelic gain, certain conclusions can be reached based on genetic analysis. Namely, if alleles are lost in only one direction from Tumor A to Tumor B, it suggests that Tumor B is a metastasis of Tumor A. If alleles are lost in both directions, known as discordance, Tumors A and B must have arisen independently (Figure 2) [2]. Based upon this logic, Dr. Coleman and his colleagues compared allelic variance between pairs of tumors using short tandem repeat (STR) microsatellite markers. STRs occur in DNA when a pattern of 1-5 nucleotides is repeated in sequence. The polymerase chain reaction (PCR) process is

Figure 1. Patients’ cancers of the head/neck and lung are indistinguishable histopathologically; a molecular basis for discrimination is necessary [2].

Carolina Scientific Figure 2. The left image suggests that tumors A and B are independent primaries, due to the discordant changes in alleles (i.e. for one microsatellite marker, A loses alleles to B, but for the other marker, B loses alleles to A). In the right image, the unidirectional loss of alleles from A to B suggests that A metastasized to B. Figure 3: A portion of the “genetic profile” of a patient, viewed on a polyacrylamide gel. Two tumors T1 and T2 were analyzed for the three different microsatellite markers shown. In the first and second images, T1 loses an allele to T2; however, in the third image, T2 loses an allele to T1. Such discordant changes suggest that T1 and T2 are independent primaries [2].

used to amplify these polymorphic STR sequences. Since the lengths of STR alleles are highly variable in the human population, allele lengths for a set of STRs is unique to a given individual, and can be used for parentage or forensic testing. STR alleles, which are lost in the tumor (loss of heterozygosity, LOH), allow creation of a unique “genetic profile” for each tumor. Their goal was to use the differences identified to look for plausible lineage relationships that would suggest metastatic disease, versus discordance that would suggest independent primaries (Figure 3) [1]. When tumorigenesis occurs, there are certain genetic aberrations that are inherent in the neoplastic clone, whether they are DNA breaks, rearrangements, insertions, deletions, or point mutations. Because these can result in LOH, if Tumor A metastasizes to Tumor B, there will be a traceable genetic relationship. Tumor B will be genetically identical to Tumor A, except that certain variations will have occurred due

to the cancer genome’s instability. The more alleles that are shown to be expressed in Tumor A but not in Tumor B, the more confidently one can say that Tumor B is a metastasis of Tumor A [2]. In contrast, if any alleles are present in B that are not present in A (discordant genetic variation), then tumor B cannot be a metastasis of Tumor A. If different allelic gains are seen in comparison of the genetic profiles of A and B, then they must represent two independent clonal neoplasms. The clinical implications of this study are significant. Distinguishing multiple independent primary cancers from metastatic cancers has a marked impact on tumor staging, the most important determinant of prognosis (survival). In addition, the study has potential to be applied to other forms of recurrent cancer, such as breast and colorectal cancers [1]. In the end, the goal of studies such as this is to develop molecular approaches to identify the unique molecular abnormalities of each neoplasm. This project is part of a larger,

recent progression towards translational medicine, which has been described as “bench to bedside.” In other words, the goal of translational medicine is to develop scientific insights, which can then be used to systematically improve disease diagnosis and management. Dr. Coleman’s findings will ultimately improve patient care significantly for those with morphologically similar carcinomas of the head/neck and lung.

Keith Funkhouser ‘13 is undecided in his major

References

1. Interview with William B. Coleman, Ph.D. 9/23/09. 2. R.R. Mercer, et al. Exp. Mol. Pathol. 2008, 86, 1-9.

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Carolina Scientific

Network Science:

The Science of Connections Kevin Macon, Staff Writer & Amanda Traud, Guest Writer

n the Mathematics Department here at UNC there is a group of many undergraduate students, two graduate students, and one professor that all apply their mathematical skills to network science. Dr. Peter J. Mucha heads this group of many different majors who all have a thing for connections. College football teams to congressional committees--his research shows how network science, the study of interconnected systems called networks, can be applied in almost any context. One graduate student, Feng Shi, is currently working on applying what we know about networks to materials science, dealing with electric circuits and materials containing interacting nanotubes. Another graduate student, Amanda Traud, is currently working on two network projects. She is finishing a project started during her undergraduate career here at UNC analyzing Facebook networks [1]. She is also working to use network science as a way to better model the spread of HIV. Jennifer Dixon, a senior in Physics, is currently analyzing networks of interrelated proteins, drugs, and protein

domains to help predict potential drug targets. Noel Cody, a junior in Journalism and Information Science, is analyzing how the crowd influences movie ratings in a large set of Netflix movie rental data to study ``information cascades’’, a social phenomenon also referred to as a herding effect. Scott Powers, a senior in Mathematical and Decisional Sciences, is making comparisons across generation gaps in a network of baseball players from 1954 to 2008 [2]. Network Science is also being used to examine the community structure of voting on United Nations General Assembly (UNGA) resolutions in a project by Kevin Macon which will be described further. The visualization software used to make the illustrations for this article was previous project of Amanda Traud in collaboration with an undergraduate, Christi Frost, from Minnesota [3-4]. The first step in applying a Network Science analysis to a data set is to first define what we mean by a network. In the UNGA Resolutions, the networks were built as a collection of (nodes) countries connected by (edges) common votes on resolutions. We construct networks of UN member countries using available vote records on UNGA resolutions for sixty sessions (1946-2008) of voting in the UNGA [5]. One of the powerful tools in network science is community detection where the goal is to identify groups of nodes more interconnected with each other than nodes in other communities. For example, in Fig. 1, the two clusters in this graph illustrate the two relevant communities in the East (top right) - West (bottom left) division in the UN stemming from the Cold War. In this project, we use computational heuristics to find the communities that maximize a quality function called modularity. This quantity measures the number of connections within the communities relative to a null model of the expected background level of connections [6]. More elaborate details of this project have been focused on various ways of converting votes of yes, no, abstain to a connection

Figure 1: UN Member Countries in 1947 (Representative of 1946-1960) Each visualization color codes the countries geographically.

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Carolina Scientific with a length equal to that of the number of hops between them. For example, if the US is connected to England which is connected to France which is connected to Ireland, the US would have a spring of length three between itself and Ireland, one of length two between itself and France, and one of length one between itself and England. This algorithm moves the nodes around to get as close to a balanced spring system as possible. We used this algorithm to place the countries within their communities. By using both of these algorithms, we were able to respect the community structure in visualizing the network [34]. This research group uses network science in many areas including: epidemiology, material science, political science, social networks, sports, and information science. Having tools with widespread applicaFigure 2: UN Member Countries in 2005 (Representative of 1990-2008) Since the end of the Cold tions, this growing field connects people with diverse research interests. War the division in the United Nations is split more North-South (developed vs. developing countries) than The authors of this article and members of the rethe early Cold War East and West communities. Europe search group would like to acknowledge and thank and North America compose North. Dr. Peter J. Mucha and Dr. Mason A. Porter for their support as advisors in research projects in network strength (or edge weight) for analysis. Then for each science with funding by, SURF, AGEP, the associate network definition, it becomes a task to explore difprofessor support program in the college of arts and ferent null models. sciences, and an NSF grant DMS-0645369. Visualizing Networks To visualize these networks, we used a combination of two graphing algorithms, Fruchterman and Reingold and Kamada Kawai [7-8]. Fruchterman and Reingold is a graphing algorithm that takes in a network and puts repulsive forces between each node and every other node while also putting attractive forces between the sets of nodes that have edges between them [7]. For example if the US is connected to England but not France, there would be repulsive forces between the US and England and between the US and France, but there would be attractive forces only between the US and England. This algorithm moves the nodes, or countries in our case, around until the energy resulting from this system of forces is as close to zero as possible. We used this algorithm to place the communities of countries, by treating each community as a node and weighting the edges between communities by the number of edges between each community. Kamada Kawai is a graphing algorithm that takes in a network, and puts a spring between each node and every other node

Kevin Macon ‘10 is a Physics major

References

Amanda Traud is a graduate student in Mathematics

1. A. L. Traud, et al. arXiv. 2008 0809.0960. 2. S. Saavedra, et al. Physica A. 2009. 3. A.L. Traud, et al., Chaos. 2009, 19. 4. http://netwiki.amath.unc.edu/VisComms 5. E. Voten, et al., 2009. 6. M.A. Porter, et al. Not. Am. Math. Soc., 2009, 56, 10821097 & 1164-1166. 7. T.M.J. Fruchterman, et al. Software Pract. Exper., 1991, 21, 1129. 8. T. Kamada, et al. Inform. Process Lett. 1989, 31, 7. 9. Title image: Image produced with FoodWeb3D, written by R.J. Williams (www.foodwebs.org, Yoon et al. 2004).

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Cell Signaling Therapy -

Hope for a Seemingly Hopeless Cancer

Abby Bouchon, Staff Writer

dvancements in cell signaling therapy are allowing researchers to potentially defeat melanoma, the deadliest of all skin cancers. Melanoma develops in the cells which cause pigmentation; these melanocytes are mutated cells in the epidermis that form a nodule, a small aggregation of cells, that grows vertically until it invades the dermis [1]. Once melanoma has reached this stage, it can metastasize, or invade other parts of the body, through lymph nodes that circulate throughout the body (see Figure 1). On the other hand, basal and squamous cell

Figure 1. A picture of the skin. Melanoma develops in the melanocyte cells and grows vertically.

cancer is usually restricted to the uppermost skin layer and is treatable by surgical excision [2]. While melanoma is the least common skin cancer, with 95% of all skin cancer diagnoses being either basal or squamous cell, melanoma accounts for 79% of all skin cancer deaths. The dramatic percentage is due to the fact that malignant melanoma is not an easily treatable cancer—common treatments such as chemotherapy typically have low response rates [3]. Furthermore, melanoma is on the rise; the overall age-adjusted annual incidence of melanoma among young men (ages 15-39) went up from 4.7 cases per 100,000 persons in 1973 to 7.7 per 100,000 in

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2004. The overall rise among young women over the same period was much steeper, from 5.5 in 1973 to 13.9 in 2004 [4]. Due to the fact that melanoma metastasizes so quickly, it is difficult to surgically remove all tumors because the melanoma has often spread to internal organs. With all skin cancer on the rise, an alternative treatment is a necessity. Cell signaling pathways offer an exciting new treatment for malignant melanoma. Cell-to-cell communication is based off of cell signaling pathways, which are catalyzed proteins in a cell that alter cellular behavior. Different cell signaling pathways can instruct the cell to multiply, proliferate, or even commit apoptosis (cell death). To start this “snowball effect” however, a cell must receive a signal either from a cell physically next to it (juxtacrine signaling), a short distance away (paracrine signaling), or far away (endocrine signaling). While the methods vary, a signal comes in the form of a cell releasing a chemical transmission, such as a hormone, into the bloodstream to reach the designated cell recipients. Receptor ligands, a protein on the outside of a cell that is activated by a specific chemical signal, begin the reaction when the chemical signal binds to it. For instance, a skin growth hormone might be released by the brain into the bloodstream in order to signal cell proliferation, resulting in additional skin cells being created. The skin growth hormone would connect to the receptor ligand of a skin cell, which would then send a chemical signal cascading down a proliferation pathway. A mutation can make any cell cancerous, causing the cell to proliferate without waiting for a chemical signal to activate the cell signaling pathway. Ultraviolet rays are notorious for penetrating into skin cells and mutating DNA sequences, which can lead to deregulated cells that reproduce without activation. A recent study revealed that individuals that regularly use a tanning bed before the age of 35 increase their risk for melanoma by 75 percent [5].

