HHMI Summer 2009 Research Program
Faculty Mentors & Projects

Malcolm CAMPBELL (Biology): Designing and Building Bacterial Computers
email Dr. Campbell

Students working in my lab will collaborate with math students in Dr. Laurie Heyer's group, as well as a team of biology and math students from Missouri Western State University – a collaboration funded by the National Science Foundation. Collectively, we will extend our synthetic biology research to design and build bacterial computers that can solve mathematical problems. Students will help design the project so the details are uncertain at this time. I encourage students who have completed their first year of college (i.e., Bio111) to apply because the molecular biology methods are easy to master, though older students are welcome too. The critical factor for success in synthetic biology is creativity, team-effort, and a willingness to learn by doing science. Campbell and Heyer expect to work with 4-8 student researchers in synthetic biology through a range of different funding sources. All summer students will compete as part of our 2009 International Genetic Engineered Machines (iGEM) team. A complete description of the summer 2008 iGEM project is available on our wiki: http://2008.igem.org/Team:Davidson-Missouri_Western More information about our past work is available on my web site: bio.davidson.edu/people/macampbell/macampbell.html#anchor3820996

Laurie HEYER (Math): Computing with Bacteria
email Dr. Heyer

The goal of this project is to harness the power of living cells to solve important problems in science and society. Students working with me on this project will collaborate with biology students in Dr. Campbell’s lab to design, build and test specialized biological devices to solve mathematical problems. Previous projects have used bacteria to solve problems in graph theory and cryptography. Students will have the opportunity to develop new applications for this year’s project. Potential real-world applications of our devices include energy production and medical treatments. We expect the Davidson team to consist of 4-8 students, with support from various funding sources, and we will collaborate closely with a team of 4-6 math and biology students from Missouri Western State University. Our interdisciplinary team will compete in the International Genetically Engineered Machines competition at MIT in November 2009. Students at all levels of educational experience are encouraged to apply.

Barbara LOM (Biology): Developmental Neurobiology
email Dr. Lom

Our lab has now combined developmental toxicology with transgenic zebrafish in order to develop an assay to examine how potentially teratogenic or toxic compounds influence the development of individual neurons. Transgenic zebrafish embryos engineered so that the jellyfish green fluorescent protein (GFP), which glows in the dark under fluorescent light, delineates neurons as they develop. Studies in our lab will examine how the pesticide malathion reduces neuron number and affects connectivity in the developing zebrafish spinal cord using laser-scanning confocal microscopy to evaluate cell cycle status and rates of apoptosis (programmed cell death).

Jeffrey MYERS (Chemistry): Folding & Misfolding of Myelin Protein Zero Mutants Implicated in Peripheral Neuropathy
email Dr. Myers

Human Peripheral Neuropathy is a class of debilitating diseases affecting the peripheral nervous system. Neuropathy is often the result of inherited genetic mutations in several genes that encode peripheral myelin proteins. The myelin sheath is a structure of multi-layered membranes that surrounds and insulates axons, greatly enhancing nerve conduction velocities. My proposed research focuses on myelin protein zero (P0), a membrane protein that plays a major role in the formation and maintenance of peripheral myelin. Several types of peripheral neuropathy are caused by mutations in P0 and over seventy disease-linked genetic mutations have been identified that alter the protein amino acid sequence. It has been established that at least some p0 mutants are mistrafficked or degraded in the cell, leading to lower levels of functional P0 in the myelin membrane. The hypothesis to be tested is that disease-linked P0 mutations lead to proteins that cannot fold properly (or are unstable) and are prone to aggregation (precipitation from solution). The folding, stability and solubility of wild type p0 and disease-linked mutants will be probed via in vitro biophysical experiments on purified samples. The ultimate goal of these studies will be to understand the link between a mutation and protein malfunction so treatments can be developed. For example, if mutants are found to cause destabilization of the native folded structure, small molecule drugs designed to bind and stabilize the folded state of the protein should be a viable treatment. Participating chemistry undergraduates will not just benefit by learning biochemical and biophysical research techniques, but contribute in a substantive way to medical advancement, hopefully stimulating their interest in future research projects at the interface of biology, chemistry, physics and medicine.

Julio RAMIREZ (Psychology): The Functional Significance of Brain Plasticity
email Dr. Ramirez

The primary research goal of our research program is to determine the functional significance of hippocampal sprouting after entorhinal cortex damage in rats. This model neural system exhibits a set of well-defined behavioral and morphological changes in response to deafferentation. Several recent investigations have implicated sprouting by the crossed temporodentate projection to the dentate gyrus of the hippocampal formation in behavioral recovery from unilateral entorhinal cortex lesions. However, the issue of whether these proliferated connections are indeed functionally significant is far from resolved. Students involved in the HHMI program would participate in on-going electrophysiological projects focusing on paired-pulse facilitation of the crossed temporodentate projection after its sprouting response has been accelerated by progressive entorhinal cortex lesions as well as on behavioral projects exploring the use of the delayed non-matching-to-sample task (an operant conditioning task) as an assay for the effects of bilateral entorhinal cortex lesions on mnemonic functions. The primary pedagogical goal of our research program is to broaden students’ knowledge and training in Neuroscience and to kindle an interest in and an appreciation for the issues with which neuroscientists are concerned. This additional experience will significantly improve the training of undergraduate students as they prepare for entry into careers in science, medicine, or public policy.

