fall 2009 issue

sc1ent1ficcarolina Undergraduate Magazine UNC-Chapel Hill

Fall 2009 Volume II, Issue I

Carolina Scientific

Fall 2009, Volume II Issue I 2

For more information, please email us at:

carolina_scientific@unc.edu or visit us online at: http://studentorgs.unc.

edu/uncsci

From the EditorsTo our readers: 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

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.

~Ann Liu is a junior majoring in Biochemistry and

Business

~Lenny Evans is a junior majoring in Physics and Math

~Adele Ricciardi is a junior majoring in Biochemistry and

Biology

~Natalia Davila is a junior majoring

in Studio Art with a minor in Chemistry

Carolina Scientific

Fall 2009, Volume II Issue I

Contents

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The RESOLVE Survey: A Closer Look at the Physics of Galaxies Rohan ShahMolecular Discrimination of Lung Cancers Keith FunkhouserNetwork Science: The Science of Connections Kevin Macon and Amanda TraudCell Signaling Therapy - Hope for a Seemingly Hopeless Cancer Abby BouchonHelping to Break the Habit: Naltrexone and Alcohol Dependency Mary LaBPA: Promoting Aggressive Behavior in Young Girls Rebecca SearlesA Nervous Development: from Neural Tube to Nervous System Amy AbramowitzKeeping the Beat Ranjan BanerjeeA Scientific Callin’: Probing Deeper into Colon Cancer Frank MuReproductive Immunity: Toll-like Receptors in the Human Endometrium Vahini ChundiArsenic in Drinking Water? A Dietary Approach to Improving Arsenic-Induced Diabetes Jesse LomasThe Histone Code Hypothesis Prashant AngaraTag, You’re It! Discovering a New Receptor to Analyze Gene Repression Garrick TalmageNot So Simple Symplekin: Analyzing the Role of Symplekin in Histone Pre-mRNA Processing Michelle LinA Superbubble Bath Apurva OzaGenetic Divergence and Reinforcement of Species Differences Elizabeth BergenIt’s Gonna be a Long Night... Ameer GhodkeYeast, A Human Stand-In Mary GalloUndergraduate Research Spotlight: SURF Compiled by Ann LiuAcknowledgements

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Have 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 Spec-troscopy 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 un-known. An undergraduate, Xuan Liu, has been work-ing 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-res-olution pictures Flexible Image Transport System (FITS) images. FITS are photograph files designed specifically for scientific purposes such as photomet-ric 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 asso-ciated 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-

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 emis-sions, which help determine the physical and chemi-cal 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 em-ployed the use of Interactive Data Language (IDL) primarily used for image analysis and array process-ing. 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. Mathemati-cal algorithms used by IDL then create three-dimen-sional graphs with information regarding magnitude of intensity of light (see Figure 1). Different light in-tensities aid in both determining the composition of the body as well as its movement data. This is imper-ative 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 col-or shifts give the team the ability to determine the

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

Figure 1. 3-D model created using IDL.

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

Carolina Scientific

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 incli-nation and orientation of galaxies in space. Inclina-tion 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 li-brary of model galaxy velocity fields which allow an increasingly multilateral representation of how ac-tual 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 galax-ies. The difference between radial and rotational ve-locities 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 in-formation 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 mat-ter 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 in-ternal 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.

References1. Interview with Xuan Liu, 09/30/2009.Figure 4. Milky Way galaxy.

Figure 3. Radical velocity maps of a galaxy.

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

Carolina Scientific

Keith Funkhouser, Staff Writer

For Greg Tsongalis, a Patholo-gist at Dartmouth-Hitchcock

Medical Center, it was a routine case: a female smoker with a his-tory of head and neck carcinoma is screened and found to have a lung tumor. The microscopic appear-

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 carcino-gens could have caused two in-dependent 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, sur-gically removed, and the patient should have a high chance of sur-

vival. In the second case, the pa-tient would be judged to have high stage head/neck carcinoma, treat-ed 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., Pro-fessor and Director of Graduate Studies in the Department of Pa-thology 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 in-stability of cancers, he knew that a primary tumor could lose al-leles (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 lin-eage of such tumors [1]. Due to the fact that a metastasis can show allelic loss but not allel-ic 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 inde-pendently (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 pat-tern of 1-5 nucleotides is repeated in sequence. The polymerase chain reaction (PCR) process is

Molecular Discrimination of Lung Cancers

William B. Coleman, Ph.D., Professor and Director of Graduate

Studies in the Department of Pathology and Laboratory Medicine

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

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used to amplify these polymor-phic 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 fo-rensic testing. STR alleles, which are lost in the tumor (loss of het-erozygosity, 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 prima-ries (Figure 3) [1]. When tumorigenesis occurs, there are certain genetic aberra-tions that are inherent in the neo-plastic clone, whether they are DNA breaks, rearrangements, in-sertions, deletions, or point muta-tions. Because these can result in LOH, if Tumor A metastasizes to Tumor B, there will be a trace-able 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 me-tastasis of Tumor A [2]. In con-trast, if any alleles are present in B that are not present in A (discor-dant 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. Distinguish-ing multiple independent primary cancers from metastatic cancers has a marked impact on tumor staging, the most important deter-minant of prognosis (survival). In addition, the study has potential to be applied to other forms of re-current 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 trans-lational medicine, which has been described as “bench to bedside.” In other words, the goal of trans-lational medicine is to develop scientific insights, which can then be used to systematically improve disease diagnosis and manage-ment. Dr. Coleman’s findings will ultimately improve patient care significantly for those with mor-phologically similar carcinomas of the head/neck and lung.

References1. Interview with William B. Coleman, Ph.D. 9/23/09.2. R.R. Mercer, et al. Exp. Mol. Pathol. 2008, 86, 1-9.

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].

Keith Funkhouser ‘13 is undecided in his major

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.