Carolina Scientific Hope for malignant melanoma lies in the potential of disabling particular proteins in cell signaling pathways, therefore stopping cancerous cells from multiplying ceaselessly (see Figure 2). While cell signaling pathways are complex and very adaptable to protein inhibition, multi-drug treatment that disable several proteins at once is promising. This summer, I worked with Dr. Christi Augustine and Dr. Douglas Tyler at Duke University and studied the effects that three targeting agents had on cell lines with B-RAF and N-Ras protein mutation statuses. Research has

Melanoma by the Numbers

5% of all reported skin cancer is melanoma. 79% of skin cancer deaths is from melanoma. 7.7 annual melanoma incidence among men ages 15-39 in 2004 out of 100,000.

14.4 annual melanoma incidence among women ages 15-39 in 2004 out of 100,000.

75% increase risk for melanoma for individuals that regularly use a tanning bed before the ages of 35.

effective than Wortmanin or Rapamycin due to the fact that the drug specifically targeted the pathway the cancerous cell lines were using most. However, combinational therapy in which cell lines were simultaneously treated with Sorafenib and another drug might have proven to be equally successful with lower drug concentrations, lowering the adverse side effects on patients. With future research, the potential to learn more about which signaling pathways are most effective Figure 2. While melanoma is visible on the skin, it in inhibiting melanoma will increase, along with can quickly metastasize to other organs in the body. the possibility of finding an effective treatment. The future for cell signaling therapy looks bright shown that the Ras/RAF cell signaling pathways are as it continues to be developed to defeat malignant especially active in malignant melanoma, suggesting melanoma. that these pathways are more relied on by the cell as proliferation pathways [6, 7]. It was observed that Sorafenib, which targeted the Ras/RAF signaling pathway, was most effective in decreasing cell viability. All four cell lines tested had a mutation Abby Bouchon ‘13 within the Ras/RAF proteins, which suggests the is a Biology major cell line might rely more heavily on that signaling pathway (see Figure 3) [8]. Sorafenib was more Figure 3. Primary data from Sorafenib viability testing. As shown, at 20 µM Sorafenib successfully prevents the majority of cells from continuing to metastasize.

References

1. V. Liu, et. al. Surg. Clin. North. Am., 2003, 85, 31. 2. R.C. Martin, et. al. Cancer. 2000, 88, 1365. 3. T. Sinnberg et. al. J. Invest. Dermatol. 2009, 129, 15001515. 4. M. Purdue, et. al. J. Invest. Dermatol. 2008, 128, 29052908. 5. A. Green, et. al. Int. J. Cancer. 2006, 120, 1116-1122. 6. F. Meric-Bernstan, et al. J. Clin. Oncol. 2009, 27, 22782286. 7. J Ángel Fresno Vara et al. Cancer Treat. Rev. 2004, 30, 193-204. 8. A Russo et al. Int. J. Oncol. 2009, 34, 1481-1489.

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Carolina Scientific

Helping to Break the Habit: Naltrexone and Alcohol Dependency Mary La, Staff Writer

he search for effective pharmacotherapy to treat trexone were associated with family history, suggestaddictions to alcohol and other substances has ing genetic predisposition. Changes to the structure been an active area of research for the past few de- of µ-opioid receptors, another subclass of opioid recades. One of the main biochemical pathways stud- ceptors, were suspected in altering their functionalied in the development of these therapies involves ity. In particular, two single-base changes at separate the opioid receptors, which are also targeted by drugs locations in OPRM1, the gene that codes for this resuch as morphine. These receptors are concentrat- ceptor, have been intensively studied with respect to ed in the part of the brain responsible for emotions, their influence on alcohol dependency. Interestingly, hunger, and breaththere has been no link ing. The binding of a found between the specific class of neupolymorphisms (base rotransmitters called a) b) changes) and alcoendorphins to these hol/drug dependency, opioid receptors reeven though these sults in a euphoric base changes could feeling; for example, manifest different β-endorphins, a subaddiction treatment class of endorphins, outcomes for medicahave a stronger effect tions such as naltrexon the limbic sys- Figure 1: a) Naltrexone is a competitive inhibitor of a series one [3]. tem’s response than of opioid receptors [3]. b) Morphine. Compare the structural The Combined will morphine. A se- similarities between naltrexone and morphine. These similari- Pharmacotherapies ries of psychological ties allow naltrexone to competitively bind to the opiod recep- and Behavioral Intertors that morphine and related substances target. disorders, from adventions for Alcohol dictions to obsessiveDependence (COMcompulsive disorder, have been attributed to altera- BINE) Study sought to investigate the link between tions in this pathway [1]. Naltrexone (trade names these OPRM1 polymorphisms and response of paRevia, Depade, and Vivitrol) is one such medication tients with primary alcohol dependence to naltrexthat has resulted from addiction treatment research. one across two different therapeutic regimens. These Like other addiction treatment agents, this multi- were: ring, non-narcotic compound (see Figure 1) targets 1. medical management alone, which ina variety of opioid receptors and competitively included the dispensing of the naltrexone in hibits β-endorphins from binding to these receptors. addition to patient education that reviewed Though originally developed for treating addiction medication adherence and overall functo narcotics, naltrexone has found wider application tioning, and to the treatment of, among other disorders, alcohol2. medical management with combined beism [2]. havioral intervention, which added “cogni While naltrexone initially found success in fative behavior therapy, 12-step facilitation, cilitating treatment of alcohol addiction, it was soon motivational interviewing, and support found that not all patients responded to treatment system involvement” to the medical manequally. As early as 1996, different responses to nalagement regimen. [4]

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Carolina Scientific

Figure 2. 3-D representation of Naltrexone.

The double-blinded study (in which neither the investigator nor the subject knew who was in the experimental and control groups) was coordinated through the Collaborative Studies Coordinating Center at UNC, with patients being recruited and treated at eleven other academic sites across the U.S. [5] The treatment period lasted for sixteen weeks, during which study participants were evaluated on alcohol consumption and craving after having been administered naltrexone or a placebo. The participants had to meet the DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) definition of primary alcohol dependency; the DSM-IV characterizes substance dependence by the following: 1. Tolerance to the substance. 2. Withdrawal when substance is not taken for a long time. 3. Substance is taken in excess, or over longer period than intended. 4. Attempts to control substance use are unsuccessful. 5. Large time investment in obtaining, using, and recovering from substance use. 6. Substance use has a detrimental effect to daily life (social, occupational, etc.). 7. Continued substance use even if the patient is aware that the substance causes physical or psychological harm. [6] Study participants had to have abstained from alcohol for 4-21 days before randomization. They also had to have had more than 14 drinks (women) or 21 drinks (men) per week, with at least 2 heavy drinking days (defined as ≥ 4 drinks/day for women and

≥ 5 drinks/day for men) during a consecutive 30-day period within the 90 days prior to baseline evaluation [5]. In the 604 participants included in the pharmacogenetic analysis, it was concluded that patients who had a copy of a specific one of the polymorphisms mentioned above exhibited better naltrexone response and improvement in decreasing alcohol dependency [4]. It is important to remember that naltrexone is not the magic bullet that can completely and permanently resolve alcohol dependency, which is a complex disorder. The clinical results observed are applicable for the sixteen-week study period, but whether these outcomes are maintained in the long run, or when therapy is discontinued is still unknown. However, the information gleaned from this study and other comparable investigations can be used to tailor courses of therapy for patients suffering from addictions to alcohol or other substances, or even other psychological disorders, which could lead to better treatment outcomes. However, much is not known about the influence of other beneficial therapies on the efficacy of naltrexone, or about the pharmacogenomics of other medications used to treat similar disorders in general, and this field of research should remain of high interest for years to come.

Mary La ‘11 is a Chemistry and Computer Science double major with a Spanish minor

References

1. T. Scheve. “What are endorphins?”, 2009, <http://health. howstuffworks.com/human-nature/emotions/happiness/science/endorphins.htm> 2. J.R. Volpicelli, et. al. Arch Gen Psychiatry, 1992, 49, 876880. 3. D.W. Oslin, et. al. Neuropsychopharmacology, 2003, 28, 1546-1552. 4. R.F. Anton, et. al. Arch Gen Psychiatry, 2008, 65, 135-144. 5. Email with David Couper, Ph.D. 10/28/09. 6. “Alcohol Abuse and Dependence - Diagnosis.” 2001, <http://www.mentalhealthchannel.net/alcohol/diagnosis. shtml>.

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Carolina Scientific

BPA: promoting aggressive behavior in young girls Rebecca Searles, Staff Writer

midst a sea of rumors ing scales from teacher and about harmful chemiparent reports. cals leaching into our Na Nearly 99 percent of lgenes, and stainless-steel the women had at least water bottles becoming one urine sample that conthe new fad, skeptics now tained some amount of have concrete evidence to BPA. Daughters of mothturn to. A recent study coners with the highest BPA ducted in part by UNC’s levels were more likely Gillings School of Global to have high aggression Credit: http://www.goodhealth.com/articles/2007/08/06/nutriPublic Health has found a scores, similar to those of tion_for_young_athletes_fueling_up_before_the_game link between Bisphenol A a boy. The association was (BPA), a common pollutant in plastics, and adverse even stronger when high BPA exposure was seen earbehavioral effects on young girls. Researchers found lier in pregnancy [3]. that daughters of women who were exposed to high BPA is an estrogen-like chemical that is commonlevels of BPA during their pregnancy expressed more ly used in the production of polycarbonate plastics hyperactive and violent behaviors in early childhood and exposy resins. This includes the production of [1]. some types of plastic water bottles, canned food lin The study, published in Environmental Health ings, water pipes, infant bottles, and medical tubing. Perspectives on Oct.6, was conducted by researchers Human exposure to this substance is thought to come from a myriad of universities, including UNC, Simon through the diet when it leaches into food and drinks Fraser University in Vancouver, B.C., and University through these containers [3]. According to the Cenof Cincinnati. Urine samples were collected from ters for Disease Control and Prevention, about 93 249 pregnant women in Cincinnati, OH, at staggered percent of Americans have detectible levels of BPA intervals during their pregnancies. Researchers mea- in their urine [1]. sured BPA concentrations in each sample, and then The new findings are consistent with previous assessed the children for behavioral problems when studies with mice that found that BPA caused adthey turned 2 years old, using the Behavioral As- verse neurodevelopmental effects on newborns and sessment System for Children-2 (BASC-2)[1]. This fetuses, as well as more aggressive offspring. commonly-used analytical tool relies mostly on rat- “We wanted to know if there was a risk in humans

Figure 2. The molecular structure of Bisphenol A (BPA).

Figure 1. The molecular structure of an estrogen.

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Carolina Scientific “In the developing brain, timing is everything,” said neuropsychiatrist Louann Brizendine, author of The Female Brain. “I’m worried that tiny amounts of this stuff, given at just the wrong time, could partly masculinize the female brain” [4]. Boys’ behavior did not seem to be affected by BPA concentration, although there was some evidence of “increased internalizing scores” (depression, anxiety, and social withdrawal) among these boys. Researchers are unsure why there is discrepancy between boys’ and girls’ reactions to BPA exposure [1]. Many government agencies in the U.S. and Canada have expressed concern about the effects of BPA exposure, particularly in children. In Canada, baby bottles and other baby products containing BPA have been banned [1]. Some representatives of the chemiCredit: http://www.backcountrygear.com/catalog/accessdetail.cfm/NA1007 cals industry argue that the study is not thorough enough to sound alarm bells in the public, and that In 2008, Nalgene, a plastics company that sells water other factors may be at work in contributing to the bottles, launched the “Everyday” line, which features a girls’ aggressive behaviors [2]. The FDA’s report on number of containers made from materials that do not BPA’s safety is expected to be released in November contain BPA. [4]. Currently there are no requirements that BPA be for neurodevelopmental problems,” said the lead au- listed on product labels, so it is difficult for consumthor of the study, Joe Braun, a doctoral student of ep- ers to avoid. However, one way to know, Braun says, idemiology at UNC Gillings School of Global Public is to check for plastics with the number 7 or 3 in Health. “Study results indicate that exposure to BPA the recycling symbol. These products are a known early in the pregnancy seems to be the most critical source of BPA [2]. issue. The most damaging exposure might happen before a woman even knows she’s pregnant” [1]. Researchers believe BPA may be linked to boyish “externalizing behavior,” (aggression, hyperactivity, Rebecca Searles anti-social activity) because of its estrogen-mimick‘11 is a Biology and ing properties. Although estrogen is more promiPsychology double major nently a “female hormone,” it acts the opposite to the newly developing male brain. Around the 11th or 12th weeks of pregnancy, estrogen actually serves to masculinize the male brain. a. b.

