Proceedings of the Biological Sciences Student Research Showcase 2010
LETTER FROM THE EDITOR
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ack in September, Dr. Gabriele Wienhausen approached me and the research editors of Saltman Quarterly with an intriguing challenge: to convey the amazing research contributions of undergraduates in a novel way, one that would be easily understood by a lay audience. Eagerly, we sought to synthesize the research presented at the 2010 Biological Sciences Student Research Showcase into cohesive articles and creative illustrations. We would bring the accessibility and intrigue of Scientific American and the Science Tuesday section of the New York Times to UCSD. In short, we would take our readers “under the scope” of exciting biological research conducted by undergraduates right here, on our university’s campus. Biology affects everyone, though everyone has a unique way of understanding the mechanisms governing his or her life. To that end, Under the Scope seeks to explain research not in overly technical jargon but in terms of its relevance to
everyday life, and, to explore how other disciplines can help us think of biology differently. There is clearly a reason why this past year, the UCS Division of Biological Sciences was ranked number one in the National Research Council’s assessment of over 5000 doctoral programs. In my opinion, that reason goes beyond the extraordinary strides we make in research to also include the innovative spirit with which we approach biology. Under the Scope, an expansion of the Saltman Quarterly Program, presents the work of student researchers, student writers and student artists alike. With this research brochure, it is our hope to begin a new tradition within the university’s already extant tradition of scholastic excellence and innovation.
Leila Haghighat Editor-in-Chief, Under the Scope
EDITORIAL BOARD
STAFF ADVISORS
FACULTY ADVISORY BOARD
WRITERS
ILLUSTRATORS
Editor-in-Chief Leila Haghighat
Associate Dean for Education Gabriele Wienhausen, Ph.D.
Immunology & Virology Steven Wasserman, Ph.D.
Cover Jane Rho
Senior Research Editor Tina Lu
Undergraduate Advisor Hermila Torres
Cell Growth, Development & Control Jim Wilhelm, Ph.D.
Junior Research Editor Lawrence Ku
Media Specialist Katie Frehafer
Conservation & Ecology Heather Henter, Ph.D.
Amanda Schochet Anelah McGinness Angela Shen Diana Ponce-Morado Joseph Aleshaki Kailin Duan Kit Wu Milli Desai Rachel Maher Sonia Kim Varun Chaturvedi Vidhi Jhaveri
Production Editor Nishita Shah
Physiology & Metabolism Kathleen French, Ph.D. Brain, Mind & Neurological Diseases Andrew Chisholm, Ph.D. Jill Leutgeb, Ph.D.
Articles Nicole Oliver
TABLE OF CONTENTS 4 5
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4 Our Body’s Defenses
12 You Are What You Eat
7 Unlikely Allies
16 Mice, Memory and Multiple Sclerosis
9 Living Under the Sun
20 Biological Sciences Student Research Showcase 2010
Exploiting the mechanisms by which viruses and other pathogens attack our cells may lead to better defense in the battles waged by our immune system Applying our knowledge of self-propagating stem cells to cancerous cells helps us to better understand the progression of cancer Understanding the complex relationships that interconnect the many ecosystems in San Diego can help us preserve our environment.
Digging deeper into the physiological mechanisms governing our metabolism may enable us to attack our nation’s obesity problem in a whole new way Delving into the intricacies of the human nervous system will unlock the mysteries of where memories form and how disorders like multiple sclerosis may be treated Abstract List
OUR Body’s DEFENSES
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The
enemies are approaching. Some
are
stealthily camouflaged and have already breached the barriers of the castle, but the battle has only just begun.
The
fortress,
armed and ready for defense, sends countless counterattacks on the enemy while keeping the walls fortified.
T
he scene described may seem to have come straight out of Lord of the Rings, but the human body is very much like a castle. Every day, it protects itself against microscopic enemies such as viruses, bacteria and cancer cells. This past year at UCSD, much research has been conducted on how these pathogens launch an attack and how the body responds in defense. New research has allowed us to better understand the structure and genetic makeup of pathogens in order to develop counter-measures against them. In the Virgil Woods and Joseph Vinetz labs, undergraduate researchers attempted to identify and create models of proteins involved in facilitating infection and use them to ultimately create a drug or other defense mechanism. Both Henry Guan and Patrick Hancock used mass spectrometry to identify different viral proteins as a step towards determining their structure. In another study, Brian Wong attempted “to map antibody epitopes in order to design immunogens that boost effective antiviral immune response.� Scientists believe that identifying viral proteins will be key to creating effective drugs against deadly viruses. Researchers elsewhere at UCSD are taking a different
approach to identifying viral proteins through their study of proteases, which are enzymes that digest proteins. Kenneth Petterson of the Vinetz lab focused specifically on a prevalent human disease: malaria. According to his study, the protease Plasmepsin X plays a key role in helping the malaria parasite, Plasmodium falciparum, infect the body. Students involved in this
Photo courtesy of http://newsroom.ucr.edu/2262
Blood infected with malaria. Stained purple cells are infected with the parasites. IMMUNOLOGY & VIROLOGY
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Photo courtesy of http://hiv.boehringer-ingelheim.com/com/HIV/Information_material/Images3.jsp
Dendritic cells are the link between the body’s innate and adaptive immune systems. Their spindly projections are used to take up peripheral pathogens, such as the viral particles shown here in red, and present them to B and T cells in the lymph nodes.