Carolina Scientific

In the Mathematics Department here at UNC there is a group of many undergraduate students, two grad-

uate 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 foot-ball teams to congressional committees--his research shows how network science, the study of intercon-nected systems called networks, can be applied in al-most 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 nano-tubes. 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 Sci-ence, 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 illustra-tions 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 anal-ysis 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 con-nected 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 heu-ristics 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.

Network Science:The Science of Connections

Kevin Macon, Staff Writer & Amanda Traud, Guest Writer

Carolina Scientific

strength (or edge weight) for analysis. Then for each network definition, it becomes a task to explore dif-ferent null models.

Visualizing Networks To visualize these networks, we used a combina-tion 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 at-tractive 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 at-tractive forces only between the US and England. This algorithm moves the nodes, or countries in our case, around until the energy resulting from this sys-tem 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 weight-ing 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

with a length equal to that of the number of hops be-tween 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 [3-4]. This research group uses network science in many areas including: epidemiology, material science, po-litical science, social networks, sports, and informa-tion science. Having tools with widespread applica-tions, this growing field connects people with diverse research interests. The authors of this article and members of the re-search group would like to acknowledge and thank Dr. Peter J. Mucha and Dr. Mason A. Porter for their support as advisors in research projects in network science with funding by, SURF, AGEP, the associate professor support program in the college of arts and sciences, and an NSF grant DMS-0645369.

Figure 2: UN Member Countries in 2005 (Representative of 1990-2008) Since the end of the Cold

War the division in the United Nations is split more North-South (developed vs. developing countries) than

the early Cold War East and West communities. Europe and North America compose North.

References1. 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/VisComms5. E. Voten, et al., 2009.6. M.A. Porter, et al. Not. Am. Math. Soc., 2009, 56, 1082-1097 & 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).

Kevin Macon ‘10 is a Physics major

Amanda Traud is a graduate student in

Mathematics

Carolina Scientific

Advancements 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

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

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].

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

Cell Signaling Therapy - Hope for a Seemingly Hopeless Cancer

Abby Bouchon, Staff Writer

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

shown that the Ras/RAF cell signaling pathways are especially active in malignant melanoma, suggesting 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 within the Ras/RAF proteins, which suggests the cell line might rely more heavily on that signaling pathway (see Figure 3) [8]. Sorafenib was more

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 in inhibiting melanoma will increase, along with the possibility of finding an effective treatment. The future for cell signaling therapy looks bright as it continues to be developed to defeat malignant melanoma.

Melanoma by the Numbers5% 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.

References1. 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, 1500-1515.4. M. Purdue, et. al. J. Invest. Dermatol. 2008, 128, 2905-2908.5. A. Green, et. al. Int. J. Cancer. 2006, 120, 1116-1122.6. F. Meric-Bernstan, et al. J. Clin. Oncol. 2009, 27, 2278-2286.7. 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.

Abby Bouchon ‘13 is a Biology major

Figure 2. While melanoma is visible on the skin, it can quickly metastasize to other organs in the body.

Figure 3. Primary data from Sorafenib viability testing. As shown, at 20 µM Sorafenib successfully prevents the

majority of cells from continuing to metastasize.

Carolina Scientific

The search for effective pharmacotherapy to treat addictions to alcohol and other substances has

been an active area of research for the past few de-cades. One of the main biochemical pathways stud-ied in the development of these therapies involves the opioid receptors, which are also targeted by drugs such as morphine. These receptors are concentrat-ed in the part of the brain responsible for emotions, hunger, and breath-ing. The binding of a specific class of neu-rotransmitters called endorphins to these opioid receptors re-sults in a euphoric feeling; for example, β-endorphins, a sub-class of endorphins, have a stronger effect on the limbic sys-tem’s response than will morphine. A se-ries of psychological disorders, from ad-dictions to obsessive-compulsive disorder, have been attributed to altera-tions in this pathway [1]. Naltrexone (trade names Revia, Depade, and Vivitrol) is one such medication that has resulted from addiction treatment research. Like other addiction treatment agents, this multi-ring, non-narcotic compound (see Figure 1) targets a variety of opioid receptors and competitively in-hibits β-endorphins from binding to these receptors. Though originally developed for treating addiction to narcotics, naltrexone has found wider application to the treatment of, among other disorders, alcohol-ism [2]. While naltrexone initially found success in fa-cilitating treatment of alcohol addiction, it was soon found that not all patients responded to treatment equally. As early as 1996, different responses to nal-

trexone were associated with family history, suggest-ing genetic predisposition. Changes to the structure of µ-opioid receptors, another subclass of opioid re-ceptors, were suspected in altering their functional-ity. In particular, two single-base changes at separate locations in OPRM1, the gene that codes for this re-ceptor, have been intensively studied with respect to their influence on alcohol dependency. Interestingly,

there has been no link found between the polymorphisms (base changes) and alco-hol/drug dependency, even though these base changes could manifest different addiction treatment outcomes for medica-tions such as naltrex-one [3]. The Combined Pharmacotherapies and Behavioral Inter-ventions for Alcohol Dependence (COM-

BINE) Study sought to investigate the link between these OPRM1 polymorphisms and response of pa-tients with primary alcohol dependence to naltrex-one across two different therapeutic regimens. These were:

1. medical management alone, which in-cluded the dispensing of the naltrexone in addition to patient education that reviewed medication adherence and overall func-tioning, and2. medical management with combined be-havioral intervention, which added “cogni-tive behavior therapy, 12-step facilitation, motivational interviewing, and support system involvement” to the medical man-agement regimen. [4]

Mary La, Staff Writer

Helping to Break the Habit: Naltrexone and Alcohol Dependency

Figure 1: a) Naltrexone is a competitive inhibitor of a series of opioid receptors [3]. b) Morphine. Compare the structural similarities between naltrexone and morphine. These similari-ties allow naltrexone to competitively bind to the opiod recep-

tors that morphine and related substances target.