References

Figure 3. Some type 7 (a) and type 3 (b) plastics bearing these symbols may leach BPA.

1. P. Lane. “Prenatal exposure to BPA might explain aggressive behavior in some 2-year-old girls,” 2009, <http://uncnews.unc.edu/content/view/2944/107/>. 2. “Plastics chemical tied to aggression in young girls,” 2009, < http://www.nlm.nih.gov/medlineplus/news/fullstory_90252. html>. 3. J.M. Braun, et al. Environmental Health Perspectives. 2009. 4. L. Szabo. “Plastic chemical linked to aggression in toddler girls,” 2009, < http://www.usatoday.com/news/health/200910-06-bpa-pregnancy_N.htm>.

Fall 2009, Volume II Issue I

Carolina Scientific

A nervous development:

from neural tube to nervous system Amy Abramowitz, Staff Writer

he development of a single zygote into an organism with a brain is a process that has captivated scientists for centuries. One of these scientists is Dr. Andrew Lumsden, the director of the Medical Research Council (MRC) Centre for Developmental Neurobiology in London. The Center was created as a partnership between the MRC, which is comparable to the National Science Foundation in the US, and King’s College in London. The Center’s 140 scientists and staff are all dedicated to deciphering how the early stages of the brain develop. This summer I had the opportunity to work in Dr. Lumsden’s lab and learn about his research into the development of the chick brain.

Dr. Andrew Lumsden

There are three layers of a vertebrate embryo- the ectoderm, mesoderm, and endoderm. The ectoderm is the outermost layer which eventually becomes the nervous system. The first step in the de

Fall 2009, Volume II Issue I

Credit: Nature

Formation of the neural tube from the ectoderm. The neural tube eventually becomes the brain and spinal cord.

velopment of the nervous system is a molecular signal from the mesoderm to the ectoderm inducing the neural plate. The neural plate folds to become the neural tube, which eventually becomes the brain and spinal cord [1]. More signals cause the neural tube to develop an anterior-posterior axis. The anterior side is where the forebrain is located and the posterior side is where the spinal cord is located [2]. The specific structures in the brain develop from signaling centers as seen in the diagram. These are strips or compartments of cells that send signals to surrounding regions and induce a certain brain area to form. Dr. Lumsden has focused his research on these signaling centers. His early work was on rhombomeres, eight segments that make up the early hindbrain. These structures had been identified in invertebrates, but little was known about their function. Dr.

Lumsden studied the chick embryo and noticed the same swellings and constrictions in the chick hindbrain [2]. The first part of Dr. Lumsden’s investigation into rhombomeres involved injecting ink into the cranial nerves of chick embryos during development. He noticed that the cranial nerves could be traced back to rhombomeres 2, 4, and 6 in the developing hindbrain. Next, he used various immunohistochemical techniques to identify where specific proteins were in each rhombomere. He found that there was an orderly pattern where each rhombomere produced different proteins [3]. It was also discovered that in each rhombomere, HOX genes, the genes responsible for the structural development of an organism, are expressed differently [2]. One of Lumsden’s key discoveries about hindbrain development was that rhombomeres are

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Figure 1. In a side view of an embryonic avian brian, rhombomeres (r1-r7) and the boundary between midbrain and hindbrain (MHB) can be seen.

lineage-restricted compartments where cells in one compartment do not migrate into another compartment. He used a technique called microiontophoresis where a charged dye is injected and gives a single cell a fluorescent marker, allowing divisions of this single cell can be observed. Dr. Lumsden found that when a single cell in a rhombomere divides, that cell and clones of it all stay in the same rhombomere. Using axon tracing he saw that each rhombomere develops into a different part of the hindbrain. Also each rhombomere develops motor neurons that innervate a unique part of the body [3]. More recently, Lumsden’s group has begun to study the boundaries in the developing forebrain using many of the same methods he used to study the hindbrain. In particular, he has studied one structure that lies between the thalamus and prethalamus called the zona limitans intrathalamica (ZLI) that is actually a compartment itself. The ZLI, as seen in Figure 2, is involved in the development of the thalamus and prethalamus, the structures surrounding it. As opposed to the rhombomeres where different genes are expressed, the ZLI secretes one signal- sonic hedgehog,

a protein that acts on cells to form the thalamus and prethalamus. There is more sonic hedgehog released in the areas bordering the ZLI and less reaches areas further away from the ZLI. The relative quantity of sonic hedgehog leads to different areas within the thalamus and prethalamus [2].

the gene is overexpressed. This is done by opening the egg and injecting the DNA and a protein that produces a fluorescent signal into the embryo and then applying an electrical signal so that the cells in the embryo open and incorporate the new DNA. The egg is then sealed and the embryo is allowed to develop in order to see how the new DNA affects its growth. This is useful in determining the function of the gene. In the future, Dr. Lumsden hopes to continue his research on the development of the nervous system and work toward application of his research to stem cell therapies. An understanding of the signals that cause certain cells to develop into motor neurons may be useful for controlling what kind of cell a stem cell becomes and controlling which part of the body it innervates. This kind of treatment could be very beneficial for people with medical problems including Parkinson’s disease.

Figure 2. The ZLI can be seen in green.

This summer I was able to learn two of the techniques used by the Lumsden lab in the study of the forebrain. The first technique, in situ hybridization uses a RNA probe which is a strand of complementary RNA to the cell of interest. The probe binds to the gene of interest when annealed at the appropriate temperature and then a fluorescent marker can be applied to visualize where the gene is located. In ovo electroporation procedure allows the phenotype of the embryo to be seen when

Amy Abramowitz ‘11 is a Psychology major with a double minor in Biology and Chemistry

References

1. Scott F. Gilbert, in Developmental Biology (Sinauer Associates, 2003). 2. Interview with Andrew Lumsden, Ph.D. 7/29/09. 3. C. Kiecker, et al. Nature Reviews Neuroscience, 2005, 6, 553-564.

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Carolina Scientific

Keeping the Beat Ranjan Banerjee, Staff Writer

ucus. Gross, right? I know you probably cringe when you think about all those gooey chunks of slime that you feel in your throat after coming in from an especially nippy fall day. I agree with you. But if it were not for mucus we would have far greater problems to deal with than grossing yourself out. Why is mucus there in the first place? It is most important function from a medical standpoint is entrapment of foreign bodies such as viruses and bacteria, to protect the respiratory system. Once these foreign particles get caught in the mucus, they are ejected from the body by coughing and sneezing. But simply coughing isn’t sufficient to clear mucus from the lungs (if it were, you would be coughing up many other things as well); the mucus has to be able to move

by some other mechanism. This is where cilia come into the picture. Cilia are long, thin organelles that are made up of microtubules. What makes them interesting is the fact that they have the ability to beat back and forth regularly, on their own [2]. Millions of cilia line the respiratory tract, and their beating motion moves the mucus that lies above them. According to Dr. Superfine, the cilia are like taking ‘oars on a Roman galleon, putting them on the bottom of the river with the oars pointing up, and that’s what going to make the river flow’ [1]. It is this interaction between the cilia and the overlaying mucus that the Superfine lab studies. In the context of this research, there are two types of fluid. The first type is the viscous fluid, which consist of fluids like water,

Figure 1: Ciliated cells (outlined in black) are important in the transport of mucus, which is produced in goblet cells.

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Professor Richard Superfine

ethanol, and orange juice; basically any fluid that pours well. We know a lot about the physical properties of these types of fluids; how they move, etc. What we do not know a lot about are the viscoelastic fluids. These are fluids that behave both like a solid and a liquid; they ‘push back’ when stress is applied to them, and regain their shapes after the stress is removed. Another important property of this type of fluid is that the faster you hit it, the more stiff it is. I’m sure you have seen what water and cornstarch do together; if you tap it quickly with your finger, it’s like tapping a solid object. However, if you press down slowly, your finger sinks in like it was a liquid. Mucus is a visco-elastic fluid [3]. Also, the cilia itself does not have a static stiffness; it can be either hard or soft depending on environmental conditions. As you can imagine, these properties of the cilia and mucus makes analysis and modeling extremely difficult. Neverthe-

Carolina Scientific less, understanding these properties is essential to understanding the causes and treatment of many diseases. Many departments at UNC are involved in understanding these properties, including the biology, math, physics, and computer science departments. This collaborative is termed the Virtual Lung Project. So how does one go about studying cilia beating? By making models. In the Superfine lab, these models are made from silicone polymers, mixed with iron filings. The mixture is poured into a mold that is shaped like a bed of cilia. Once the molding process is over, the result is a bed of cilia-like protrusions. Because they have iron filings in them, they can be moved by magnets to simulate beating. The physical properties of the model cilia, such as length and stiffness, are changeable, so many different conditions can be simulated. By studying these models in the lab, researchers can get a good idea of what types of forces act on the cilia and mucus, and how mucus movement occurs. From these

Figure 3. Schematic diagram of the structure of cilia, which are made of microtubules (shown as green circles in the diagram).

laboratory results, inferences can be made about how the system operates in the body, which in turn leads to insights on mucus clearance. While this research might sound highly specific, its implications and applications are vast. Several debilitating conditions, such as cystic fibrosis have defective cilia or mucus as their cause [3]. In addition, cilia are present in many

other locations in the body, such as the intestines and reproductive organs. By understanding the physical environment and properties of cilia, we can begin to understand both the causes and treatments of these relevant diseases. Through the work done in Dr. Superfine’s lab and the Virtual Lung project, this ideal is becoming a reality.

Credit: WebMD

Ranjan Banerjee ‘12 is a Biology and Physics double major

References

Figure 2. Cilia, hair-like structures, have the ability to beat back and forth, moving mucus in the respiratory tract.

1. Interview with Richard Superfine, Ph.D. 9/30/09. 2. I. Ibanez-Tallon, et. al. Hum. Mol. Gen. 2003, 12, R27-R35. 3. M. King. Pediatr. Res. 1981, 15, 120122.

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Carolina Scientific

A Scientific Callin': Probing Deeper into Colon Cancer Frank Mu, Staff Writer

he word “colonoscoalong the adenoma-carcinoma sequence, through acpy” often forms the cumulation of multiple mutations [2]. base of many jokes and Once normal colon cells undergo a malignant can bring out the rawest transformation, a tumor of cancer cells may develop. of emotions from even By this time cancer cells have acquired many capamentally tough individubilities that allow it to evade many of the regulations als. But the bottom line governing normal cell proliferation and homeostais that colonoscopies sis [3]. Often times, uncontrolled cell division leads are necessary:colorectal to invasive colon cancer cells. Some may enter the cancer is the second blood stream, metastasize or spread to another part leading cause of canof the body, and begin forming another tumor. Mulcer-related deaths in tiple tumors can quickly use up surrounding nutriDr. John Lynch is the the United States and ents and disrupt the normal function of neighboring Assistant Director of the the third worldwide [1]. cells [3]. And since cancer cells evade apoptosis, cell Undergraduate Student Over the past summer, death,they contain limitless replicative potential by Scholars Program at the I worked in Dr. John mimicking signals that control proliferation pathLynch’s lab at the Uni- University of Pennsylvania ways [4]. In order to combat colorectal cancer it beversity of Pennsylvania, helping to elucidate the pro- comes important to understand the pathways behind cess of how many colon cancers arise from the nor- proliferation of normal intestine. mal epithelial tissue lining human intestines. One area of particular interest is the Wnt/β-catenin/ The source of colorectal cancers comes from TCF pathway (Figure 2), an important pathway leadthe initial development of benign precursor lesions ing to proliferation and differentiation of normal (most commonly known as “polyps”) called adeno- colonic epithelium [2]. After the Wnt membrane mas in the colon [2]. As mutations accumulate in surface receptor is activated, a series of protein acthe cell, the polyps begin to form and at first are generally innocuous. Progression along the adenoma-carcinoma sequence (Figure 1) describes the string of mutations required to overcome cell regulation [2]. Since the proliferation of each cell is regulated by several tumor suppressor genes, a few mutations may loosen proliferation restrictions, but does not result in uncontrolled cell division. In order for a cancerous tumor to form, there Figure 1. The adenoma carcinoma sequence with initial polyp formation and must be further progression progression to a malignant tumor [2].

