The George Washington University fosters a strong culture of undergraduate involvement in research and also of integrated, interdisciplinary research. Thus a number of our faculty has extensive experience in mentoring undergraduates and guiding them towards research careers.  Additionally with the number of faculty mentors, we have additional flexibility to place students in the most appropriate projects for their backgrounds and interests. The following is the list of proposed projects, in alphabetical order of faculty.

Robin Bernstein (Anthropology) and Sheri Church (Biology):
Aging in Great Apes: Variations in Hormone related Genes

Great apes have an extended period of postnatal development relative to other primates. It has been hypothesized that this extension is due in part to the activity of certain hormones during development. In particular, the shared pattern of postnatal increases in levels of
dehydroepiandrosterone sulfate (DHEAS) has been implicated as a marker of an extended “childhood” phase of development in humans and chimpanzees (Bernstein, 2005). This project will examine whether gene polymorphisms, which have been documented in humans as being associated with natural variation in levels of hormones related to growth and aging, are present and relate to the significant interspecific variation in these hormones found in the great apes. These analyses, coupled with hormone data from Pan paniscus, Pan troglodytes, Gorilla gorilla, and Pongo pygmaeus, will provide novel information about the physiological bases of interspecific differences in growth, development, and aging.

Ken Brown (Biology):
What are Neurotransmitters doing in Preneural Animal Embryos?

Catecholamines (dopamine, norepinephrine, epinephrine) and serotonin function in the adult animal nervous system as neurotransmitters; i.e., they relay nerve impulses. Our lab has identified these substances in both vertebrate (chicken) and invertebrate (sea urchin) early embryos that have not yet developed a nervous system. We are trying to determine the role of these substances in these pre-neural embryos. Our studies suggest that dopamine and norepinephrine play regulatory roles in heart development in chicken embryos, and serotonin stimulates cell movements and cell differentiation into specific organs in early sea urchin embryos (Anitole, et. al., 2004). The students will work on one of these two model embryonic systems to try and decipher the molecular mechanism of action of serotonin and catecholamines. They will use immunocytochemical techniques to determine the intraembryonic location of specific neurotransmitters. Since much of the sea urchin genome has been sequenced, bioinformatics techniques will be used to examine genomic sequences for putative serotonin receptor subtypes. This information should enable us to design studies to determine if these receptor genes are expressed and involved in serotonin-mediated cell movements and cell differentiation.

John Burns (Biology):
Rescuing DNA from Museum Specimens

The Order Characiformes and the family Characidae is very speciose and accounts for a major proportion of the freshwater fish fauna of Central and South America (Weitzman, et. al., 2005). Well-known members of this family are the piranha and neon tetra. It is extremely difficult, and in many cases now legally impossible, to obtain fresh specimens specially fixed for molecular studies. Our laboratory is currently investigating the possibility of “rescuing” formalin-fixed museum specimens for DNA analysis. Given the generally poor state of preservation of the DNA, most of the DNA that we are investigating involves mitochondrial DNA, which has many copies per cell, unlike nuclear DNA. Students will be engaged in all aspects of the study: isolation of DNA, PCR amplification, sequencing, bioinformatics comparisons, and phylogenetic analyses. Through this project, we will extend our collaboration with scientists at the Smithsonian Museum of Natural History.

Sheri Church (Biology) and Liliana Florea (Computer Science):
The Genetic Basis for Species Divergence in Sunflowers

We use a combination of bioinformatics and molecular approaches to determine what specific genes may be involved in adaptive differences between species as well how these genes have diverged. We focus in particular on sunflowers (Helianthus), a genus of native, agriculturally important plants (Lai, et. al., 2005). Students will learn to extract sequence information from databases, and also modify computer code to help search these databases more efficiently for our specific uses. Once the relevant genes are identified, the molecular component involves investigating the differences in these candidate genes between species of sunflowers. This includes analyses of DNA as well as expression of these genes. Students will also be expected to participate in the writing of manuscripts. Our experimental approach lends itself well to collaborations with GW scientists in other disciplines (e.g. Bernstein in Anthropology, and Florea in Computer Science).