experiment aim to express active forms of the aspartic protease in order to understand its function and ultimately create an antimalarial drug. The detrimental illnesses that result from powerful pathogens such as viruses or bacteria are troubling, especially as we hear more reports of bacterial strains developing antibiotic resistance. The rise in antibiotic resistance has spurred interest in alternative treatments such as bacteriophage therapy. Bacteriophages, or viruses that attack bacteria, have the advantage of targeting only specific strains of bacteria. Therefore, they are unlike antibiotics, which may kill off harmless bacteria during the course of antibiotic treatment. A freshmen class of phage hunters have sequenced the genome of bacteriophages with hopes that one day, the data will be used to identify potentially useful genes for future applications against bacteria that have already developed resistance to antibiotics and other drugs. Students from BIMM 171, the phage genomics course headed by Drs. Kit and Joe Pogliano, have organized field guides of phage clusters, grouping together phages with similar genetic components. The Poglianos
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hope to identify the unique properties of each cluster. With the emergence of more and more drug-resistant strains of bacteria such as Methicillin-resistant Staphylococcus aureus (MRSA) and multi-drug resistant tuberculosis (MDR-TB), researchers foresee phage therapy being the next revolutionary treatment. The aggressiveness of diseases caused by viruses and bacteria pales in comparison to one of our most lethal enemies: cancer. According to a study in the Eyal Raz lab however, our bodies may possess previously undiscovered natural defensive measures. One undergraduate researcher in the Raz Lab, Amy Triano, noted that neurons containing transient receptor protein (TRP) ion channels in the connective tissue of the gut can help detect inflammatory damage of the gut. The pain receptors in these channels process thermal, mechanical and chemical stimuli. According to Triano, because inflammation of the gut is “associated with an increased risk of tumor development and growth in the colon,” the study’s specific aim was “the activation of TRP channels on regulation of the growth and malignancy of colorectal carcinomas induced by azoxymethane and repeated administration of DSS (colitisassociated cancer).” Future developments based on this research may prove to be vital in the combat against colon cancer. UCSD undergraduates are at the forefront of the cuttingedge research on how pathogens attack and how the human body responds in its defense. Using a variety of tools such as mass spectroscopy and phage therapy, researchers are making significant progress in identifying the structures and the modes of attack used by pathogens. It is with these contributions that we are beginning to understand the amazing ways our bodies work to defend the invisible enemies we encounter each day. Although we may not be aware of it, there is always an ongoing battle between pathogens and our bodies’ defenses in keeping us alive and healthy. WRITTEN BY ANGELA SHEN & KIT WU. Angela Shen is a General Biology
major from Thurgood Marshall College. She will be graduating in 2013. Kit Wu is a Human Biology major from Sixth College. She will be graduating in 2014.
UNLIKELY ALLIES by bringing together stem cells and cancer cells in the lab, UCSD researchers have opened the door for new and exciting approaches to cancer research
S
tem cells. Which keywords pop into your head right now? Common answers include science, politics, cures, treatments and cloning farm animals. Looking away from the politics and controversy, these special cells hold the potential to provide cures and treatments for a long list of diseases, including Alzheimer’s and Parkinson’s diseases. Now another human disease joins that group: cancer. The idea that cancer cells and cells with stem-like properties may be related to each other is the basis of a new and expanding field where researchers, including student researchers at UCSD, try to utilize their knowledge of stem cell biology to better understand the progression of different cancers. Known for uncontrollable cell growths and metastasis, cancer is currently treated with rounds of surgery, radiation therapy and systemic treatments like chemotherapy. The issue with radiation and systemic treatments is that they indiscriminately target rapidlydividing cells, including healthy tissue. Fortunately, recent findings and proposed concepts shed some insight into the disease itself. One such concept is the cancer stem cell hypothesis, which states that there is a small subpopulation of cells in cancers that have the ability to initiate and maintain malignant tumors. These cells are thought to originate from progenitor cells with stem-like qualities when key gene regulators are deregulated. These stem cells have the ability to self-propagate and differentiate and are
thought to be involved with metastasis and chemo-resistance. With increasing amounts of research invested in hashing out the finer details of cancer, some studies at UCSD focus on discovering and implementing drugs that may affect these cancer stem cells. One example of this is a research study conducted by UCSD undergraduate Katherine Blair, focusing on salinomycin and its effect on cancer stem cells in head and neck squamous cell carcinomas. Salinomycin is an antibiotic that functions as an ionophore to transport potassium across the lipid bilayer of cell
Photo courtesy of http://tgmouse.compmed.ucdavis.edu/jensen-mamm2000/BRCA-3/ BRCA-3.HTML
Microscopic view of cancer cells shows that the clusters of cells represent cancerous cells. CELL GROWTH, DEVELOPMENT & CONTROL