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Carolina Scientific tivations and interactions leads to stabilization and buildup of a protein called β-catenin in the cytoplasm. Eventually, this protein moves into the nucleus, where it interacts with another protein, the TCF/ LEF family member, to bind DNA and begin transcription of certain target genes. Normal activation of these genes informs the cell to proliferate and divide [5]. Mutations in the Wnt/β-catenin/TCF pathFigure 2. The activation of Wnt pathway when Wnt protein binds to way can result in constant membrane receptor. Mutations can cause the pathway to continuously be high intracellular levels active, though Wnt protein is absent [2]. of β-catenin and constant stimulation of genes that start cell proliferation [3]. tant role in many other model organisms in addition As a result, the pathway is always on, leading to un- to humans [5]. Recent focus is directed at how Cdx2 controlled target gene expression, a common event interacts with β-catenin in the nucleus. Cdx2 has in human colonic cancers. Though over-expression been shown to bind to β-catenin (Figure 3), thereby in the Wnt/β-catenin/TCF pathway leads to ma- disrupting the β-catenin/TCF protein complex and lignant transformation, completely inhibiting the inhibiting β-catenin/TCF transcriptional activity [5]. Wnt/β-catenin/TCF pathway is implausible: under- However, the mechanism by which Cdx2 attaches to expression of the pathway results in malformation of β-catenin is still unknown. Undoubtedly, fully underthe intestinal crypts required for absorbing nutrients standing how Cdx2 plays a role regulating β-catenin/ [3]. Much of the focus of my summer has been deter- TCF transcriptional activity has important implicamining how this pathway is normally constrained in tions in the field. regular intestine. ~ Special acknowledgements to the Lynch lab and USSP One important factor promoting differentiation and regulating proliferation is the homeodomain protein Cdx2 [5]. This protein is found to play an imporFrank Mu ‘12 is a Biology and Economics double major

References

Figure 3. The binding of Cdx2 to β-catenin/TCF regulates colorectal cell proliferation [5].

1. S.R. Hegde, et. al. Expert Rev. Gastroenterol. Hepatol. 2008, 2, 135-149. 2. L. Ricci-Vitiani, et. al. Gut. 2008, 57, 538–548. 3. J.P. Lynch et al, in Physiology of the Gastrointestinal (Elsevier, 2006). 4. A.R. Sepulveda et. al, in Cancer Genome and Tumor Microenvironment (Springer, 2009). 5. R.J. Guo et al. J. Biol. Chem. 2004, 279, 865-875.

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Carolina Scientific

Reproductive Immunity:

Toll-like Receptors in the Human Endometrium Vahini Chundi, Staff Writer

hat differentiates a pathogen, a transplanted tissue, and an embryo from one another? All are composed of foreign cells, but the immune system kills pathogens or rejects transplanted tissue, while accepting the growing fetus. How is this possible? What gives our bodies the ability to pick and choose? These may seem like trivial questions, but at the microscopic level it is a complex aspect of nature that cannot be easily explained. The first answer to these questions was found as early as the 1940’s by Sir Peter Brian Medawar and Sir Frank Macfarlane Burnet in England. At the time Medawar and Burnet were conducting pioneering organ transplant research which led them to believe that a

certain mechanism which differentiates a cell of the body from a pathogen must be present in our bodies [4]. Though they did not know the exact nature of the mechanism or the way it functioned they laid the foundation to transplant immunology. Their insights led them to an obvious question, why weren’t babies rejected like the transplants? This question introduced a fascinating new line of research: reproductive immunology. Reproductive immunology is the study of how the body maintains immunity during reproduction and pregnancy, but avoids attacking the fetus. Dr. Steven L. Young, reproductive endocrinologist and associate professor at UNC School of Medicine, currently studies how

Figure 1. TLR receptors found in the human body.

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Steven L. Young, M.D., Ph.D, Associate Professor at UNC School of Medicine

innate immunity (a branch of immunology that uses receptors encoded from the germ line) of the endometrium prevents an immune response from occurring during embryo implantation [1]. The endometrium is the inner lining of the uterine wall, comprising 10% of the mass of the uterus and it is the surface into which the embryo implants. It is also the tissue which is shed during menstruation. The endometrial epithelium is the uppermost layer of the endometrium, which in turn, makes it the first to encounter pathogens or embryos. Due to its location, glandular epithelium is vulnerable to pathogens such as herpes simplex virus (HSV), cytomegalovirus (CMV), and human immunodeficiency virus (HIV) [4]. Thus it is critical for the endometrium to serve a dual function of protecting the reproductive tract from pathogens, while at the same time allowing implantation

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Figure 2. Endometrial lining.

of the embryo. Dr. Young and his team believe that this dual-function is done via an innate immune response in the epithelium using toll-like receptors (TLR). Tolllike receptors are leucine repeats with pattern recognition receptors (PRR) that allow them to identify pathogens. Toll-like receptors in turn produce cytokines which regulate epithelial proliferation, protect the immunity of tissue, and aid in embryo implantation [1]. Currently there are ten known tolllike receptors (TLR 1-10) which target a wide variety of pathogens such as parasites, fungi, bacteria, and viruses [3]. In addition to this Dr. Young and his team were the first to find TLR expression in the endometrium Dr. Young searched for the expression of TLR mRNA using separated endometrial epithelial cells, stroma, and total endometrium. The purity of each sample was first tested using cytokeratin and vimentin immunostaining. Then a common laboratory tech-

nique, real time PCR, was used to test for the presence of TLR. Results indicated that TLR1-6 and 9 were expressed in endometrium, while TLR 7, 8, and 10 were not expressed. These results suggest that TLR functions as an innate pathogen detector in the endometrial epithelium [3]. Currently, Dr. Young and his team are extensively studying the implications of TLR3 based on the uterine cycle and hormonal levels. TLR3 has been found to alternate from high to low levels during the secretory and proliferative phases of the menstrual cycle, respectively. The high levels of TLR3 during the secretory phase (the last 14 days of the menstrual cycle during which embryo implantation occurs) suggest that TLR3 maybe involved in receptivity to embryo implantation. Furthermore, progesterone (a hormone involved in embryo implantation) levels are highest during the secretory phase of menstruation. Dr. Young believes that progesterone may

stimulate TLR3 expression. The increase in TLR3 may be important for embryo surival, since it helps to detect viruses and stimulate anti-viral immune responses. The way TLR3 detects viruses is by recognizing dsRNA (doublestranded RNA), which occurs during replication of most viruses [2]. Interestingly, Dr. Young has hypothesized that TLR3 also plays a role in embryo implantation. Thus the increase in endometrial TLR3 during the time of embryo implantation may play a dual role. Dr. Young’s work with toll-like receptors in the endometrium has been important not only to the field of reproductive immunology, but to all of reproductive science. By understanding the role of tolllike receptors as protective agents, science has the potential to make many advances such as preventing miscarriages, making in-vitro fertilization more successful, treating or preventing endometriosis, and even help to explain infertility in women [4].

Vahini Chundi ‘11 is a Biology and Psychology double major with a Chemistry minor

References

1. Interview with Steven Young, M.D., Ph.D. 2/10/08. 2. I. Mackay, et al. New Engl. J. Med. 2009, 343, 338-344. 3. S.L Young, et al. Am. J. Reprod. Immunol. 2004, 52, 67-73. 4. R.L Jorgenson, et al. Hum. Immuno. 2005, 66, 469-482.

Fall 2009, Volume II Issue I

Carolina Scientific

Arsenic in Drinking Water? A Dietary Approach to Improving Arsenic-Induced Diabetes Jesse Lomas, Staff Writer

rink more water. That’s what people are always telling us to do. Being hydrated will prevent you from getting headaches and feeling lethargic. It will help you perform better in sports, speed the rate at which you digest food and burn fat, cushion your joints, and regulate your body temperature. It can even make your skin plump and radiant [1]. With all of that coming from the mere consumption of a simple compound, you would think this is too good to be true. Unfortunately, you may be right in some cases. Drinking water supplies can sometimes be contaminated by pathogens, pesticides, trace elements and many other impurities which result in a not-so-pure compound with some not-so-beneficial results. One such trace element impurity, inorganic arsenic, poses the risk for a multitude of cancers, cardiovascu-

lar diseases, skin disorders and recently investigated at UNC, diabetes mellitus [2]. Currently, the link between diabetes and arsenic consumption is under extensive research led by UNC research associate professor of toxicology and nutrition, Miroslav Styblo, Ph.D., both at UNC and abroad [3]. After finding a correlation between arsenic consumption and the onset of diabetes, Professor Styblo has been conducting laboratory and population-based research in order to better understand this disease’s mechanism and how it affects human health. While ideally, filters would be applied to all drinking water sources to prevent arsenic-induced health complications, this process would be nearly impossible due to the scattered exposed populations and economic and cultural barriers. Alternatively, Dr. Styblo’s research seeks to achieve a more feasible way to

Figure 1. Map of the arsenic concentration in drinking water in the U.S.

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reduce the negative health effects. With his on-campus lab, recently named the newest Gillings Innovation Laboratory at UNC, Dr. Styblo aims to study the significance and effects of arsenic in its various metabolic forms on human cells and tissues. In the past, population studies have suggested that humans exposed to the same levels of arsenic are affected in different ways with varying intensities. It is believed that individuals’ unique metabolism of arsenic may be the cause. From information gained on the absorption and digestion of arsenic and previous knowledge of these processes for various foods, Dr. Styblo hopes to develop a specialized diet for at-risk populations that will interfere with the mechanism by which arsenic triggers the development of diabetes and other health problems. Similarly, in collaboration with assistant professor of nutrition, Dr. Zuzana Drobna, he has found that a modified diet, when combined with arsenic-based cancer treatment, may improve the efficiency by which arsenic kills leukemia cells [3]. This inspires an optimistic outlook for the possibility that a controlled diet may decrease the intensity of arsenics negative effects as well. How and Where are People at Risk? According to the World Health Organization, over 130 million

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Figure 2. Map of Bangladesh.

people in the world are exposed to arsenic in their drinking water, but considering the limited data available, the actual number of those at risk could much higher. Arsenic is the 20th most common element in the earth’s crust, the most potent carcinogen and enters drinking water sources from the dissolution of metal ores and erosion of bedrock. Arsenic is also released into the atmosphere as a product of fossil fuel combustion [4]. Argentina, Australia, Bangladesh, Chile, China, Hungary, India, Mexico, Peru, Thailand, and the United States are among those affected by contamination above the EPA (En-

vironmental Protection Agency)’s [6]. Previous research at UNC has suggested safe limit [2]. pinpointed the specific step in the cascade of signaling that prevents Did you know? glucose uptake in this specific In Bangladesh, arsenic was in- type of diabetes and now tests troduced to the drinking water in are being done to investigate how the 1970s when the UN drilled diet-induced obesity and arsenictube wells to provide a “clean” induced diabetes may affect each drinking water alternative to the other [3]. Results from lab tests prevalent use of surface water on mice have shown that arsenic which contained parasites and blocks obesity in mice but still rebacteria. However, the wells were sult in glucose intolerance from drilled into bedrock in which ar- a source other than insulin resissenic was present in high concen- tance. Information from lab retration [3]. In order to hide this search is being translated to popuembarrassing oversight, doctors lation studies in Mexico, where it hid the results of tests from people is hypothesized that human obewith arsenic poisoning [5]. sity and exposure to arsenic has synergistic effects that result in Translational Research: more severe cases of diabetes [6]. From the Lab to the People. Recent and ongoing research investigating the mechanism of arsenic-induced diabetes mellitus has revealed that this form of diabetes acts differently than typical type II diabetes that is common in adults. In contrast with type II diabetes which is caused when the human body is resistant to insulin’s signal to take up glucose Jesse Lomas ‘12 is a Public Healthfrom the blood, arsenic-induced Nutrition major with a double minor in Music and Spanish diabetes mellitus causes glucose intolerance by different means References Credit: UCSF

Figure 3. Mechanism of insulin resistance in people with normal type II diabetes.