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The double-blinded study (in which neither the in-vestigator nor the subject knew who was in the ex-perimental and control groups) was coordinated through the Collaborative Studies Coordinating Cen-ter 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, dur-ing which study participants were evaluated on alco-hol consumption and craving after having been ad-ministered naltrexone or a placebo. The participants had to meet the DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) defi-nition of primary alcohol dependency; the DSM-IV characterizes substance dependence by the follow-ing:

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, us-ing, 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 al-cohol 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 drink-ing 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 evalua-tion [5]. In the 604 participants included in the phar-macogenetic analysis, it was concluded that patients who had a copy of a specific one of the polymor-phisms mentioned above exhibited better naltrexone response and improvement in decreasing alcohol de-pendency [4]. It is important to remember that naltrexone is not the magic bullet that can completely and permanent-ly 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 oth-er comparable investigations can be used to tailor courses of therapy for patients suffering from addic-tions 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 pharmacoge-nomics of other medications used to treat similar dis-orders in general, and this field of research should remain of high interest for years to come.

References1. T. Scheve. “What are endorphins?”, 2009, <http://health.howstuffworks.com/human-nature/emotions/happiness/sci-ence/endorphins.htm>2. J.R. Volpicelli, et. al. Arch Gen Psychiatry, 1992, 49, 876-880.3. 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>.

Mary La ‘11 is a Chemistry and

Computer Science double major with a

Spanish minor

Figure 2. 3-D representation of Naltrexone.

Carolina Scientific

Amidst a sea of rumors about harmful chemi-

cals leaching into our Na-lgenes, and stainless-steel water bottles becoming the new fad, skeptics now have concrete evidence to turn to. A recent study con-ducted in part by UNC’s Gillings School of Global Public Health has found a link between Bisphenol A (BPA), a common pollutant in plastics, and adverse behavioral effects on young girls. Researchers found that daughters of women who were exposed to high levels of BPA during their pregnancy expressed more hyperactive and violent behaviors in early childhood [1]. The study, published in Environmental Health Perspectives on Oct.6, was conducted by researchers from a myriad of universities, including UNC, Simon Fraser University in Vancouver, B.C., and University of Cincinnati. Urine samples were collected from 249 pregnant women in Cincinnati, OH, at staggered intervals during their pregnancies. Researchers mea-sured BPA concentrations in each sample, and then assessed the children for behavioral problems when they turned 2 years old, using the Behavioral As-sessment System for Children-2 (BASC-2)[1]. This commonly-used analytical tool relies mostly on rat-

ing scales from teacher and parent reports. Nearly 99 percent of the women had at least one urine sample that con-tained some amount of BPA. Daughters of moth-ers with the highest BPA levels were more likely to have high aggression scores, similar to those of a boy. The association was

even stronger when high BPA exposure was seen ear-lier in pregnancy [3]. BPA is an estrogen-like chemical that is common-ly used in the production of polycarbonate plastics and exposy resins. This includes the production of some types of plastic water bottles, canned food lin-ings, water pipes, infant bottles, and medical tubing. Human exposure to this substance is thought to come through the diet when it leaches into food and drinks through these containers [3]. According to the Cen-ters for Disease Control and Prevention, about 93 percent of Americans have detectible levels of BPA in their urine [1]. The new findings are consistent with previous studies with mice that found that BPA caused ad-verse neurodevelopmental effects on newborns and fetuses, as well as more aggressive offspring. “We wanted to know if there was a risk in humans

Rebecca Searles, Staff Writer

BPA: promoting aggressive behavior in young girls

Credit: http://www.goodhealth.com/articles/2007/08/06/nutri-tion_for_young_athletes_fueling_up_before_the_game

Figure 2. The molecular structure of Bisphenol A (BPA).Figure 1. The molecular structure of an estrogen.

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for neurodevelopmental problems,” said the lead au-thor of the study, Joe Braun, a doctoral student of ep-idemiology at UNC Gillings School of Global Public Health. “Study results indicate that exposure to BPA early in the pregnancy seems to be the most critical 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, anti-social activity) because of its estrogen-mimick-ing properties. Although estrogen is more promi-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.

“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. Research-ers are unsure why there is discrepancy between boys’ and girls’ reactions to BPA exposure [1]. Many government agencies in the U.S. and Cana-da 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 chemi-cals industry argue that the study is not thorough enough to sound alarm bells in the public, and that other factors may be at work in contributing to the girls’ aggressive behaviors [2]. The FDA’s report on BPA’s safety is expected to be released in November [4]. Currently there are no requirements that BPA be listed on product labels, so it is difficult for consum-ers to avoid. However, one way to know, Braun says, is to check for plastics with the number 7 or 3 in the recycling symbol. These products are a known source of BPA [2].

References1. P. Lane. “Prenatal exposure to BPA might explain aggres-sive behavior in some 2-year-old girls,” 2009, <http://unc-news.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/2009-10-06-bpa-pregnancy_N.htm>.

Rebecca Searles ‘11 is a Biology and Psychology double

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

In 2008, Nalgene, a plastics company that sells water bottles, launched the “Everyday” line, which features a number of containers made from materials that do not

contain BPA.

Credit: http://www.backcountrygear.com/catalog/accessdetail.cfm/NA1007

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The development of a single zygote into an organism with

a brain is a process that has capti-vated scientists for centuries. One of these scientists is Dr. Andrew Lumsden, the director of the Medi-cal Research Council (MRC) Cen-tre for Developmental Neurobiol-ogy 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 scien-tists and staff are all dedicated to deciphering how the early stages of the brain develop. This sum-mer I had the opportunity to work in Dr. Lumsden’s lab and learn about his research into the devel-opment of the chick brain.

There are three layers of a verte-brate embryo- the ectoderm, me-soderm, and endoderm. The ecto-derm is the outermost layer which eventually becomes the nervous system. The first step in the de-

velopment of the nervous system is a molecular signal from the me-soderm 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 poste-rior side is where the spinal cord is located [2]. The specific structures in the brain develop from signaling cen-ters 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 fo-cused his research on these signal-ing centers. His early work was on rhombomeres, eight segments that make up the early hindbrain. These structures had been identi-fied in invertebrates, but little was known about their function. Dr.