Sophia SARAFOVA (Biology): CD4+ helper T cell homeostasis
email Dr. Sarafova

CD4+ helper T cells are the coordinators of the immune response and their number and functional health directly correlates to the ability of an organism to fight off infection. In most mammals, the CD4+ helper T cells outnumber the CD8+ killer T cells, resulting in a CD4/CD8 T cell ratio greater than one. This ratio may decrease with age, but is usually maintained at one or greater throughout the life of the organism through the process of homeostasis (the balancing act between production, survival, proliferation and programmed cell death of cells). Thus, a decrease in the CD4/CD8 T cell ratio could indicate a potential problem in the homeostasis of the CD4+ T cell population that could lead to decreased ability to mount an immune response. In my laboratory we are trying to understand CD4+ T cell homeostasis by studying a mouse strain that exhibits an inverted CD4/CD8 T cell ratio (a ratio that is less than one) as early as 10 weeks of age. Interestingly, this inversion happens predominantly in the females. So far we have investigated the possibility that in this strain there is a decreased production of CD4+ T cells, which would result in an inverted CD4/CD8 ratio, but have found no evidence to support this hypothesis. In the future our efforts will be focused on investigating whether the CD4+ T cells in this mouse are functional and can survive, proliferate and resist programmed cell death as well as CD4+ T cells from normal mice with a CD4/CD8 ratio greater than one. We will take special care to document and match within each experiment the sex and the age of the experimental animals from both groups in order to minimize the number of variables during data analysis.

Mark SMITH (Psychology): Physical Activity and Drug Self-Administration
email Dr. Smith

Aerobic exercise produces a host of psychological effects that are negatively correlated with substance abuse and dependence. For instance, long-term voluntary exercise increases measures of self-esteem and well-being, and decreases measures of depression and anxiety. Moreover, epidemiological studies report that participation in activities that promote physical fitness is associated with a lower incidence of tobacco and substance use among adolescent populations. Despite these promising findings, remarkably few clinical and laboratory stories have specifically examined a potential causal relationship between aerobic exercise and a decreased propensity to engage in drug-seeking behavior. Using an animal model of drug-seeking behavior, we will evaluate the efficacy of aerobic exercise to (1) attenuate the escalation of cocaine intake under extended-access conditions, (2) prevent the dysregulated patterns of drug intake that emerge during a prolonged binge, and (3) decrease cocaine-primed and cue-induced reinstatement following a period of abstinence. This project will be the first systematic examination of the effects of exercise on a range of behavioral processes that are believed to be involved in the ontogeny of addictive behavior. As part of its translational appeal, the project will examine exercise as both a preventative intervention (i.e., before drug use has been initiated) and as a treatment intervention (i.e., after self-administration has been firmly established). Collectively, these studies should significantly advance our knowledge on how physical activity interacts with the endogenous reward system to alter sensitivity to cocaine and other addictive drugs.

Erland STEVENS (Chemistry): Synthesis of Nucleoside Analogues
email Dr. Stevens

Nucleoside analogs are often used as anti-viral compounds. Examples include penciclovir and acyclovir, which act as inhibitors of nucleoside polymerases and are active against certain herpes simplex viruses. Both peniciclovir and acyclovir have a 5'-hydroxyl group for incorporation into a growing oligonucleotide. The lack of an operational 3'-hydroxyl group effectively stops chain elongation during transcription. Our proposed nucleotide analogs will be constructed using an azide-enol ether cycloaddition, a reaction developed in our lab. The targeted compounds preserve features that allow recognition of polymerases (a 5'-OH and functionality for Watson-Crick base pairing) while preventing chain elongation (no 3'-OH). Variations will be introduced through changes in the penultimate, DCC-coupling step.

David WESSNER (Biology): Analysis of Reovirus Disassembly, Replication, and Pathogenesis
email Dr. Wessner

To initiate a productive infection, a viral particle must enter an appropriate host cell and then undergo some type of capsid disassembly event, thereby exposing its genome to the host cell machinery. It follows, then, that viral replication and pathogenesis are dependent on capsid disassembly. Previously, we isolated a series of reovirus mutants that exhibit increased resistance to ethanol. As part of a summer research project, Karen Hasty (’10) investigated the in vitro disassembly of these mutant viruses. She very clearly demonstrated that the mutant viruses exhibit altered disassembly patterns. Based on these results, we hypothesized that the mutant viruses also would exhibit altered replication kinetics. To begin addressing this hypothesis, Alex Greer (’08) and Samantha Sinclair (’08) optimized an assay allowing us to quickly determine viral concentrations. During the summer of 2008, Karen Hasty and Mallory West (’10) used this assay to examine the replication kinetics of the wild type and mutant reovirus strains. Surprisingly, the mutant strains do not exhibit altered replication kinetics under standard conditions. During this coming summer, the HHMI Fellow will continue these studies. More specifically, s/he will investigate how ammonium chloride, a known inhibitor of reovirus replication, affects the replication kinetics of the mutant strains. Additionally, we will begin to investigate the environmental stability of these strains. This research may provide us with insight into the forces affecting virus transmission and pathogenesis.

To download an application form, click here.