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membranes. This aids in killing breast cancer stem cells, though signaling in mouse mammary epithelial cells causes tumorigenic the actual mechanism is not known. Cancer cells exposed to or an abnormal increase in mammary growth, which provides salinomycin showed less sphere-like aggregate formation, which an implication for breast cancer. However, there is not much is a property of stem-cells. The study demonstrated that the drug evidence as of now that this is also true for humans.” For his own study, La demonstrated that the Wnt signaling was able to decrease the amount of cells that displayed cancer stem cell markers; however, the pathway that the drug took to pathway does play a role in the development of late-embryonic mammary glands, perhaps by increasing the growth potential negatively affect these cells is still yet to be determined. of the glands. In addition, Initially, it was believed that “So perhaps when thinking of stem cells, La’s data obtained from label the stem cell characteristics of a cancer cell are directly along with the politics, controversy and cloned retention methods suggest related to epithelial-to- animals, you will think of cancer as well, and that Wnt signaling and mesenchymal (EMT) transition, the amazing advances stem cells will be able quiescence indeed correlate with the development of which attempts to explain the to offer to cancer research and treatments.” mammary stem cell function. development of cells as they turn into mesoderm or the neural tube. However, Blair’s study showed Although there is not much evidence that Wnt signaling has a different relationship: as salinomycin doses increased, the EMT an effect in human breast cancer prognosis, La states that “the expression increased (a result detected by the presence of various research field of mammary stem cell and breast cancer is a very transcription factors related to EMT), but stem cell characteristics fast-paced and competitive field. New research information decreased. More research needs to be done to explain these seems to point towards the thought that breast cancers arise from results. This is the first study to question the seemingly direct deregulated and mutated mammary stem and progenitor cells. relationship between EMT and the stem-like phenotype of a cell. There is more and more supporting evidence for this.” Given that it is a recently-established and continuously Although this research is new and exciting, it has its challenges. Putative cancer stem cells are difficult to grow, and traditional expanding research field, the area of cancer stem cells has drugs such as cisplatin have a longer history of use and are better a promising future for those looking into improved cancer treatments. So perhaps when thinking of stem cells, along with understood, making them more attractive to researchers. While some researchers are utilizing the stem cell hypothesis the politics, controversy and cloned animals, you will think of to characterize new drugs, others are using this hypothesis to cancer as well and the amazing advances stem cells will be able to define which molecular pathways need to be disturbed to generate offer to cancer research and treatments. a cancer stem cell. Various molecular pathways are being probed to see if they play a role in the cause and prognosis of cancer, such as breast cancer. Wnt signaling, which directs mammary gland development, has been demonstrated to play a role in WRITTEN BY VIDHI JHAVERI & SONIA KIM. Vidhi Jhaveri is a breast cancer found in mice. Justin La, another UCSD student Physiology and Neuroscience major from Eleanor Roosevelt College. She will be graduating researcher, conducted a study on Wnt signaling and mammary in 2013. Sonia Kim is a Molecular Biology major from Revelle College. She will be gland development. He explains that “over-activation of Wnt graduating in 2012.
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living under the sun San Diego is home to a broad range of ecosystems. By conducting studies on terrestrial and aquatic populations, UCSD students are identifying the keys for sustaining this diversity.
E
cosystems provide humans with food, water and raw the details of the energy web’s components, from the foraging materials that we depend on for commercial products. For behavior of bees to the life histories of cacti, is essential to that reason, bees, phytoplankton and plant biodiversity preserving it. form a key part of multiple ecosystems. Bees provide humans Starting at the very bottom of the food chain, we have primary with food security by pollinating crops, which contribute to the producers, such as plants and phytoplankton, which consume growth of plant biodiversity, while phytoplankton are an important carbon dioxide and release oxygen. The health of phytoplankton is component of the food chain and help maintain high oxygen critical for preserving all aquatic populations as well as maintaining levels in the atmosphere. Their existence is crucial to human life clean air, since phytoplankton reduce CO2 concentrations. Elliot on earth. Students at UCSD are investigating ways to understand Weiss researched phytoplankton productivity by utilizing remote the important ecosystems that we admire and rely upon. In the sensing instruments, such as satellites, to analyze the ocean color larger scope, their findings may aid for insight on ocean health and climate. “Students at UCSD are investigating ways in establishing effective and costOn land, Marina LaForgia efficient conservation methods to understand the important ecosystems examined how changing concentrations to preserve living things and their that we admire and rely on...their findings of rainfall and nitrogen in soil affect environment. may aid in establishing effective and cost- Southern Californian coastal sage Simply put, ecology is the study efficient conservation methods to preserve scrub and chaparral growth. Sage of the relationships between living livings things and their environment.” scrub and chaparrals have adapted to organisms and their surroundings. endure harsh seasonal rainfall patterns Conservation is the protection of those relationships. On a in soils with limited nutrient availability. Future results from global scale, we can think of ecology as a giant interconnecting LaForgia’s study will show whether these plants are resilient to web of energy that relies on innumerable elements. Scientists are changes in precipitation, which can simulate potential effects due not certain about which factors of each ecosystem are ones that to climate change and heavy pollution. Another adaptation that are crucial to that ecosystem’s health and resilience in the face of many plants native to San Diego have is that their seeds do not human influences. Students at UCSD are exploring every level germinate during warm summer rains, when growing conditions of this great flow of energy in an attempt to better understand are not ideal. Rather, they only germinate after the cooler rains the mechanisms that drive ecosystem function. Understanding in the fall. Exotic annual grasses, which are invading the San CONSERVATION & ECOLOGY