Lumsden studied the chick em-bryo and noticed the same swell-ings 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 immunohis-tochemical techniques to identify where specific proteins were in each rhombomere. He found that there was an orderly pattern where each rhombomere produced dif-ferent proteins [3]. It was also dis-covered that in each rhombomere, HOX genes, the genes responsible for the structural development of an organism, are expressed differ-ently [2]. One of Lumsden’s key discov-eries about hindbrain develop-ment was that rhombomeres are

Dr. Andrew Lumsden

A nervous development: from neural tube to nervous system

Amy Abramowitz, Staff Writer

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

Credit: Nature

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lineage-restricted compartments where cells in one compartment do not migrate into another com-partment. 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. Lums-den found that when a single cell in a rhombomere divides, that cell and clones of it all stay in the same rhombomere. Using axon trac-ing he saw that each rhombomere develops into a different part of the hindbrain. Also each rhom-bomere 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 hind-brain. In particular, he has studied one structure that lies between the thalamus and prethalamus called the zona limitans intrathalamica (ZLI) that is actually a compart-ment itself. The ZLI, as seen in Figure 2, is involved in the de-velopment of the thalamus and prethalamus, the structures sur-rounding it. As opposed to the rhombomeres where different genes are expressed, the ZLI se-cretes one signal- sonic hedgehog,

a protein that acts on cells to form the thalamus and prethalamus. There is more sonic hedgehog re-leased 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 thala-mus and prethalamus [2].

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 comple-mentary RNA to the cell of inter-est. The probe binds to the gene of interest when annealed at the appropriate temperature and then a fluorescent marker can be ap-plied to visualize where the gene is located. In ovo electroporation procedure allows the phenotype of the embryo to be seen when

the gene is overexpressed. This is done by opening the egg and in-jecting 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 func-tion of the gene. In the future, Dr. Lumsden hopes to continue his research on the development of the nervous system and work toward applica-tion 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.

References1. 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.

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

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.

Figure 2. The ZLI can be seen in green.

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Mucus. 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 func-tion 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 suffi-cient to clear mucus from the lungs (if it were, you would be cough-ing 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 pic-ture. 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 overlay-ing 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,

ethanol, and orange juice; basi-cally 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 visco-elastic fluids. These are fluids that behave both like a solid and a liq-uid; 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 stat-ic 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 model-ing extremely difficult. Neverthe-

Keeping the BeatRanjan Banerjee, Staff Writer

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

Professor Richard Superfine

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less, understanding these proper-ties is essential to understanding the causes and treatment of many diseases. Many departments at UNC are involved in understand-ing these properties, including the biology, math, physics, and com-puter 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 pro-trusions. 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 simu-lated. 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 mu-cus movement occurs. From these

laboratory results, inferences can be made about how the system op-erates in the body, which in turn leads to insights on mucus clear-ance. 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 ad-dition, cilia are present in many

other locations in the body, such as the intestines and reproductive or-gans. By understanding the physi-cal 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.

References1. 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, 120-122.

Ranjan Banerjee ‘12 is a Biology and Physics double major

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

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

Credit: WebMD

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Frank Mu, Staff Writer

The word “colonosco-py” often forms the

base of many jokes and can bring out the rawest of emotions from even mentally tough individu-als. But the bottom line is that colonoscopies are necessary:colorectal cancer is the second leading cause of can-cer-related deaths in the United States and the third worldwide [1]. Over the past summer, I worked in Dr. John Lynch’s lab at the Uni-versity of Pennsylvania, helping to elucidate the pro-cess of how many colon cancers arise from the nor-mal epithelial tissue lining human intestines. The source of colorectal cancers comes from the initial development of benign precursor lesions (most commonly known as “polyps”) called adeno-mas in the colon [2]. As mutations accumulate in the cell, the polyps begin to form and at first are gener-ally innocuous. Progression along the adenoma-carci-noma sequence (Figure 1) describes the string of muta-tions required to overcome cell regulation [2]. Since the proliferation of each cell is regulated by several tumor suppressor genes, a few mu-tations may loosen prolifera-tion restrictions, but does not result in uncontrolled cell division. In order for a can-cerous tumor to form, there must be further progression

along the adenoma-carcinoma sequence, through ac-cumulation of multiple mutations [2]. Once normal colon cells undergo a malignant transformation, a tumor of cancer cells may develop. By this time cancer cells have acquired many capa-bilities that allow it to evade many of the regulations governing normal cell proliferation and homeosta-sis [3]. Often times, uncontrolled cell division leads to invasive colon cancer cells. Some may enter the blood stream, metastasize or spread to another part of the body, and begin forming another tumor. Mul-tiple tumors can quickly use up surrounding nutri-ents and disrupt the normal function of neighboring cells [3]. And since cancer cells evade apoptosis, cell death,they contain limitless replicative potential by mimicking signals that control proliferation path-ways [4]. In order to combat colorectal cancer it be-comes important to understand the pathways behind proliferation of normal intestine. One area of particular interest is the Wnt/β-catenin/TCF pathway (Figure 2), an important pathway lead-ing to proliferation and differentiation of normal colonic epithelium [2]. After the Wnt membrane surface receptor is activated, a series of protein ac-

Figure 1. The adenoma carcinoma sequence with initial polyp formation and progression to a malignant tumor [2].