1. M. Silence. “Top 4 Benefits of Drinking Water,” 2006, <http://www. thedietchannel.com/Top-4-Benefits-ofDrinking-Water.htm>. 2. “Arsenic in Drinking Water,” 2001, <http://www.who.int/mediacentre/factsheets/fs210/en/>. 3. Interview with Miroslav Styblo, Ph.D. 09/29/09. 4. “Arsenic in Drinking Water,” 2007, <http://www.epa.gov/safewater/arsenic/ basicinformation.html>. 5. F. Pearce. “Bangladesh’s arsenic poisoning: who is to blame?” 2001, <http:// www.unesco.org/courier/2001_01/uk/ planet.htm>. 6. Email with Miroslav Styblo, Ph.D. 10/12/09.

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Carolina Scientific

TheHistoneCodeHypothesis Prashant Angara, Staff Writer

he 20th century was filled with breakthroughs in the field of genetics. In 1953, Francis Crick and James Watson published their historic paper describing the structure of DNA. In 1961, Marshall Nirenberg cracked the genetic code, showing that DNA is translated in triplet pairs. And in 2000, the human genome project was completed, leading to the 2001 publication of the human genome sequence [1]. Yet, for all these major discoveries, we still do not know the full details on how the exact same DNA in all our cells is expressed so differently across our bodies. What causes our nerve cells to be different from our muscle cells? Or even more importantly, why are certain genes over-expressed in cancer cells but not in normal cells? There are many possible hypotheses, but Dr. Brian Strahl of the UNC School of Medicine offers one possible explanation.

Figure 1. In the first level of packing, DNA is coiled around histone proteins (yellow-green). Histone H1 (pink) acts as a spacer between nucleosomes.[5]

Dr. Strahl is one of the pioneers of the histone code hypothesis that offers one explanation on how genes are regulated [2]. The histone code hypothesis states that combinatorial patterns of histone modifications results in different expressions of DNA [2]. So what exactly does this mean? In eukaryotic cells, the amount of DNA far exceeds the available space in the cell. In human cells, for example, there is about 6 feet of DNA per cell. In order to package the genetic blueprint into a single cell, DNA is wrapped around proteins known as histones. To put it in perspective, the amount of DNA packaged tightly into the cell is the equivalent of taking 5 miles worth of string and fitting it into an area the size of a pencil tip [3]. However, the DNA must still be accessible so the information can be expressed into proteins. Here, histones play a key role. Dr. Brian Strahl, Associate Professor DNA is coiled around the nucleoat UNC School of Medicine

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some core particle (see Figure 1), made up of eight histone proteins. Because these histones are largely positively charged proteins, the very negatively charged DNA is attracted to them. By breaking apart this histone-DNA interaction or other histone-histone interactions, DNA is accessed for gene expression. This begs the question how exactly are these complexes dissociated? Histones are not static proteins. Modification to different amino acids on the histones causes the configuration and charge density of histones to change such that the histone-DNA interaction gets weaker or stronger. For example, adding an acetyl group (-COCH3) to histones (known as histone acetylation) has been shown to relax this coiling of DNA around histones, while some phosphorylation (addition of a -PO4 group) has been associated with coiling of DNA during mitosis [2]. These

Carolina Scientific histone modifications are the key to the histone code hypothesis [4]. The histone code hypothesis can be thought of as being analogous to the genetic code [2]. The genetic code states the DNA is translated in three base pair units (codons) and different combinations of these base pairs result in different amino acids. Similarly, the histone code hypothesis states that patterns of histone modifications result in different expressions of the genes in DNA [2]. For example, if a histone was modified in specific places, then a specific protein that recognizes those modifications would then interact, thereby causing a change in biological and/or DNA function (see Figure 1). Figure 2 shows some examples of modifications on various histone tails. How exactly do we know that this is a valid hypothesis? Present research points toward this hypothesis being a valid one. For example, consider the phosphorylation of histones. Histone phosphorylation, because it adds a negative charge, causes decondensation of chromatin (unwinding DNA). However, a specific phosphorylation is also required for the condensation of chromatin (winding up DNA) needed during mitosis [2]. How is it possible that phosphorylation condenses and decondenses DNA then? One answer is that this histone modification does not function alone; rather, multiple histone modifications act in combination to specify function. This hypothesis also provides an explanation for exceptions to general histone modification rules [2]. For example, acetylation is generally related with gene activation, but studies

Figure 2. Histone modifications occur at selected residues and some of the patterns shown have been closely linked to a biological event (for example, acetylation and transcription) [2].

in multiple organisms have shown that acetylation is also involved in transcription repression, functioning in a completely opposite role. Silent loci in yeast have also been shown to be marked with acetylation. However, if a code is being read, rather than single modifications, it is possible that distinct enzymes act on the combinatorial sequence of modifications. With any research, there is always the question of why is this important? Why is it so important that we decipher the histone code? The answer lies in the vast possibilities in the fields of medicine if this code is deciphered. Defects in histone-modifying enzymes have been linked to cancer, aging, neurodegeneration, drug addiction, viral latency, and stem cell biology [2]. Understanding this code also gives a fundamental insight into how DNA is regulated, a very important question in molecular biology today. With this in mind, the Strahl lab is currently trying to test this hypothesis. The method involves creating a large library of histones that have multiple combinations of

modifications. Using proteins that recognize these modifications, the idea is to screen these proteins to determine which combinations of modifications these proteins will bind to [4]. The hope is to eventually understand exactly how expression works so that one day, numerous health problems might have a solution.

Prashant Angara ‘12 is undecided in his major

References

1. “Genetics & Genomics Timeline,” 2004, <http://www.genomenewsnetwork.org/resources/timeline/timeline_ overview.php>. 2. B.D. Strahl, C.D. Allis. Nature, 2000, 403, 41-45. 3. Interview with Mike Parra, Ph.D, 10/1/09. 4. Interview with Brian Strahl, Ph.D, 10/6/09. 5. W. S. Klug in Concepts of Genetics, (Prentice-Hall, 2005).

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Tag, you’re it!

Discovering a new receptor to analyze gene repression Garrick Talmage, Staff Writer

NA is the building block of life. Sequences of nucleotides encode the genes that are expressed as proteins in cells. To fit all of an organism’s DNA into the cell’s nucleus, proteins called histones wind DNA into a condensed figure [1]. These small units called nucleosomes, as shown in Figure 1, allow DNA to be highly compacted [1]. It turns out that histones actually have another important function. Chemical alterations of histone proteins can lead to the deactivation of the gene it surrounds. Dr. Marcey Waters, from UNC’s Chemistry Department, is inFigure 1. A tightly compacted terested in the methylation of the amino nucleosome [2]. acid lysine in the tail of histone. At the end of lysine is nitrogen bonded to three hydrogens and in methylation, each of the three hydrogens attached to the nitrogen can be replaced by a –CH3 (methyl) group (see Figure 2) [2]. Figure 2. Methylation of lysine.

When three methyl groups are substituted in the lysine in the tail of histone, the methyl groups interact with a group of proteins called the HP1 chromodomain. The HP1 chromodomain is part of a family of

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proteins that interact with histones only if the amino acid lysine has been methylated two or three times [3]. The faces of the benzene rings in the HP1 chromodomain, as shown in Figure 3, are attracted to the methyl groups on lysine. This is because the benzene ring’s faces have a partial negative charge, while the methyl groups have a partial positive charge. Since opposite charges are attracted to each other, the HP1 chromodomain attaches itself to the histone [2]. When this occurs, the HP1 chromodomain can repress the expression of the gene surrounded by the histone [3].

Figure 3. Interaction of HP1 chromodomain with a trimethylated lysine [2].

Dr. Waters’s research group aimed to synthesize a molecule that would bind to a methylated lysine in the histone tail, just like the HP1 chromodomain does. If the molecule were labeled by a fluorescent tag, it would allow scientists to identify locations of histone methylations on a chromosome. The problem was making a chemical receptor that could easily be made but would have the important characteristics of the HP1 chromodomain, allowing it to bind to the methylated lysine. The answer—surprisingly enough—was a phenomenon taught every semester in any introductory chemistry class: Le Chatelier’s principle. Dr. Waters saw that she could use Le Chatelier’s ideas to her advantage to synthesize the molecule she wanted, using a new technique called Dynamic Combinatorial Chemistry (DCC).

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Figure 4. Schematic of Dynamic Combinatorial Chemistry. A) A mixture of monomers. B) Dynamic Combinatorial Library. C) Desired receptor bound to the trimethylated lysine template [2].

Le Chatelier’s principle states that when a chemical system is at equilibrium, the system will counterbalance any change that is made to it [4]. For example, if the concentration of a reactant is decreased, then the equilibrium will shift towards the reactants to try and counterbalance the change. How could this relate to DNA, methylation, histone proteins, and HP1 chromodomains? In order to synthesize the receptor that would interact with methylated histone tails, Dr. Waters put Le Chatelier’s principle to work. She made various mixtures of chemical compounds, called monomers (Figure 4A), each with several important characteristics. Many of the compounds in the mixture had at least one benzene ring that could interact with a methylated lysine. Second, all of the chemicals had two –SH (thiol) groups attached to the ring. In equilibrium conditions, the thiol group from one molecule could bind to the thiol group from another molecule, allowing the monomers to combine with each other to form receptors with the methylated lysine, as shown in Figure 4B. Because the receptors were in equilibrium with one another, the pieces of each could break apart and recombine with other pieces to form another receptor [2]. All the possible combinations of connected monomers formed a collection of receptors called the Dynamic Combinatorial Library (DCL). Next, the DCL was exposed to the methylated lysine, the template. Interaction between a receptor and the methylated lysine resulted in an increase in the concentration of the bound receptor along with a decrease in the concentration of the unbound receptor that we want. Sound familiar? According to Le Chatelier’s principle, the equilibrium system then counterbalanced this effect by taking apart pieces of unbound, undesired receptors and using them to

make the unbound, desired receptor, which could then bind to the template. This process was repeated, over and over again [2]. The final concentration of the desired receptor then was much higher than it was before the reaction took place. By comparing the contents of the DCL before and after methylated lysine was inserted, Dr. Waters was able to find a receptor that would bind to methylated lysine [2]. The most exciting part about the resulting receptor was that it did not bind to unmethylated lysine, meaning that it could be used as a tag for histone methylation [2]. Since histones that are methylated cause gene deactivation, it could eventually be used to identify where histones are methylated in a chromosome. Such a receptor could be very useful in areas such as cancer research, as it can be used to determine which genes have been turned on or off in cancerous cells compared to normal cells [2]. This is a very promising area of cancer research and hopefully Dr. Waters and Le Chatelier can contribute to it in a unique way.