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Diego landscape at a rapid pace, have seeds that germinate after the early summer rains. Master’s student Claire Wainwright sought to determine if the differences between native and exotic plants’ responses to seasonal rains contribute to the success of exotic annual grasses as invaders in Southern California. Invasive grasses pose a great threat to both the vibrancy of San Diego’s ecosystems and the health of the human population, while exotic grasses alter the fire regime of San Diego by drying out and dying during long rainless periods. Altogether, LaForgia’s and Wainwright’s research has shown
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that water and nutrient availability, as well as competition for space and resources, is important for the survival of plant populations in a common area. Their research will bring awareness to California’s plant ecology to further protect our diverse and dynamic ecosystem. Herbivores are the next higher-level members of our food chain. How important are herbivores for plants? That is what Amanda Schochet tried to figure out in her study. She contributed to a ten year study seeking to understand whether “bottom up” controls, such as nutrient and light availability, or “top down”
controls, such as herbivory, plays a larger role in determining the species composition and productivity of an herbaceous (nonwoody) plant community. This study is being conducted in herbaceous communities across the whole world, in areas as far away as China and Australia, so that ecologists can understand how herbaceous plant communities work at both a local and global scale. Douglas Hooten studied other animals that eat primary producers to get sugar, proteins and nutrients. He analyzed the distribution of three different kinds of cactus in the Mojave and Sonoran deserts that surround San Diego. This study contributes to our understanding of desert ecology by providing important information for cactus conservation. Cacti grow slowly, and, because scientists do not fully understand their growth patterns or how far they are distributed, they are unsure of how human activities, such as clearing land, will effect cacti populations. Hooten also studied the distribution of decaying cacti in each species. Their rotting tissue is eaten by none other than the fruit fly, the most beloved test subject of the biology world. Interestingly, closely related species of desert fruit flies are specially adapted to live on each cactus. Joel Schumacher investigated the evolution of one such adaptation, odorant receptors, which enable the flies to locate food and mates. Using an approach based on molecular biology, Schumacher sequenced the genes of two of the closely related fruit fly species. Scientifically referred to as Drosophila melanogaster, fruit flies are a critical genetic tool. Thus far, the genomes of twelve species of Drosophila have been fully sequenced. Their fast generation times make multigenerational studies, which would take hundreds of years if they were done on humans, easy. The Sonoran flies that Hooten and Schumacher studied have evolved to thrive in extremely harsh desert conditions and live off of alcohols produced by the flesh of rotting cacti, which are toxic to most other organisms. Understanding the genes that allow the flies to tolerate harsh conditions and toxic compounds as well as the
mechanisms that cause the flies to diverge into distinct species can provide us with extraordinary genetic insight. The honey bee is another insect that is critically important to humans. Honey bees are a vital part of our agricultural industry— most of the produce that we enjoy eating, like apples, grapes and cucumbers, as well as some of our most economically important crops, like soy beans and cotton, rely on bees to pollinate them. However, honeybees have recently been plagued by a mysterious disease called colony collapse disorder. The cause of the disease is still unknown, but researchers suspect that a combination of stresses, such as parasites, pathogens, pesticides and poor beekeeping methods, contribute to the disease. UCSD master’s student Daren Eiri investigated how sublethal doses of the popular crop pesticide imidacloprid affect the health of honey bee colonies. He found that bees exposed to imidacloprid are only motivated to feed on nectars with high sucrose concentrations. This “picky eater syndrome” may reduce the amount of nectar honey bees bring back to their hives, which weakens the colony. Finally, we reach the top of our web of energy, the “top of the food chain.” In this group, we have an animal that has very complex relationships with its ecosystem and that has affected its surroundings more than any other animal: humans. No, there were not any student experiments on humans this year, but every experiment featured has an impact on us. The students that shared their research at UCSD’s 2010 Biological Sciences Student Research Showcase offer a glimpse into the exciting worlds of ecology and conservation and give us a new perspective with which to view San Diego County. WRITTEN BY RACHEL MAHER, DIANA PONCE-MORADO & AMANDA SCHOCHET. Rachel Maher is a General Biology major from
Revelle College. She will be graduating in 2012. Diana Ponce-Morado is a General Biology major from Thurgood Marshall College. She will be graduating in 2012. Amanda Schochet is a Ecology, Evolution and Behavior major from Sixth College. She will be graduating in 2011. CONSERVATION & ECOLOGY
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you are what you eat This age-old statement has never been truer. By taking a closer look at how our bodies digest and use the food we eat, UCSD researchers are on their way to revolutionizing healthcare and solving the nation’s obesity problem.