Dr. John Lynch is the Assistant Director of the Undergraduate Student Scholars Program at the

University of Pennsylvania

A Scientific Callin': Probing Deeper into Colon Cancer

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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 tran-scription of certain target genes. Normal activation of these genes informs the cell to proliferate and di-vide [5]. Mutations in the Wnt/β-catenin/TCF path-way can result in constant high intracellular levels of β-catenin and constant stimulation of genes that start cell proliferation [3]. As a result, the pathway is always on, leading to un-controlled target gene expression, a common event in human colonic cancers. Though over-expression in the Wnt/β-catenin/TCF pathway leads to ma-lignant transformation, completely inhibiting the Wnt/β-catenin/TCF pathway is implausible: under-expression of the pathway results in malformation of the intestinal crypts required for absorbing nutrients [3]. Much of the focus of my summer has been deter-mining how this pathway is normally constrained in regular intestine. One important factor promoting differentiation and regulating proliferation is the homeodomain pro-tein Cdx2 [5]. This protein is found to play an impor-

tant role in many other model organisms in addition to humans [5]. Recent focus is directed at how Cdx2 interacts with β-catenin in the nucleus. Cdx2 has been shown to bind to β-catenin (Figure 3), thereby disrupting the β-catenin/TCF protein complex and inhibiting β-catenin/TCF transcriptional activity [5]. However, the mechanism by which Cdx2 attaches to β-catenin is still unknown. Undoubtedly, fully under-standing how Cdx2 plays a role regulating β-catenin/TCF transcriptional activity has important implica-tions in the field.

References1. 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 (Else-vier, 2006).4. A.R. Sepulveda et. al, in Cancer Genome and Tumor Micro-environment (Springer, 2009).5. R.J. Guo et al. J. Biol. Chem. 2004, 279, 865-875.

Figure 2. The activation of Wnt pathway when Wnt protein binds to membrane receptor. Mutations can cause the pathway to continuously be

active, though Wnt protein is absent [2].

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

Frank Mu ‘12 is a Biology and Economics

double major

~ Special acknowledgements to the Lynch lab and USSP

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What differentiates a patho-gen, a transplanted tissue,

and an embryo from one anoth-er? All are composed of foreign cells, but the immune system kills pathogens or rejects transplanted tissue, while accepting the grow-ing 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 com-plex aspect of nature that cannot be easily explained. The first answer to these ques-tions 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 pio-neering organ transplant research which led them to believe that a

certain mechanism which differ-entiates 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 func-tioned they laid the foundation to transplant immunology. Their insights led them to an obvious question, why weren’t babies re-jected like the transplants? This question introduced a fascinating new line of research: reproductive immunology. Reproductive im-munology is the study of how the body maintains immunity during reproduction and pregnancy, but avoids attacking the fetus. Dr. Steven L. Young, reproduc-tive endocrinologist and associ-ate professor at UNC School of Medicine, currently studies how

innate immunity (a branch of im-munology that uses receptors en-coded from the germ line) of the endometrium prevents an immune response from occurring during embryo implantation [1]. The en-dometrium 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 up-permost layer of the endometrium, which in turn, makes it the first to encounter pathogens or embryos. Due to its location, glandular epi-thelium is vulnerable to patho-gens such as herpes simplex virus (HSV), cytomegalovirus (CMV), and human immunodeficiency vi-rus (HIV) [4]. Thus it is critical for the endo-metrium to serve a dual function of protecting the reproductive tract from pathogens, while at the same time allowing implantation Figure 1. TLR receptors found in the human body.

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

School of Medicine

Reproductive Immunity:Toll-like Receptors in the Human Endometrium

Vahini Chundi, Staff Writer

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of the embryo. Dr. Young and his team believe that this dual-func-tion is done via an innate immune response in the epithelium using toll-like receptors (TLR). Toll-like receptors are leucine repeats with pattern recognition receptors (PRR) that allow them to identify pathogens. Toll-like receptors in turn produce cytokines which reg-ulate epithelial proliferation, pro-tect the immunity of tissue, and aid in embryo implantation [1]. Currently there are ten known toll-like 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 ex-pression of TLR mRNA using separated endometrial epithelial cells, stroma, and total endome-trium. 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. Re-sults 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 endome-trial 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, respective-ly. The high levels of TLR3 dur-ing the secretory phase (the last 14 days of the menstrual cycle during which embryo implantation oc-curs) suggest that TLR3 maybe involved in receptivity to embryo implantation. Furthermore, pro-gesterone (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 impor-tant for embryo surival, since it helps to detect viruses and stimu-late anti-viral immune responses. The way TLR3 detects viruses is by recognizing dsRNA (double-stranded RNA), which occurs dur-ing replication of most viruses [2]. Interestingly, Dr. Young has hy-pothesized that TLR3 also plays a role in embryo implantation. Thus the increase in endometrial TLR3 during the time of embryo implan-tation 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 toll-like receptors as protective agents, science has the potential to make many advances such as preventing miscarriages, making in-vitro fer-tilization more successful, treating or preventing endometriosis, and even help to explain infertility in women [4].

Figure 2. Endometrial lining.

References1. 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. Im-munol. 2004, 52, 67-73.4. R.L Jorgenson, et al. Hum. Immuno. 2005, 66, 469-482.

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

Chemistry minor

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Drink 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 consump-tion 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, pes-ticides, 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, inor-ganic arsenic, poses the risk for a multitude of cancers, cardiovascu-

lar diseases, skin disorders and re-cently investigated at UNC, diabe-tes mellitus [2]. Currently, the link between diabetes and arsenic con-sumption is under extensive re-search led by UNC research asso-ciate professor of toxicology and nutrition, Miroslav Styblo, Ph.D., both at UNC and abroad [3]. After finding a correlation be-tween 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 ide-ally, filters would be applied to all drinking water sources to prevent arsenic-induced health complica-tions, this process would be nearly impossible due to the scattered ex-posed populations and economic and cultural barriers. Alternative-ly, Dr. Styblo’s research seeks to achieve a more feasible way to

reduce the negative health effects. With his on-campus lab, recently named the newest Gillings In-novation Laboratory at UNC, Dr. Styblo aims to study the signifi-cance and effects of arsenic in its various metabolic forms on hu-man 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 inten-sities. It is believed that individu-als’ unique metabolism of arsenic may be the cause. From informa-tion 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 inter-fere with the mechanism by which arsenic triggers the development of diabetes and other health prob-lems. Similarly, in collaboration with assistant professor of nutri-tion, Dr. Zuzana Drobna, he has found that a modified diet, when combined with arsenic-based can-cer treatment, may improve the efficiency by which arsenic kills leukemia cells [3]. This inspires an optimistic outlook for the pos-sibility 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

Jesse Lomas, Staff Writer

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

Arsenic in Drinking Water?A Dietary Approach to Improving Arsenic-Induced Diabetes

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people in the world are exposed to arsenic in their drinking water, but considering the limited data avail-able, 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 bed-rock. Arsenic is also released into the atmosphere as a product of fossil fuel combustion [4]. Argen-tina, 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 suggested safe limit [2].