Garrick Talmage ‘12 is a Chemistry major with a Math minor

References

1. A. Griffiths, et al., in Introduction to Genetic Analysis (W. H. Freeman, 2007). 2. Interview with Marcey Waters, Ph.D. 9/28/09. 3. S. D. Taverna, et al., Nat. Struct. Mol. Biol. 2007, 14, 10251040. 4. S. Zumdahl, in Chemical Principles (Brooks Cole, 2007).

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Carolina Scientific

Not So Simple Symplekin:

Analyzing the Role of Symplekin in Histone Pre-mRNA Processing

Michelle Lin, Staff Writer

ue to the crucial involvement of histones in cell proliferation and animal development through DNA packaging and regulating gene expression, histone biosynthesis is of great interest. Of particular interest is the expression of histone messenger RNA (mRNA), which is intimately coupled to DNA synthesis [1]. In general, mRNAs are essential molecules involved in the translation of a genetic message (DNA) into a protein. These mRNAs are synthesized through transcription from genomic DNA [2]. During the process of transcription, one strand of double stranded DNA is used as a template for constructing a complementary RNA sequence [3]. To become “mature” mRNAs, these newly made or “pre” mRNAs must undergo processing. Typically, the non-coding sequences of DNA, introns, are removed and the 5’end and 3’ end of the mRNA is capped for recognition and protection from enzymatic digestion (see Figure 1) [2].

Figure 1. mRNA processing after synthesis from DNA [10].

Many aspects of histone mRNA set it apart from general mRNA. As mentioned earlier, the expression of histone mRNA is highly cell-cycle dependent. When cells enter the DNA synthesis phase of the cell cycle, histone mRNA levels rise [1]. At this point in the cell cycle, histones are needed to package newly synthesized DNA into chromatin. By the end of the synthesis phase, histones are no longer needed, so histone mRNAs are rapidly degraded and their levels decline. Furthermore, unlike regular pre-mRNA, histone pre-mRNA lacks introns and a cap is not added to the 3’ end of the mRNA, ending in a highly conserved 3’ stem loop sequence instead. This stem loop sequence is necessary for 3’ end processing and stability. As a result the synthesis of mature histone mRNAs requires just one unique processing reaction: single

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cleavage of the 3’ end of the mRNA, which in turn forms the stem loop sequence [4]. Seems simple, right? Wrong! This unique processing reaction actually involves many proteinprotein interactions and several factors that are housed in the histone locus body, a subnuclear organelle that also contains re- Figure 2. Many proteins are petitive histone gene involved in the cleavage of the clusters [5]. 3’ end of the pre-mRNA. Histone-specific pre-mRNA processing factors such as the stem loop binding protein (SLBP) and the histone downstream element bind to the pre-mRNA at specific locations to position the pre-mRNA in preparation for the cleavage of the 3’ end of the pre-mRNA. A core cleavage complex consisting of symplekin and other proteins called CPSF73 and CPSF100 is recruited to cleave the 3’ end of the pre-mRNA (see Figure 2) [6]. Due to the interdependent nature of these protein interactions, scientists are presented with great difficulty when trying to isolate and identify the function of each individual protein. The Duronio Lab at UNC-CH focuses on how gene expression is controlled during the cell cycle, especially at the transition from the gap phase into the synthesis phase. Because histone mRNA levels increase dramatically during this transition, many members of the Duronio Lab and the Marzluff Lab are curious about the biosynthesis of histones, including all the proteins involved in this process. One protein of interest in the Duronio lab is symplekin and I am working with graduate student Deirdre Tatomer to study its role in histone pre-mRNA processing. As stated earlier, symplekin is a part of the cleavage complex during pre-mRNA processing. This protein is believed to function as a scaffolding protein, bringing together various proteins to position them in the larger processing complex [3]. To better understand the role of symplekin in histone pre-mRNA

Carolina Scientific processing, Tatomer decided to examine where symplekin is localized during development. Specifically, she analyzed tissues in varying developmental stages to see if there were any differences in symplekin’s location. Tatomer discovered that in within fruit fly (Drosophila melanogaster) embryos, symplekin localizes to the nucleus and is detected in the histone locus body of cells. Because mRNAs are transcribed and processed in the nucleus of cells, the presence of symplekin in the nucleus is logical. Furthermore, since embryos are in the process of development and cells are still proliferating, symplekin may be localized in the histone locus body to help facilitate the interaction between the histone processing factors for histone synthesis. In Drosophila melanogaster ovarian tissue, Tatomer discovered that symplekin still localizes to the nucleus of cells. However instead of being detected in the histone locus body (as in embryonic tissue), symplekin was seen at tight junctions, barriers between cells that prevent molecules from diffusing between cells. Proliferation is no longer occurring in fully developed and differentiated ovarian tissue and as a result, symplekin may be localized at the tight junctions instead because the histone processing factors located in the histone locus body are no longer needed. These results suggest that the localization of symplekin varies based on the stage in development and differentiation of a tissue [5]. To advance the studies of Tatomer, I examined the localization of symplekin in Drosophila melanogaster larval imaginal eye discs. Imaginal discs, in general, are clusters of cells that proliferate during larval development to form folded, single layer epithelial sacs. From these imaginal discs, specialized adult structures arise that become part of the fruit fly’s hard, external skeleton [7]. For example, imaginal eye discs eventually become the eyes of the fruit fly (see Figure 3). Because eye discs contain differentiated cells on one half and proliferating cells on the other half, by examining eye discs, we can compare and contrast the localization of symplekin in proliferating and differentiated cells and at specific points in the cell cycle all at the same time. Figure 3. In Drosophila These two different melanogaster, each larval types of cells are sepaimaginal disc gives rise to a rated by a morphogeseparate adult structure [10]. netic furrow, an inden-

tion in the epithelium, where there is a wave of cells participating in the cell cycle [8]. By fixing, permeabalizing, and staining these eye discs with different antibody markers, we can track the location of symplekin. Variation in the degree of success in removing a thin membrane from each eye disc to facilitate the even distribution of antibodies through the tissue caused unwanted antibody accumulation on the surfaces of the eye discs and therefore unpredictable staining. This lack of consistency in results in these experiments fail to convincingly support Tatomer’s results that show that symplekin is located in the nucleus and histone locus bodies of proliferating, developing cells and while in fully differentiated cells, it is located in the nucleus and tight junctions. Future directions include continuing to optimize staining procedures as well as attempting to determine symplekin localization in the morphogenetic furrow in cells at specific points in the cell cycle. Although progress is indeed being made towards understanding the role of symplekin in histone premRNA processing, there is still much to be discovered and many other aspects of histone biosynthesis that are not fully understood. The drive to develop a comprehensive understanding of histone biosynthesis is fueled by the increasing understanding of the structural and functional properties of the eukaryotic genome and secured by the essential roles of histones [9].

Michelle Lin ‘12 is a Biology major with a double minor in Chemistry and Chinese

References

1. L.S. Hnilica, in Histones and Other Basic Nuclear Proteins (CRC Press Inc., 1989). 2. A. Liljas, in Structural Aspects of Protein Synthesis (World Scientific Publishing Company, 2004). 3. S. Kennedy. UNC Dissertation. 2009, 1-7. 4. B. Marzluff, et al. Curr. Opin. Cell Biol. 2002, 6, 692-629. 5. Interview with Deirdre Tatomer, Dept. of Biology. 9/28/09. 6. K.D. Sullivan, et al. Mol. Cell. 2009, 3, 322-332. 7. G. Morata. Nat. Rev. Mol. Cell Biol. 2001, 2, 89-97. 8. J. Curtiss, et al. Development. 2000, 127, 1325-1336. 9. G.S. Stein, in Histone Genes: Structure, Organization, and Regulation (John Wiley & Sons, 1984). 10. D.O. Morgan, in The Cell Cycle: Principles of Control (New Science Press, Ltd., 2007).

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Carolina Scientific

A Superbubble Bath Apurva Oza, Staff Writer

f you have ever been that curious boy or girl looking up at the night sky, on a mid-summers night, or any clear night really, you have appreciated the limitless tranquility emanating from each twinkling star the dark ocean of the sky brings. Upon seeing these stars, we are immersed in the complete awe of the cosmos; we feel at home in a safe haven—sort of like a bubble of serenity. If we dare venture out of this bubble, what will we find? If we choose one particular “star” in the sky, “zoom in” so we are directly overseeing its world, will we find the same placidity? Absolutely not. Once we leave the confines of planet Earth, and our Milky Way Galaxy, our bubble of comfort also vanishes. That particular “star” is actually

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a combination of billions of stars, representing a galaxy. Simply put, this galactic world is Chaos. Calamity. Destruction. Marred by explosion after explosion. This is the world astrophysicist Gerald Cecil lives in—the world of Active Galactic Nuclei (AGN—A highly luminous galaxy with a supermassive black hole at the center [1]). When astronomers and astrophysicists like Dr.Cecil ”zoom in” on these galactic environments of turmoil, they are not only zooming in on a star, but zooming into the past as well. Astronomers are seeing light that is billions of years old, and in this era of time we are at a peak of AGN activity [2]. This was a time of complete unrest—the early Universe was more condensed

and closer together, with galaxies merging & colliding, star deaths triggering supernova explosions, Gamma-ray bursts exploding, and Quasars (subsets of AGNs) ejecting highly energetic jets [1]. All of these phenomena comprise the study of “galaxy formation and evolution,” they are all manifestations of our Universe’s past, and have remarkably molded the Milky Way’s environment. “In order to understand how this whole system works, you need to understand these pieces and how they fit into the whole scheme,” Dr.Cecil comments. Dr. Cecil’s piece of the puzzle concerns another chaotic explosion—Superbubbles; They are giant bubbles of extremely hot gas (more than millions of degrees Kelvin), that explode from the centers of AGNs like shock waves, and span thousands of light years. Cecil uses a variety of instruments Figure 1. A and techniques to explore these composite image Superbubbles. He has used the of Superbubble NASA Spacecraft, Chandra X-ray NGC 3079 taken by Hubble Space Telescope, and the Hubble space Telescope (HST). In telescope to image these bubbles the first two images so that he can later analyze them the center nuclear with his team using spectroscopy region is magnified, and other techniques. “The interwith the plus sign esting thing about these bubbles indicating the active is,” Dr.Cecil says, “when you galactic nucleus think of an explosion you think itself. of parts flying everywhere like a bad science fiction movie, but this thing has a structure to it, you can

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Figure 2. Here is an image Dr.Cecil and his team took with the Hubble space telescope, of galaxy NGC 3079. As you can see the bubble is protruding directly from the center of the galaxy, and in the top right of the image you can see the structure and arms of the bubble [3].

see there are almost arms sticking up out of the disk, there’s a history here, stuff has been lifted up into the air, so it’s probably not just something like a point explosion, but something that’s acting more continuously, more like a wind. This [stuff ] pops out and then a wind blows on it to lift it up.” Today Dr.Cecil is mainly spending his time on spectroscopy and Instrumentation, building instruments so that he can better detect these bubbles with greater precision. Cecil explains what keeps him motivated everyday: “Largely, that if you do the experiment right, with modern facilities, you see things that people have never

Figure 3. Image of a nearby AGN (M82) [3].

seen before, you see them clearer, and suddenly you see something that explains a mystery that’s been lying around for decades. Oh there it is! That’s why it looks that way! And Hubble [space telescope] did that because it just got sharper images. Techniques such as spectroscopy, give additional physical insight. Pictures are a prelude to the spectroscopy, in which we find our fascinating patterns and regions.” There are two theories on the main cause of these superbubbles. One less prominent theory is “stubby jets.” These are jets that don’t go too far from the AGNs, and they interact with gas around the galaxy that produce shock waves that expand the hot gas outwards creating a bubble-like cocoon around it, creating bubbles, Cecil explains. The leading theory suggests that superbubbles are triggered by hundreds of supernova explosions, “ which are highly uncommon for a typical galaxy, but certain galaxies enter these ‘starburst phases,’ where stars explode in sequences or coordinated explosions, and each explosion produces a little bubble, and all the little bubbles collectively form

a superbubble.” And thus, it is these kinds of patterns and clues that Astronomers pick up on, that characterizes our current understanding of the Universe. It is these discoveries that let us know what is truly going on beyond our misleading celestial sanctuary. Although our sky brings a great complacency, one must know that peering deep into the cosmos, brings a battleground of cataclysm. A bath of chaos.