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ichelle Obama, the First Lady of the United States, has decided to highlight a major health issue as her pet project. Following a trend of growing concern about health and fitness, Michelle Obama’s “Let’s Move!” campaign targets the problem of childhood obesity. According to her campaign, “Obese children and teens have been found to have risk factors for cardiovascular disease.” It reports that 60 percent of overweight children from ages 5 to 17 have at least one cardiovascular disease risk factor and 25 percent of them have two or more. Many fast food restaurants, which typically sell cheap but nutritionally unsound food, are located in financially poor areas. Children from lower socioeconomic neighborhoods are more likely to consume these unhealthy foods, and such obese children often become obese adults. Obesity has been shown to lead to ailments like diabetes and heart disease, and the nutritional variation between demoraphic groups means that
these cardiovascular diseases are more prevalent in the poorer populations, giving rise to health conditions that vary between different social classes and races. Thus, understanding how the cardiovascular system works goes beyond the idea of wanting to save lives; combating cardiovascular and metabolic diseases would also help even out the quality of health care received by different social classes and would promote equal and healthy lifestyles for all people. Michelle Obama’s campaign actively promotes prevention. If successful, it would provide an effective way to fight epidemics that plague so many Americans while also being cost-effective because it prevents the diseases from occurring in the first place. This approach is gaining wider support. For example, major cities within the United States are jumping on the bandwagon of addressing health issues to both increase the well being of their citizens and stem rising health care costs. In November 2010, San Francisco passed a law requiring fast food restaurants PHYSIOLOGY & METABOLISM
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in the city to specify the nutritional content of their kids’ meals before they can offer free toys with the meals. This effort to combat childhood obesity shows that science clearly does mix with politics. However, combating these deadly diseases requires an understanding of the underlying physiology and metabolism of the human body. At UCSD, students are embarking on various projects that contribute to Michelle Obama’s vision of a healthier nation. The steps to disease prevention must begin with the understanding of how our body’s mechanisms work, which is exactly what students’ research at UCSD entails. The two featured students below seek to understand a small aspect of this immense universe of the cardiovascular system in relation to the physiology and metabolism of our body. Diabetes, a condition of elevated blood sugar, affects a stunning number of Americans. In 2010, 11 percent of people ages 20 to 65 had diabetes, and 27 percent of people age 65 and older had the condition. It occurs in two distinct variations that have different causes. Type 1 diabetes is characterized by the body’s inherent inability to produce insulin from the beta
Simple changes in diet and lifestyle can help lower an individual’s risk for diabetes.
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cells of the pancreas, while the hallmark of Type II diabetes is insulin resistance. Despite the difference in their underlying pathophysiology, both Type I and Type II diabetes are often exacerbated by diets rich in sugars and fats. Based on this understanding, undergraduate researcher Di Fang found a unique angle for tackling diabetes at Dr. Gen-Sheng Feng’s laboratory in the UCSD School of Medicine. Fang worked to discover how beta cells, the cells which produce insulin, grow in the pancreas. The amount of sugar in our blood must be kept under tight control because sugar is our main chemical source of energy. The hormone insulin controls blood sugar level by causing cells to remove glucose from the blood. One common treatment for diabetes involves the administration of exogenous insulin. Diabetics can take insulin from an outside source to make up for the fact that their bodies have trouble making or responding to it. Fang’s research concentrated on an exciting new way to treat Type I diabetes. Fang worked with an enzyme called Shp2, which may have a positive effect on the regeneration of beta cells. Previous research on the subject has shown that the population of beta cells in the pancreas can increase if the body is under metabolic stress. For example, the metabolism of a pregnant woman changes to support the growing fetus. During this modification of her metabolism, new beta cells may grow and make her body better regulate blood sugar levels. Fang tried to determine how these new beta cells are generated and focused specifically on whether or not there is a “link between beta cell viability and Shp2.” Working with postdoctoral scholar Dr. Jing Wang, Fang hypothesized that Shp2 may play a role in causing beta cells to grow in mice. Previous research at her lab demonstrated decreased insulin secretion in Shp2-deficient cells. This means that, when beta cells lack the Shp2 enzyme, they produce less insulin, which could indicate that Shp2 has a direct influence on the survival of beta cells. Fang sought to determine whether treatment with Shp2
stimulates beta cells to regenerate in mice that have had their beta “Understanding the conditions of the illness and spreading cells removed. If her results show that Shp2 stimulates beta cell the knowledge to other people are essential parts in health care,” regeneration, the study could open the door to an entirely new said Sato. “Diagnosis is critical to detecting Kawasaki disease, and method of treating diabetes. misdiagnosis usually arises due to the lack of physical symptoms; Already, there is much discussion about providing diabetics we just do not know enough.” with healthy beta cells, particularly through the use of embryonic Based on his findings, Sato firmly believes his research can stem cells that may be induced to differentiate into beta cells. help lead scientists to finding a cure for this lethal disease. “There However, Wang says that “there are several obstacles, including is so much out there in translational medicine and so many ethical debates, to their clinical use, creating a need for new strategies mysteries within our body that we need to solve,” said Yuichiro. to generate beta cells in adult pancreas.” If the Shp2 enzyme “But the most important part of this particular research is that proves to be essential in it makes a difference, and the regeneration of beta “Understanding how the cardiovascular system works that is all that counts.” cells, this could usher in a goes beyond the idea of wanting to save lives; combating The results of Sato’s new way to treat diabetes cardiovascular and metabolic diseases would also help to and Fang’s research show that may even replace how basic research in the even out the quality of health care received by different laboratory may point the insulin therapy. The “Let’s Move!” social classes and would promote equal and healthy way to finding strategies initiative highlights the lifestyles for all people.” for clinical studies, targeted interrelationship between therapies and specific our diets, lifestyle and health. While diabetics can try to alleviate treatments for diabetes and many other cardiovascular diseases. their symptoms by controlling their sugar intake and exercising, Student researchers are not only