Did you know? In Bangladesh, arsenic was in-troduced to the drinking water in the 1970s when the UN drilled tube wells to provide a “clean” drinking water alternative to the prevalent use of surface water which contained parasites and bacteria. However, the wells were drilled into bedrock in which ar-senic was present in high concen-tration [3]. In order to hide this embarrassing oversight, doctors hid the results of tests from people with arsenic poisoning [5]. Translational Research: From the Lab to the People. Recent and ongoing research investigating the mechanism of arsenic-induced diabetes mellitus has revealed that this form of dia-betes 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 in-sulin’s signal to take up glucose from the blood, arsenic-induced diabetes mellitus causes glucose intolerance by different means

[6]. Previous research at UNC has pinpointed the specific step in the cascade of signaling that prevents glucose uptake in this specific type of diabetes and now tests are being done to investigate how diet-induced obesity and arsenic-induced diabetes may affect each other [3]. Results from lab tests on mice have shown that arsenic blocks obesity in mice but still re-sult in glucose intolerance from a source other than insulin resis-tance. Information from lab re-search is being translated to popu-lation studies in Mexico, where it is hypothesized that human obe-sity and exposure to arsenic has synergistic effects that result in more severe cases of diabetes [6].

Figure 2. Map of Bangladesh.

Figure 3. Mechanism of insulin resistance

in people with normal type II diabetes.

Credit: UCSF

References1. M. Silence. “Top 4 Benefits of Drinking Water,” 2006, <http://www.thedietchannel.com/Top-4-Benefits-of-Drinking-Water.htm>.2. “Arsenic in Drinking Water,” 2001, <http://www.who.int/mediacentre/fact-sheets/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 poi-soning: 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.

Jesse Lomas ‘12 is a Public Health-Nutrition major with a double minor

in Music and Spanish

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The 20th century was filled with breakthroughs in the field of

genetics. In 1953, Francis Crick and James Watson published their historic paper describing the struc-ture of DNA. In 1961, Marshall Nirenberg cracked the genetic code, showing that DNA is trans-lated 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 im-portantly, 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 ex-planation.

Dr. Strahl is one of the pioneers of the histone code hypothesis that offers one explanation on how genes are regulated [2]. The his-tone 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 pack-age the genetic blueprint into a sin-gle 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. DNA is coiled around the nucleo-

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 interac-tion or other histone-histone inter-actions, 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 phosphory-lation (addition of a -PO4 group) has been associated with coiling of DNA during mitosis [2]. These

Prashant Angara, Staff Writer

Dr. Brian Strahl, Associate Professor at UNC School of Medicine

Figure 1.In the first level of packing, DNA is coiled around histone proteins (yellow-green).

Histone H1 (pink) acts as a spacer between nucleo-

somes.[5]

The Histone Code Hypothesis

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histone modifications are the key to the histone code hypothesis [4]. The histone code hypothesis can be thought of as being analo-gous to the genetic code [2]. The genetic code states the DNA is translated in three base pair units (codons) and different combina-tions of these base pairs result in different amino acids. Similarly, the histone code hypothesis states that patterns of histone modifica-tions result in different expres-sions of the genes in DNA [2]. For example, if a histone was modi-fied in specific places, then a spe-cific protein that recognizes those modifications would then interact, thereby causing a change in bio-logical and/or DNA function (see Figure 1). Figure 2 shows some examples of modifications on var-ious histone tails. How exactly do we know that this is a valid hypothesis? Pres-ent research points toward this hypothesis being a valid one. For example, consider the phos-phorylation of histones. Histone phosphorylation, because it adds a negative charge, causes decon-densation of chromatin (unwind-ing DNA). However, a specific phosphorylation is also required for the condensation of chromatin (winding up DNA) needed dur-ing mitosis [2]. How is it possible that phosphorylation condenses and decondenses DNA then? One answer is that this histone modi-fication does not function alone; rather, multiple histone modifica-tions act in combination to spec-ify function. This hypothesis also provides an explanation for ex-ceptions to general histone modi-fication rules [2]. For example, acetylation is generally related with gene activation, but studies

in multiple organisms have shown that acetylation is also involved in transcription repression, function-ing in a completely opposite role. Silent loci in yeast have also been shown to be marked with acetyla-tion. However, if a code is being read, rather than single modifica-tions, it is possible that distinct enzymes act on the combinatorial sequence of modifications. With any research, there is al-ways the question of why is this important? Why is it so important that we decipher the histone code? The answer lies in the vast possi-bilities in the fields of medicine if this code is deciphered. Defects in histone-modifying enzymes have been linked to cancer, aging, neu-rodegeneration, drug addiction, viral latency, and stem cell biol-ogy [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 even-tually understand exactly how expression works so that one day, numerous health problems might have a solution.

References1. “Genetics & Genomics Timeline,” 2004, <http://www.genomenewsnet-work.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).

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].

Prashant Angara ‘12 is undecided in his major

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Garrick Talmage, Staff Writer

DNA 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 his-tones 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 Chemis-try Department, is in-terested in the meth-ylation of the amino 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].

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

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 chro-modomain, 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 re-press the expression of the gene surrounded by the histone [3].

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 characteris-tics 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 Chat-elier’s ideas to her advantage to synthesize the mol-ecule she wanted, using a new technique called Dy-namic Combinatorial Chemistry (DCC).