Apurva Oza ‘12 is a Physics major

References

1. R. Antonucci, et al. Annu. Rev. Astron. Astrophys., 1993, 31, 473-521. 2. I. Robson, in Active Galactic Nuclei. (New York: Praxis Publishing, 1996.) 3. G. Cecil. Sci. Am., 2007, 274, 86 - 91. 4. G. Cecil, et. al. Astrophys. J. 2001, 555, 338-355.

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Genetic Divergence and Reinforcement of Species Differences Elizabeth Bergen, Staff Writer

hen closely related species come into contact with one another, whether due to natural occurrences or human disturbance, they may have the opportunity to hybridize, or produce offspring with one parent from each species. For example, when a horse and a donkey mate, they produce a hybrid called a mule. While mules are sturdy, useful animals, they are sterile and therefore unable to pass on the genes they have inherited from their parents. In evolutionary terms, the hybrid mule has lower fitness than a pure horse or donkey. In the farmyard, a farmer chooses to breed the horse and donkey together. In the wild, however, the likelihood of hybridization depends on individuals’ preferences, which make them more or less inclined to mate with members of other species by mistake. In an evolutionary process called reinforcement, closely related species in proximity to each other

Figure 1. Speciation maintained through reinforcement. Producing hybrids, which have lower fitness, reduces the parents’ long-term fitness. Natural selection favors parents that choose not to hybridize [1].

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remain distinct because hybrids of the two species have reduced fitness. The reproductive fitnesses of parents are thus dependent on their preferences for mating with conspecifics, or members of the same species [1]. When the most fit individuals in the

Dr. Maria Servedio Associate Professor of Biology

population prefer to mate with conspecifics, the two species are unlikely to merge into a single species composed entirely of hybrids. Reinforcement is an important theoretical requirement for several theories of species divergence, but its role in the process of speciation, or the formation and maintenance of species distinctions, is not well understood. Dr. Maria Servedio and the members of her lab model the evolutionary behavior of a variety of populations with sets of complex and interrelated mathematical equations. One of her primary goals is to build models that explore how different biological factors affect the feasibility of reinforcement as an explanation for the persistent separation of species in physical proximity to each other. Mathematical models constructed by Dr. Servedio have demonstrated that reinforcement can operate under a broad range of biological conditions [1].

Carolina Scientific Bird song Learning Affects Speciation Rate The order Passeriformes, or songbirds, contains many distinct species that are closely related to each other. The high number of species within this order suggests that speciation has probably occurred at a rapid pace among the songbirds. The cultural transmission of bird song, by which an individual announces his species to potential mates, may have contributed to this increased rate of speciation. Dr. Servedio compared two models of songbird populations to determine whether certain types of species divergence occurs more readily in species where song is learned from other individuals. In one model, an individual’s song was determined solely by his genetic makeup. In the other, an individual’s genotype determined how he learned different songs from other members of the population. According to her models, song learning reduced selection against unusual genotypes. Therefore, greater variation persisted in populations with cultural song transmission, which accelerated the rate of divergence [2]. Models of speciation within populations that are in geographical contact typically assign very simple rules to govern mate choice. However, mate choice may be governed by a variety of genetic and developmental factors. Sexual imprinting is a process by which an individual’s mate choice preferences are determined in part by their exposure to other individuals. Dr. Servedio has examined how sexually imprinting on different targets affects the likelihood of speciation in birds. Among other findings, she

Figure 3. Simulations of four mating modes. The x-axes represent time (0-1500 years) and the y-axes represent the value of the phenotype. The gray-scale represents how many individuals had that phenotype at that time (black, all individuals had that phenotype; white, no individuals had that phenotype) [3].

discovered that, when females imprint on their mothers, speciation occurs more easily than when females imprint on their fathers or other individuals in the population [3].

Elizabeth Bergen ’10 is a Biology major Figure 2. When individuals vary in their ability to recognize the notmal songs sung by conspecifics, aberrant recognizers can diverge from the population’s norms and become fixed around a different norm [2].

References

1. M. Servedio. “Speciation and Reinforcement,” 2009, <http://www.bio.unc.edu/Faculty/Servedio/Lab/Research. html>. 2. R.F. Lachlan, et al. Evolution 2004, 58, 2049-2063. 3. M.N. Verzijden. Evolution 2005, 59, 2097-2108.

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Carolina Scientific

It’s Gonna be a Long Night... Ameer Ghodke, Staff Writer

t’s 11 pm and you have an organic chemistry midterm tomorrow. With an obvious all-nighter ahead, an energy drink seems inevitable. When that bitter taste runs down your throat, and your eyes suddenly widen, what exactly is going inside your body? Is 5000% your daily intake of vitamins B6 and B3 okay? Why does Amp© have L-theanine in it and does it really increase the number of alpha waves in your brain?

greater role in the “crash” after consumption. Another ingredient infamous in most energy drinks are the B vitamins, specifically B6 (pyridoxine) and B3 (niacin). Vitamin B6 is a water-soluble vitamin that is essential to good health: in moderate doses, it promotes protein metabolism, red blood cell metabolism, and participates in other bodily functions [3]. However, a can of Red Bull has 250% the recommended daily value of vitamin B6. According to the Food and Nutrition Board of the Institute of Medicine, an excess of vitamin B6 can cause nerve damage to arms and legs [3]. Vitamin B3 is also a water-soluble vitamin that helps the body make various hormones in the adrenal glands and other parts of the body. It also effectively improves circulation and reduces cholesterol levels in the blood. Vitamin B3 has a recommended maximum intake level of 35 milFigure 1. Structure of Taurine. ligrams daily [4]. One can of Monster energy conEnergy drinks seem to be the key to surviving tains close to 60 milligrams of niacin. High doses of late nights in school and even the early mornings that vitamin B3 can cause a burning sensation in the face follow. But what exactly are we consuming in the or chest, which also causes “flushed” skin [5]. Exprocess? One of the most common ingredients in en- cess levels of this vitamin over a long period of time ergy drinks is taurine. Taurine, or 2-aminoethanesul- can cause liver damage and stomach ulcers as well. fonic acid, is a nonessential amino acid that is very Thus, these vitamins should be ingested in moderaabundant in the human brain. The commercial tau- tion. More than one energy drink per day and several rine found in most energy drinks, such as Red Bull, energy drinks per week can be a precursor to these is a synthetically manufactured chemical. Research- serious problems. ers at Cornell have discovered that in the part of the L-theanine is another ingredient now found brain known to control sleep and wakefulness (the uniquely in AMP© energy drinks which claim to sigthalamus), specific receptors called GABA (gammaaminobutyric acid) receptors may be strongly acti- a) b) vated by taurine [1]. These receptors are normally activated by a neurotransmitter called GABA, a molecule that is known to have inhibitory effects on the brain [2]. Little is known about taurine’s exact effects on the brain but they are said to be similar to the GABA effects, which is mostly neurological development and cell to cell connections. However, the Cornell researchers found that taurine seems to have Figure 2. a) Stucture of Vitamin B6. more of a sedative effect on the brain and may play a b) Structure of Vitamin B3.

Fall 2009, Volume II Issue I

Carolina Scientific

Figure 3. Structure of L-theanine.

nificantly increase concentration and reduce stress. As an amino acid derivative most commonly found in tea, L-theanine has been advertised as a compound that increases alpha wave activity in the brain. The brain produces different frequencies for different levels of attention and alpha waves are responsible for the relaxed mental state [6]. There has not been

much research done as of yet on the health risks involved with L-theanine; however, studies have indeed shown that L-theanine is related to increased alpha brain wave activity. This finding was concluded in a study in which 13 people received 250 milligrams of L-theanine or a placebo over a period of time and then performed spatial attention tasks [7]. While studies like these seem to indicate the benefits of L-theanine, significant research has not been completed whether there is a direct relationship between the effects of caffeine and L-theanine on each other together. Thus, the practical effects of L-theanine are not well known. Overall, energy drinks can be very risky to consume in excessive quantities. These three chemicals are consistently found in many of the leading commercial energy drinks today. With the taurine levels, B vitamins, and other ingredients such as L-theanine, it may be fine to drink one energy drink for a busy night; however, we should always drink in moderation.

Ameer Ghodke ‘12 is a Chemistry major

References

Figure 4. Comparison of nutrional facts for different popular brands of energy drinks

1. J. Fan, et. al. J. Neurosci. 2008, 28, 106-115. 2. R. Swenson, in Review of Clinical and Functional Neuroscience (Dartmouth Medical School, 2006). 3. NIH. “Dietary Supplement Fact Sheet, 2007, <http://ods. od.nih.gov/factsheets/vitaminb6.asp>. 4. W. Snow. “Vitamins: Recommended Intake Levels,” 2003, <http://www.supplementquality.com/news/multi_vitamin_ chart.html >. 5. S. Ehrlich. “Vitamin B3: Niacin,” 2007, <http://www.umm. edu/altmed/articles/vitamin-b3-000335.htm>. 6. B. Gottfried. “Brain Activity,” 2002, <http://www.ldrc.ca/ contents/view_article/219/>. 7. M. Gomez-Ramirez, et. al. Brain Topogr. 2009, 22, 44-51.

Fall 2009, Volume II Issue I

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Yeast, A Human Stand In Mary Gallo, Staff Writer

r. Kerry Bloom’s office is tucked away into the back of a bustling laboratory in Fordham Hall. The ordered chaos of his office suited him well as he sat unassumingly waiting for the barrage of questioning to begin. His research is focused on chromosome segregation, which involves cell replication and division. In mitosis identical copies of the chromosomes segregate and produce two identical cells. In meiosis, the process by which sperms and eggs are produced, the chroProfessor Kerry S. Bloom mosomes do not divide identically and there is a random arrangement and distribution of the chromosomes to the gametes (sex cells such as sperm and egg). Dr. Bloom is interested in the kinetochores, tiny motors on the centromere of the chromosomes that are integral to chromosome segregation. He explained to me how the process took place using a Chinese finger trap; he illustrated that there was a coupling device, similar to a Chinese finger trap, between the chromosomes. The spindle attaches to the kinetochore and when the right tension is generated the chromosomes segregate. The reason that this process is so compelling is that an error in chromosome segregation can give rise to cancer cells, birth defects and a myriad of

Figure 1. Humans have 23 pairs of chromosomes.

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Figure 2. Schematic of mitosis, the process in which a cell divides to produce two identical cells.

other disorders. There are 46 chromosomes in a human cell and if even a single chromosome is improperly segregated that equates to an error in 1/46 of the genetic code; a fraction that is significant enough to equate to a fatal error. As Dr. Bloom explained, “Everything in moderation – life needs to be balanced” and when that balance is disrupted by a malfunction in chromosome segregation Dr. Bloom is watching to understand how we can restore the balance [1]. Dr. Bloom works with yeast, because he can easily examine their mitotic cycle. He draws parallels between yeast and human cells because of the strikingly similarities in their comparative cell cycles. Yeast and humans have the same spindle apparatus and their chromosomes carry out the same genetic function. He discussed how yeast proves the theory of evolution because yeast is evidence of how the process of chromosome segregation has been conserved from the earliest eukaryotic organisms. These organisms were naturally selected because they could successfully and efficiently transmit genetic information. His own research involves constructing DNA sequences and adding that DNA to yeast cells to alter them, giving the cell a function it did not previously have of stripping it off a function it did already have, ie. an inability to produce leucine, an amino acid. By observing how the mitotic cycles proceed and the role of the kinetochores he can be better understand how these processes fail and how to correct errors that arise. The ultimate goal would be to

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Figure 3. Left: A cell that is dividing properly (the chromosomes are blue and the spindle is red) with all chromosomes separated correctly. Right: A cell in which there is an error--a pair of chromosomes (seen in blue) have not segregated properly and remain in the middle.