advancing the scientific there is a certain limit to how much control they have over community but also the nation at large. The results of their their disease. This is where scientific research comes in. In the research provide essential tools for visionaries, like Michelle future, new medicines or discoveries may help better manage Obama, who desire to change the way we consciously think about or even cure diabetes. Researchers like Fang and Wang help tie our health and the biological mechanisms governing our bodies’ together scientific research and the active changes that we can physiology and metabolism. make to improve our lifestyles and health to give us new ways of approaching old diseases. Yuichiro Sato, another undergraduate student conducting research at UCSD, is investigating how biomarker proteins within the blood induce severe inflammation in children, a defective WRITTEN BY VARUN CHATURVEDI, MILLI DESAI & KAILIN DUAN. condition that is a precursor to acute Kawasaki Disease. Through Varun Chaturvedi is a Physiology and Neuroscience major from Revelle College. his research in Dr. Jane Burn’s laboratory at the UCSD School of He will be graduating in 2014. Milli Desai is a Human Biology major from Medicine, Sato discovered that biomarkers can critically serve as Revelle College. She will be graduating in 2014. Kailin Duan is a Human Biology major from Revelle College. She will be graduating in 2011. a laboratory test for Kawasaki Disease. PHYSIOLOGY & METABOLISM
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Memory, Mice and Multiple Sclerosis by delving deeper into the intricate nervous system, UCSD researchers are slowly unlocking the mysteries it holds
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f you’re a fan of movies like 50 First Dates, Finding Nemo, or Memento, then you’re familiar with short term memory loss, a phenomenon in which people with damage to the hippocampus are unable to make new memories. No matter how many times you introduce yourself to a person with short term memory loss, they can’t remember you. There are quite a few components to memory, and much research has been done to elucidate the role of the hippocampus in location or “where” memories, such as the site of the nearest gas station. However, less is known about how the hippocampus remembers “when” an event occurred. How does one remember how long it’s been since we saw a good friend? Why does the
smell of root beer remind you of an Italian restaurant from your childhood? At UCSD, undergraduate researchers have the opportunity to help answer questions like these as they investigate the role of the hippocampus in the formation of memory. In the lab of Dr. Fred Gage, Stephanie Alfonso’s work using genetically modified rats has been informative in the study of the hippocampus. This is one of the rare sites where new neurons continue to be born after one reaches adulthood–the other area is in the part of the brain used to sense smell. According to computer models developed in the Gage lab, these cells tend to lump together events that happened at the same time. Dr. Aimone, who advised Stephanie, gives an example of this BRAIN, MIND & NEUROLOGICAL DISEASES
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time association: “Years ago, when I was an undergrad, I bought the Beach Boys’ Pet Sounds album during the summer. Anytime I hear songs from that album, memories come flooding back about where I was living and my internship that summer.” This ability to relate memories to music is only one example of the role of the hippocampus. To test this model, Stephanie conducted experiments with mice chemically modified to lack the ability to create new brain cells. These mice were expected to be incapable of associating events that occur close in time. Indeed, while regular mice Hippocampal neurons play an integral role in memory formation. preferred exploring the locations of objects that were shown to them at the same time, the modified mice did not. The results of this work suggest more questions, and Stephanie’s work is feeling in his toes on the fateful morning of October 25, 2004. yet another important clue in solving the mysteries of temporal After all, as an experienced triathlete, Kyle was used to recovering memory. from a variety of injuries he had endured throughout his career. In the lab of Dr. Jill Leutgeb, Slayyeh Begum conducted However, things soon began to turn for the worse when, within a experiments in which rats performed the same foraging task twice matter of weeks, the cycling veteran couldn’t feel a single muscle a day. For each rat, the only difference was the time of day the below his waist. task was performed. These studies focused on the activity in areas Kyle was diagnosed with multiple sclerosis (MS), an of the hippocampus that specialize in “where” memories form. autoimmune disease that occurs when the body’s immune system There, they found a small group of brain cells that showed one attacks the fatty tissue called myelin that surrounds nerve fibers in firing pattern at 9 a.m. and a the central nervous system. As different pattern at 3 p.m. This “Vuong discovered that the receptors a result, most MS victims are provides evidence that the part left paralyzed since the neurons involved in inflammation became more of the hippocampus in charge in their muscles are unable to of remembering where things tolerant to the neuromuscular inflammation conduct or receive signals from are—the same part that taxi caused by MS. She describes this process to be the brain. Currently, there are cab drivers use to navigate the three main types of treatments streets of New York—may also ‘like how college co-eds…talk about building up a for MS patients: administering play a role in remembering what tolerance to alcohol and being able to drink more.’” medicine that manages time of day events happened. exacerbation or relapses of Slayyeh’s work will provide evidence to support further studies the disease, modifying the disease itself or providing drugs that in the formation of time-related memories in the hippocampus. modify the course of MS by altering or suppressing the activity Malfunctions of the mind can have very physical implications of the immune system. as well. David Kyle didn’t think much of the numbness he was Research conducted by Linda Vuong in Dr. Dennis Carson’s
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lab has produced promising results in alleviating the severe immune response caused by multiple sclerosis. Vuong used her knowledge of neuronal receptors and receptor binding in order to illicit a specific response from mice who were given a form of MS. To this group, she administered a receptor agonist, a chemical that binds to a receptor by mimicking a naturally-occurring substance. After low-dose injections of the agonist were injected in the mice each day for two weeks, Vuong discovered that the receptors involved in inflammation became more tolerant to the neuromuscular inflammation caused by MS. She describes this process to be “like how college co-eds…talk about building up a tolerance to alcohol and being able to drink more.” Vuong’s findings concerning the clinical importance of agonists to curtail MS inflammation present a new hope to victims such as David Kyle. The commitment of Vuong and others like her to research neuromuscular diseases has produced important medications that have facilitated David Kyle’s hope of returning
Picture courtesy of http://www.emedicinehealth.com/myelin_and_the_central_nervous_ system/page2_em.htm
In multiple sclerosis, T cells attack and destroy the myelin sheath, leaving the nerve cell fibers unprotected.