Figure 1. A tightly compacted nucleosome [2].

Figure 2. Methylation of

lysine.

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

Tag, you’re it! Discovering a new receptor to analyze gene repression

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Le Chatelier’s principle states that when a chemi-cal system is at equilibrium, the system will coun-terbalance any change that is made to it [4]. For ex-ample, 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 in-teract 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 character-istics. 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 equi-librium conditions, the thiol group from one mole-cule could bind to the thiol group from another mol-ecule, 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 combina-tions 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 re-ceptor 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 repeat-ed, 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 re-ceptor that would bind to methylated lysine [2]. The most exciting part about the resulting recep-tor 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 chro-mosome. 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 hope-fully Dr. Waters and Le Chatelier can contribute to it in a unique way.

References1. 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, 1025-1040.4. S. Zumdahl, in Chemical Principles (Brooks Cole, 2007).

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].

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

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Due to the crucial involvement of histones in cell proliferation and animal development through

DNA packaging and regulating gene expression, his-tone biosynthesis is of great interest. Of particular interest is the expression of histone messenger RNA (mRNA), which is intimately coupled to DNA syn-thesis [1]. In general, mRNAs are essential molecules in-volved in the translation of a genetic message (DNA) into a protein. These mRNAs are synthesized through transcription from genomic DNA [2]. Dur-ing the process of transcription, one strand of double stranded DNA is used as a template for constructing a complementary RNA sequence [3]. To become “ma-ture” 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 recog-nition and protection from enzymatic digestion (see Figure 1) [2].

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 re-quires just one unique processing reaction: single

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 in-volves many protein-protein interactions and several factors that are housed in the histone locus body, a subnuclear organelle that also contains re-petitive histone gene clusters [5]. 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 cleav-age 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 inter-actions, 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, in-cluding 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 Ta-tomer to study its role in histone pre-mRNA process-ing. As stated earlier, symplekin is a part of the cleav-age complex during pre-mRNA processing. This pro-tein is believed to function as a scaffolding protein, bringing together various proteins to position them in the larger processing complex [3]. To better un-derstand the role of symplekin in histone pre-mRNA

Michelle Lin, Staff Writer

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

Figure 2. Many proteins are involved in the cleavage of the

3’ end of the pre-mRNA.

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

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processing, Tatomer decided to examine where sym-plekin 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 lo-calizes 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 local-ized 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 symple-kin 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 mol-ecules from diffusing between cells. Proliferation is no longer occurring in fully developed and differen-tiated ovarian tissue and as a result, symplekin may be localized at the tight junctions instead because the histone processing factors located in the histone lo-cus 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 melanogas-ter larval imaginal eye discs. Imaginal discs, in gen-eral, 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, ima-ginal eye discs eventu-ally 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 ex-amining eye discs, we can compare and con-trast the localization of symplekin in prolifer-ating and differentiated cells and at specific points in the cell cycle all at the same time. These two different types of cells are sepa-rated by a morphoge-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 accu-mulation on the surfaces of the eye discs and there-fore 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 morpho-genetic furrow in cells at specific points in the cell cycle. Although progress is indeed being made towards understanding the role of symplekin in histone pre-mRNA processing, there is still much to be discov-ered and many other aspects of histone biosynthesis that are not fully understood. The drive to develop a comprehensive understanding of histone biosynthe-sis 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].

References1. 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).

Michelle Lin ‘12 is a Biology major

with a double minor in Chemistry and

Chinese

Figure 3. In Drosophila melanogaster, each larval

imaginal disc gives rise to a separate adult structure [10].

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If you have ever been that curi-ous 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 com-plete 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 par-ticular “star” in the sky, “zoom in” so we are directly overseeing its world, will we find the same pla-cidity? 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

a combination of billions of stars, representing a galaxy. Simply put, this galactic world is Chaos. Ca-lamity. Destruction. Marred by explosion after explosion. This is the world astrophysi-cist Gerald Cecil lives in—the world of Active Galactic Nuclei (AGN—A highly luminous gal-axy with a supermassive black hole at the center [1]). When as-tronomers 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 ear-ly 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) eject-ing highly energetic jets [1]. All of these phenomena comprise the study of “galaxy formation and evolution,” they are all manifes-tations of our Universe’s past, and have remarkably molded the Milky Way’s environment. “In or-der to understand how this whole system works, you need to under-stand these pieces and how they fit into the whole scheme,” Dr.Cecil comments. Dr. Cecil’s piece of the puzzle concerns another chaotic explo-sion—Superbubbles; They are gi-ant 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 and techniques to explore these Superbubbles. He has used the NASA Spacecraft, Chandra X-ray Telescope, and the Hubble space telescope to image these bubbles so that he can later analyze them with his team using spectroscopy and other techniques. “The inter-esting thing about these bubbles is,” Dr.Cecil says, “when you think of an explosion you think of parts flying everywhere like a bad science fiction movie, but this thing has a structure to it, you can

A Superbubble BathApurva Oza, Staff Writer

Figure 1. A composite image of Superbubble

NGC 3079 taken by Hubble Space

Telescope (HST). In the first two images the center nuclear

region is magnified, with the plus sign

indicating the active galactic nucleus

itself.

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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 spend-ing his time on spectroscopy and Instrumentation, building instru-ments so that he can better detect these bubbles with greater preci-sion. Cecil explains what keeps him motivated everyday: “Large-ly, that if you do the experiment right, with modern facilities, you see things that people have never

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 im-ages. Techniques such as spectros-copy, give additional physical in-sight. 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 superbub-bles. 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 out-wards creating a bubble-like co-coon around it, creating bubbles, Cecil explains. The leading theory suggests that superbubbles are triggered by hundreds of superno-va explosions, “ which are highly uncommon for a typical galaxy, but certain galaxies enter these ‘starburst phases,’ where stars ex-plode 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 Astrono-mers pick up on, that characterizes our current understanding of the Universe. It is these discoveries that let us know what is truly go-ing on beyond our misleading ce-lestial 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.