Bloom, while explaining that the universe is moving towards chaos, and entropy is always increasing, also pointed out that the cell remains surprisingly organized while benefiting from the diversity that the increasing entropy generates. Dr. Bloom’ s research of chromosome segregation is bringing together different branches of science to work towards one goal: understanding the intricacies of chromosome segregation. Biologists, chemists and physicists are each adding a different scope of knowledge and experience as we begin to appreciate the significance of the fact that genes are both biological entities, complex chemicals and entropic springs.

cure diseases at the level of the gene by identifying the mutation that gives rise to the error and inserting a gene sequence that corrects the error. Right now the field of genetics is excitingly fast paced--in the last fifty years Watson and Crick have proposed the theory of double helix DNA molecules Mary Gallo ‘10 is an English major and the entire human genome has been sequenced; References as Dr. Bloom said “we have all the parts for creating a cell” but we can’t make a cell quite yet. Dr. 1. Interview with Kerry S. Bloom, Ph.D. 9/23/09.

You are young and invincible! Just don’t forget to put on your lab coat, goggles and gloves before your next experiment. A precaution here, a precaution there, first thing you know, safety becomes a habit. Some call it the culture of safety; we just call it taking care of yourself and others in your lab. If you have a question about lab safety, call or email us at 962-5507, or labsafety@ehs.unc.edu.

We are EHS: Your lab safety resource

Fall 2009, Volume II Issue I

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Undergraduate Research Spotlight:

SUMMER UNDERGRADUATE RESEARCH FELLOWSHIP The Summer Undergraduate Research Fellowship (SURF) program was created by the Office for Undergraduate Research (OUR) in 2001, when we made 11 awards. The program has grown steadily since then (in 2009, we made 75 awards). The program has raised undergraduate awareness of opportunities to work with faculty in all disciplines, contribute to the University’s research mission, and do things that no one has ever done before. These experiences allow students to develop new skills, meet others with similar interests, gain confidence, define their own styles, and make informed decisions about future career paths. 2010 SURF Information meeting: Jan. 26, 2010, 5:30-7:00pm FedEx Global Education Center, Rm 1005 Hear from successful applicants, ask questions about the application and selection process, and learn more about SURF Peer Advisors who can give you valuable feedback on your proposal before you submit it! Eligibility: All currently enrolled UNC-Chapel Hill undergraduate students in good academic standing who will graduate after November 2010 and who wish to engage in undergraduate research, scholarship or performance for at least 9 weeks, with a minimum 20 hours/week, between May 10, 2010 and August 22, 2010 are eligible to apply. The projects must be carried out under the supervision of a UNC-Chapel Hill faculty research advisor, and additional collaboration with a postdoctoral fellow or graduate student mentor is encouraged. PLEASE NOTE: Each student may submit only ONE SURF application/year. Students who have received SURF awards in previous years are not eligible to apply for additional SURF awards. Students may not accept both a SURF award and a Burch Fellowship award for the same summer.

Name: Amanda Sullivan, Class of 2011 Major: Physics and Math 1. Please briefly describe your SURF project and how did you come up with it? For my SURF project, I worked with optical coherence tomography (OCT), which is a technique that can be used to obtain two- or three-dimensional images of biological tissue. The lab I was working in already had several breast tissue samples from mastectomy patients. I imaged some of these with the OCT system, then analyzed the images for interesting features. In addition, the actual tissue samples were processed and stained by another lab, so I could compare my images to tissue slides. My goal for this part was to find the correlations between the two, so I would know how the different breast tumors and lesions appeared in the OCT images. Dr. Oldenburg proposed the idea to me when I first started working in her lab, and I thought it sounded very interesting, so I agreed to do it. 2. Overall, how was your research experience and what did you gain from this summer? On the whole, my experience this summer was very enjoyable. At first, I was nervous because I thought I would mess something up or not know how to do it, but the longer I worked in the lab, the more comfortable I became. Dr. Oldenburg and Raghav, my graduate student mentor, were always very helpful and took the time to explain what was going on when I was having trouble. I quickly learned that research is more effective as a group process, rather than an individual one. The thing I enjoyed most about the summer, though, was being part of something meaningful. The work itself was not always fun, and could sometimes be very frustrating, but knowing that it could someday make a difference in somebody’s life was enough to keep me going. As a result, I feel like I accomplished a lot over the summer, and I really enjoyed myself as well. 3. Are you still involved in research? If not, why and do you plan to do so in the future? I am still involved in research in the same lab I worked in over the summer. I plan to continue working there as long as possible, hopefully through my senior year.

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Carolina Scientific Name: Kyle Trettin, Class of 2011 Major: Chemistry (Biochemistry track) 1. Please briefly describe your SURF project and how did you come up with it? My SURF project focused primarily on characterizing the role and function of a specific protein, Kes1. Kes1 had previously been identified as a negative regulator of the secretory pathway in cells. The secretory pathway is necessary for cell viability. While it had been previously shown that Kes1 plays a regulatory role, it remained unclear as to how it carries out this function as well as what regulates its activity. My research focused on elucidating these remaining points. I started working on this project shortly after joining a research laboratory run by Vytas Bankaitis in the Fall semester of my sophomore year. I worked closely with a post doctoral fellow, Carl Mousley, whose previous and continued work provided the foundation for my project. 2. Overall, how was your research experience and what did you gain from this summer? The SURF allowed me to gain a more realistic perspective of what its like to be a fulltime researcher spending at least 40 hours a week in the lab, something that is nearly impossible to do as a fulltime student during the academic year. It’s easy to think you’re interested in a career in research when you’re only spending a few hours a day in the lab, which was my case during the academic year. My overall research experience was invaluable. I feel the concepts and skills I learned over the summer will serve me well in future studies and endeavors. 3. Are you still involved in research? If not, why and do you plan to do so in the future? I am currently still working in the Bankaitis lab and plan to continue working there until I graduate. Based on my experiences thus far, I plan to attend graduate school in biochemistry and pursue academic research. Name: Cameron Isaacs, Class of 2010 Major: Biology with a Chemistry minor 1. Please briefly describe your SURF project and how did you come up with it? The primary focus of my SURF project was to better identify and characterize the function of SAUR proteins in Arabidopsis thaliana, and to integrate these results with existing knowledge of auxin signaling and response pathways. Small Auxin Up RNAs (SAURs) are a family of primary auxin-responsive genes of unknown biochemical and developmental function. My SURF project was an extension of my previous work with these proteins under the guidance of Dr. Jason W. Reed of the UNC Biology Department. Our preliminary research generated a myriad of possible research opportunities, but my primary interest was the characterization of SAUR-related phenotypes and the localization of SAUR proteins. After my initial proposition, I worked closely with Dr. Reed and other members of his laboratory to design and complete my project. 2. Overall, how was your research experience and what did you gain from this summer? Summer research at UNC is something that I recommend to any UNC undergraduate. Outside of the obvious benefits of invaluable undergraduate laboratory experience, the SURF program afforded me a concrete and obtainable objective for the summer. To research in the laboratory of such a distinguished plant biologist and to collaborate with such dedicated and intelligent post-doctoral researchers was truly rewarding. My experience expanded my understanding of plant biology and improved my analytical thought processes. The SURF program provides a unique opportunity for UNC undergraduates to contribute to one’s respective academic field. It is programs such as this that make UNC such an outstanding research environment. 3. Are you still involved in research? If not, why and do you plan to do so in the future? After completing my SURF project, I have since continued my research on SAURs in Dr. Jason Reed’s laboratory. I hope to complete and defend my Senior Honors Thesis on this topic next semester.

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Carolina Scientific Name: Beth Sams, Class of 2011 Major: Computer Science and Information Science double major, Math minor 1. Please briefly describe your SURF project and how did you come up with it? My first goal of the summer was to research the most effective ways for seniors to improve their balance. With the help of Dr. Shubert, a physical therapist with the School of Public Health and research scientist at the Institute of Aging, I explored different possibilities for balance interventions. I then selected the best candidate which would be implemented by modifying existing technology to build a low-cost solution. With Dr. Shubert’s guidance, I decided to use the Otago Exercise Program from New Zealand since it is already proven to significantly reduce fall rates among participants. I then investigated the different pre-existing commercial equipment to see if it could be used to track movement precisely enough. Dr. Bishop, a computer science professor, assisted me in understanding what capabilities the hardware would need. I worked with the Wii Balance Board and Wii Remote and found that both provided data precise enough for the project. Since it was smaller and less expensive, I decided to use the Wii Remote to track the user’s motions. Then, I began to put all the technology into a cohesive system. After much discussion with Dr. Bishop and Dr. Shubert, I created a web-based prototype where the user completes the exercises by following video segments with a Wii Remote strapped to him. This fall, the prototype will go into testing with different focus groups and research subjects. This information will allow me to improve both the health benefits and user experience of the system. I’m sure many details will have to be changed, but the finished product will be accessible, easy to understand, and provide major health benefits. I picked this topic after talking to Dr. Bishop about the upcoming summer. He had several ideas, and I was drawn to this one. 2. Overall, how was your research experience and what did you gain from this summer? I felt my research experience was a great one. I was able to learn a lot in many areas over the summer. I learned that research isn’t always a linear process. Everything takes much more time than originally planned, and many unexpected events occur. The SURF experience has opened up many more avenues that I gave any consideration to previously. I never play video games, but I enjoyed the subject of health gaming. 3. Are you still involved in research? If not, why and do you plan to do so in the future? I am currently still working on this project. I am moving the system to a web-based framework so seniors can access the exercises over the web and the physical therapists can see their patient’s results from their office.

NEED $$$ FOR A SUMMER IDEA? Other Summer Research Fellowships: 1. Taylor Research Fellowship DEADLINE: TBD All currently enrolled UNC-Chapel Hill Honors students in good academic standing who will graduate after November 2010 and wish to engage in undergraduate research or artistic projects for at least six (6) weeks between May 10, 2010 and August 22, 2010 are eligible to apply. Recipients will receive $4000 each. 2. Science and Math Achievement and Resourcefulness DEADLINE: February 26, 2010 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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A Special Thanks To Our: Production Staff

Staff Writers Amy Abramowitz Prashant Angara Ranjan Banerjee Elizabeth Bergen Abby Bouchon Vahini Chundi Keith Funkhouser Mary Gallo Ameer Ghodke Mary La

Michelle Lin Jesse Lomas Kevin Macon Frank Mu Apurva Oza Rebecca Searles Rohan Shah Garrick Talmage Amanda Traud

Elizabeth Bergen Natalia Davila Lenny Evans Carolyn Johnson Ann Liu Frank Mu Rebecca Searles Rohan Shah Kristina Stanson

Production Staff (Left to Right): Frank Mu, Rohan Shah, Rebecca Searles, Kristina Stanson (Not shown): Carolyn Johnson and Elizabeth Bergen

Also, a very special thanks to Vice Chancellor Tony Waldrop, the College of Arts and Sciences, the Biology Department, the Chemistry Department, the Physics Department, and the Eshelman School of Pharmacy for their generous donations. 43

Fall 2009, Volume II Issue I

â&#x20AC;&#x153;Research is formalized curiosity. It is poking and prying with a purpose.â&#x20AC;? ~Zora Neale Hurston

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Fall 2009

Front Cover: We apply methods in Network Science to look at community structure in United Nations General Assembly. In this visualization we color the countries geographically, and place the three communities we find in the 1982 assembly using the Fructerman and Reingold algorithm. Credit: Kevin Macon and Amanda Traud

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