to his triathlon career. At the age of 39, Kyle continues to train for races and win competitions. He recently earned the title of Triathlon National Champion for disabled athletes in 2007. With the support of UCSD, young minds are being engaged in world-class research that will greatly impact our understanding of the fragility of the human nervous system. In the Ghosh lab, Joseph Antonios’ use of novel microscopy techniques is revealing new information about neuronal shape while Polly Huang of the Yaksh lab is studying the effect of botulism on pain receptors in mice. These insights into the way that the human mind works are utterly fascinating, but perhaps even more interesting is the study of what happens when the intricate circuitry of the nervous system malfunctions. Research about the hippocampus may elucidate more of the complexities of the aging brain, while experimentation with inflammation in animal models can lead to new medications for neuromuscular diseases plaguing young people. The breadth of neurological research is not limited to just this. Clearly, undergraduate research has the potential to shape the course of neurological research and revolutionize our knowledge of the brain, mind and neurological diseases.
WRITTEN BY JOSEPH ALESHAKI & ANELAH MCGINNESS. Joseph
Aleshaki is a Human Biology major from Thurgood Marshall college. He will be graduating in 2013. Anelah McGinness is a Physiology and Neuroscience and Spanish literature major from Revelle College. She will be graduating in 2013. BRAIN, MIND & NEUROLOGICAL DISEASES
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2010 Biological Sciences Student Research Showcase abstract list 20
UNDER THE SCOPE
Immunology & Virology (stem cells and the immune system and AIDS) Type-I IFN signaling is required for the maintenance of Foxp3 expression and Treg cell function Chang Kyung Kim Dr. Eyal Raz Canonical Wnt signaling and quiescence in embryonic murine mammary gland branching morphogenesis and stem cell function Justin La Dr. Geoffrey Wahl Functional characterization of zebrafish granulocytecolony stimulating factor Ryan Lau Dr. David Traver The role of TRP channel activaton in gut mucosal inflammation and tumorigenesis Amy Triano Dr. Eyal Raz Toscana virus nucleoprotein structure determination employing amide Hydrogen/Deuterium Exchange Mass Spectrometry Henry Guan Dr. Virgil Woods Structural and biophysical characterization of Lassavirus matrix protein Z using Hydrogen/ Deuterium Exchange Mass Spectrometry Patrick Hancock Dr. Virgil Woods The effect of schlafens on notch signaling Elaine Lin Dr. Michael David
Expression and characterization of Plasmepsin X, a Plasmodium falciparum aspartic protease Kenneth Pettersen Dr. Joseph Vinetz Structural study of deadly viral glycoprotein through Deuterium Exchange Mass Spectrometry Brian Wong Dr. Virgil Woods A field guide to the cluster A1 and E phage isolated by the UCSD phage hunters Roshmi Bhattacharya, Priya Chakrabarti, Aaron Kappe, Victoria Selzer, Alexandra Stanley, Oleg Stens, Yi Shuan Wu, Anne Lamsa Dr. Kit Pogliano and Dr. Joe Pogliano A field guide to the cluster B1 and F1 phage isolated by BIMM171 students Jeremy Chang, Mahathee Chetlapalli, David Horstman, Michael Pham, Andryus Planutis, Kyle Szeto, Cliff Wu, Anne Lamsa Dr. Kit Pogliano and Dr. Joe Pogliano The unidentified phage of the UCSD phage genomics course 2009-2010 Kristina Chun, Abby Conroy, Payal Desi, Hubert Jenq, Brittany Khong, Catherine Kuo, Joseph Steward, Anne Lamsa Dr. Kit Pogliano and Dr. Joe Pogliano Analysis of the Dot Product genome Andrew Grainger, Zac Hann, Lawrence Ku, Sean Lund, Amy Nguyen, Tasha Thompson, Lisa Zeng, Anne Lamsa Dr. Kit Pogliano and Dr. Joe Pogliano
Cytokines induce proliferation via an NCX-1 dependent mechanism Edwin Yoo Dr. Tomothy Bigby
Cell Growth, Development & Control (cancer, cell signaling, sleep cycles and circadian rhythms) Epidermal growth factor receptor overexpression contributes to the acquisition of stem cell like properties in head and neck squamous cell carcinoma and thyroid cancer cell lines Eric Abhold Dr. Martin Haas Functional significance of Mtm’s substrate selectivity Vignesh Raman Dr. Amy Kiger Bnip3 induces mitochondrial fragmentation via down regulation of mitochondrial fusion proteins Rita Hanna Dr. Asa Gustafsson Selective targeting of head and neck squamous cancer stem cells using salinomycin Katherine Blair Dr. Martin Haas Characterization of let-7 related microRNA primary transcripts and expression patterns in C. elegans Victoria Burton Dr. Amy Pasquinelli