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

References1. 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.

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].

Apurva Oza ‘12 is a Physics major

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Genetic Divergence and Reinforcement of Species Differences

Elizabeth Bergen, Staff Writer

When closely related species come into contact with one another, whether due to natural oc-

currences 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 ani-mals, 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

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

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 require-ment 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 pop-ulations with sets of complex and interrelated math-ematical 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 demon-strated that reinforcement can operate under a broad range of biological conditions [1].

Dr. Maria ServedioAssociate Professor of Biology

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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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 or-der 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 per-sisted 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 devel-opmental factors. Sexual imprinting is a process by which an individual’s mate choice preferences are determined in part by their exposure to other indi-viduals. Dr. Servedio has examined how sexually imprinting on different targets affects the likelihood of speciation in birds. Among other findings, she

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

References1. 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.

Figure 2. When individuals vary in their ability to rec-ognize the notmal songs sung by conspecifics, aberrant

recognizers can diverge from the population’s norms and become fixed around a different norm [2].

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].

Elizabeth Bergen ’10 is a Biology major

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It’s 11 pm and you have an organic chemistry mid-term tomorrow. With an obvious all-nighter ahead,

an energy drink seems inevitable. When that bitter taste runs down your throat, and your eyes sudden-ly 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?

Energy drinks seem to be the key to surviving late nights in school and even the early mornings that follow. But what exactly are we consuming in the process? One of the most common ingredients in en-ergy drinks is taurine. Taurine, or 2-aminoethanesul-fonic acid, is a nonessential amino acid that is very abundant in the human brain. The commercial tau-rine found in most energy drinks, such as Red Bull, is a synthetically manufactured chemical. Research-ers at Cornell have discovered that in the part of the brain known to control sleep and wakefulness (the thalamus), specific receptors called GABA (gamma-aminobutyric acid) receptors may be strongly acti-vated by taurine [1]. These receptors are normally activated by a neurotransmitter called GABA, a mol-ecule that is known to have inhibitory effects on the brain [2]. Little is known about taurine’s exact ef-fects on the brain but they are said to be similar to the GABA effects, which is mostly neurological de-velopment and cell to cell connections. However, the Cornell researchers found that taurine seems to have more of a sedative effect on the brain and may play a

greater role in the “crash” after consumption. Another ingredient infamous in most energy drinks are the B vitamins, specifically B6 (pyridox-ine) 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 func-tions [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 vari-ous 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 mil-ligrams daily [4]. One can of Monster energy con-tains close to 60 milligrams of niacin. High doses of vitamin B3 can cause a burning sensation in the face or chest, which also causes “flushed” skin [5]. Ex-cess levels of this vitamin over a long period of time can cause liver damage and stomach ulcers as well. Thus, these vitamins should be ingested in modera-tion. More than one energy drink per day and several energy drinks per week can be a precursor to these serious problems. L-theanine is another ingredient now found uniquely in AMP© energy drinks which claim to sig-

Figure 2. a) Stucture of Vitamin B6. b) Structure of Vitamin B3.

Figure 1. Structure of Taurine.

Ameer Ghodke, Staff Writer

It’s Gonna be a Long Night...

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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 in-volved with L-theanine; however, studies have in-deed shown that L-theanine is related to increased alpha brain wave activity. This finding was conclud-ed in a study in which 13 people received 250 mil-ligrams 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 com-pleted 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 con-sume in excessive quantities. These three chemicals are consistently found in many of the leading com-mercial 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 modera-tion.

References1. J. Fan, et. al. J. Neurosci. 2008, 28, 106-115.2. R. Swenson, in Review of Clinical and Functional Neuro-science (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.

Figure 3. Structure of L-theanine.

Ameer Ghodke ‘12 is a Chemistry major

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

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Dr. 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 question-ing to begin.

His research is focused on chromosome segrega-tion, which involves cell replication and division. In mitosis identical cop-ies of the chromosomes segregate and produce two identical cells. In meiosis, the process by which sperms and eggs are produced, the chro-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 ten-sion 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

other disorders. There are 46 chromosomes in a hu-man cell and if even a single chromosome is improp-erly 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, “Ev-erything 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 eas-ily examine their mitotic cycle. He draws parallels between yeast and human cells because of the strik-ingly 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 con-served 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 se-quences and adding that DNA to yeast cells to alter them, giving the cell a function it did not previous-ly 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 un-derstand how these processes fail and how to cor-rect errors that arise. The ultimate goal would be to

Mary Gallo, Staff Writer

Yeast, A Human Stand In

Professor Kerry S. Bloom

Figure 1. Humans have 23 pairs of chromosomes.

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

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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 and the entire human genome has been sequenced; as Dr. Bloom said “we have all the parts for creat-ing a cell” but we can’t make a cell quite yet. Dr.

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

Mary Gallo ‘10 is an English majorReferences1. 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 be-comes 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

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.

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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.

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 1005Hear 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 col-laboration 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 previ-ous years are not eligible to apply for additional SURF awards. Students may not accept both a SURF award and a Burch Fellow-ship award for the same summer.

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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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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.

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.

NEED $$$ FOR A SUMMER IDEA?

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A Special Thanks To Our:

Michelle LinJesse LomasKevin Macon

Frank MuApurva Oza

Rebecca SearlesRohan Shah

Garrick TalmageAmanda Traud

Amy AbramowitzPrashant AngaraRanjan BanerjeeElizabeth Bergen

Abby BouchonVahini Chundi

Keith FunkhouserMary Gallo

Ameer GhodkeMary La

Staff Writers

Elizabeth BergenNatalia DavilaLenny Evans

Carolyn JohnsonAnn Liu

Frank MuRebecca Searles

Rohan ShahKristina Stanson

Production Staff

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.

“Research is formalized curiosity.

It is poking and prying with a purpose.”

~Zora Neale Hurston

Carolina Scientific Fall 2009Front 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.

fall 2009 issue

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