Analysis of conditions for in vitro transcription with human factors Yanhua Chi Dr. James Kadonaga Bioinformatic analysis of bacterial mercury ion transporters Timothy Mok Dr. Milton Saier The role of TRPC and Na+/Ca2+ exchanger in mediating TGF946-induced pancreatic cancer cell motility Tiffany Ornelas Dr. Jimmy Chow Encapsidating mCherry into bacteriophage Hong Kong 97 immature and mature capsid Kristina Pedersen Dr. Jack Johnson Development of an ORF isolation protocol by expression of genomic clones in Nicotiana Tiffany Su Dr. Steve Kay Proline-23-Histidine (P23H) mutation in rhodopsin protein Mark Yu Dr. Jonathan Lin Inhibition of muscle phosphofructokinase-1 (PFK-1) and lactate dehydrogenase (LDH) by ascorbate derivatives: a proposal for cancer treatment Duyen-Anh Pham Dr. Percy Russell
ABSTRACT LIST
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Conservation and Ecology (wetlands, marine ecology, climate change and environmental studies) Photophysiological acclimation of Thalassiosira pseudonana under light limitation Elliot Weiss Dr. Greg Mitchell Spatial analysis of cactus plants and roots in El Saguaral, Mexico Douglas Hooton Dr. Therese Markow Variation in water use efficiency and soil moisture conditions of eight coastal sage scrub and chaparral species in relation to eater and nitrogen treatments Marina LaForgia Dr. Elsa Cleland Top-down versus bottom-up control on plant productivity and diversity Amanda Schochet Dr. Elsa Cleland Adaptive evolution of odorant receptors in cactophilic Drosophila Joel Schumacher Dr. Luciano Matzkin Cry5B: A crystal protein among a new and powerful class of anthelmintics Sophia Georghiou Dr. Raffi Aroian
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UNDER THE SCOPE
Picky eater syndrome: The pesticide imidacloprid on honey bee (Apis mellifera) alters sucrose response threshold and, potentially, colony health Daren Eiri Dr. James Nieh Seasonal priority effects: implications for invasion and restoration in California coastal sage scrub Claire Wainwright Dr. Elsa Cleland
SON DNA-binding protein homologues is crucial in zebrafish embryo development Xu Yao Dr. Dong-Er Zhang Investigation of the intracellular trafficking of ENaC subunits in colonic cell lines and dysfunctions of intracellular trafficking in cells exposed to the forskolin Angela Yu Dr. Kim Barrett Pancreatic Shp2 tyrosine phosphatase regulates beta cell mass in mice Di Fang Dr. Gen-Sheng Feng
Physiology & Metabolism (diabetes, digestive diseases, cardiovascular physiology and reproduction) Detecting novel protein interactions with Desmoplakin using yeast 2 hybrid protocols Patrick Lee Dr. Farah Sheikh The role of Dynamin in flies as a model for human centronuclear myopathy Jen Nguyen Dr. Amy Kiger Tbx20 as a downstream target of bonemorphogenetic protein (BMP) signaling in zebrafish heart development Richard Shehane Dr. Deborah Yelon
The role of G-Protein coupled receptors in regulating myofibroblast transformation Steven He Dr. Paul Insel Knockout and overexpression studies of human mitoNEET in synechococcus elongates Christina Homer Dr. Mel Okamura Circadian regulation of the mouse Kiss1r gene in GnRH neurons Lara Kose Dr. Pamela Mellon Utilization of radiolabeled transcript to perform nuclease assays to reveal detail about function of Ire-1 in RNA splicing Sari Lahham Dr. Maho Niwa
Characterization of two enhancers upstream of the Gonadotropin-releasing hormone (GnRH) gene Kathleen Yip Dr. Pamela Mellon
Structure-function study of protein-protein interactions between GIRK3 and the SNX27 PDZ domain Christopher Childers Dr. Paul Slesinger
The importance of matrix Metalloprotainase 9 in hypoxia-induced lung remodeling Mary Nguyen Dr. Gabriel Haddad
Development of hippocampal mossy fiber connectivity using serial-blockface scanning electron microscopy Joseph Antonios Dr. Anirvan Ghosh
Markers of cardiomyocyte injury in acute Kawasaki disease Yuichiro Sato Dr. Jane Burns
Brain, Mind & Neurological Diseases (Alzheimer’s and autism) A temporal code in the dentate gyrus: a unique role for adult-born granule cells in the formation of memories Stephanie Alfonso Dr. Fred Gage DSCAM and its role in the developing nervous system Eunice Kym Dr. Eduardo Macagno Identification of mechanosensory genes in Drosophila melanogaster Anh Nguyen Dr. Boaz Cook
Hippocampal network encoding of time-of-day in an episodic memory task Slayyeh Begum Dr. Jill Leutgeb
Up-regulation of chemokine receptor-like 2 in an in vitro model of cerebral ischemia Alice Chen Dr. Gabriel Haddad Mapping the mouse brain microvessel proteome Hyun Chun Dr. Brian Eliceiri Intrathecal botulinum neurotoxin B: effects on spinal primary afferent sensory C-fibers and nociception in the mouse. Polly Huang Dr. Tony Yaksh
A functional magnetic resonance imaging study of amygdalar activity in depressed adolescents Poonam Manwani Dr. Tony Yang Nicotinic receptors and the acetylcholine binding protein Phuong Thoi Dr. Palmer Taylor Establishing vertebrate model systems for the study of Gle1-mediated motor neuron disease Joseph Tsai Dr. Samuel Pfaff Toll-like receptor 7 tolerance in antineuroinflammation in murine experimental autoimmune encephalomyelitis Linda Vuong Dr. Dennis Carson
ABSTRACT LIST
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Under the Scope
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