Rob Donaldson (Biology) and Rahul Simha (Computer Science):
Analyzing Mass-Spectometric Data from Oxidized Peroxisomal Proteins

This project consists of a software development component in an interdisciplinary setting that is followed by a biological research component. The project mentor (Simha) has developed a Java program in collaboration with the PI (Donaldson) to help align mass spectrometry data from the PI's own studies in protein oxidation. The program is currently being used by the PI to make sense of the voluminous data produced from the many samples run through a mass spectrometer. However, like any bio-related software, the users (biologists) are interested in adding features specific to their needs. Both Simha and Donaldson envision a more enhanced version that performs aggregation and clustering, incorporates atomic weights from oxidative modifications, and most importantly, presents useful visualizations to biologists. This project is ideal for undergraduate students who have had some programming courses and will serve as the first part of the research project. The second part of the research project will involve developing and using clustering measures for data from proteins associated with the plant cell peroxisome. The goal is to identify those post-translational modifications that occur as a consequence of exposure to metabolic hydrogen peroxide in the peroxisome (Donaldson and Nguyen, 2005), the PI's own research area for several years. This project offers an ideal opportunity to work at the intersection of biology and computer science and to work both sides of a problem at this intersection.

Liliana Florea (Computer Science):
The Bioinformatics of Alternative Splicing

Alternative splicing, the process by which a gene can create multiple mRNA and protein isoforms by selecting different combinations of exons, is a growing area of research with the promise to explain how a limited set of genes can produce the large repertoire of proteins in the cell. Our research in this area is related to developing methods for annotating genomes with gene and alternative splicing information, and applying data-mining to further explore the regulatory mechanisms that control splicing (Florea, et. al., 2005). Students will be involved in analyzing EST spliced alignment data to identify alternative splicing events in animal and plant genomes, and will apply existing and newly developed methods to detect potential splicing regulatory sites. To test their methods, they will sequence and analyze EST data for selected genes in the (sunflower) genomes, and test the predicted splicing regulatory sites in the lab with gene reporter experiments. Additional students may choose to analyse gene annotation data from several Enterobacterial genomes to identify sets of orthologs, and use them to perform and compare various types of evolutionary analyses and to identify gene deletions, insertions and rearrangements among the genomes.

Patricia Hernandez (Biology):
Craniofacial Development using the Zebrafish Model System

Research in my lab centers around uncovering the developmental mechanisms involved in vertebrate head formation. I primarily use the zebrafish model system to examine the mechanisms involved in the morphogenesis of the pharyngeal arches and neurocranium. The vertebrate skull is composed of 3 basic units: the chondrocranium/neurocranium encases and protects the brain; the dermatocranium (composed of dermal bone) covers the neurocranium and makes up a significant portion of the cranial vault; and the viscerocranium, derived from seven pharyngeal arches, gives rise to the jaws and gill bearing structures in fishes. In mammals the viscerocranium consists of the jaws and associated structures, which support the throat and laryngeal structures. The pharyngeal arches in zebrafish embryos represent a series of relatively simple reiterated structures whose development depends on all three germ layers as well as neural crest cells. The relative simplicity of these embryonic structures affords an ideal situation in which to study the molecular mechanisms involved in the interactions among germ layers in these structures. Presently I am investigating the role of the Hedgehog pathway in the proper growth and differentiation of the cartilaginous components of the pharyngeal arches. Using mutant analysis, overexpression, and pharmacological treatment with cyclopamine my lab is investigating the role Hedgehog proteins play in the differentiation of the branchial cartilages (which support the gills). Our previous findings suggest that the Hh signaling pathway is required for growth of the jaws, hyoid and branchial cartilages, and more importantly it is required for the differentiation of branchial cartilages. Work on this project is ongoing.

Aleksander Jeremic (Biology):
High-Resolution Imaging of Amylin Aggregation and Signaling in the Pancreas

Insulin and amylin are two important pancreatic hormones that regulate glucose homeostasis in many organisms. Amylin is a 37 aa-residue peptide hormone, a protein co-expressed and secreted with insulin by islet beta-cells. In the late-onset diabetes, however, it comprises the major fibrillar component of the islet amyloid deposits, a hallmark of disease progression (found in over 90 % of patients). Diabetes is one of a family of diseases featuring fibrillar amyloid deposits, such as Alzheimer’s (beta-amyloid), Huntington’s disease (huntingtin) and mad-cow (prion) disease. Intervention to control fibril growth and aggregation has great therapeutic potential, but it requires a rational understanding of the molecular mechanisms governing fibril assembly and its dynamics in cells. Using the AFM, we recently performed nanoscale volume measurements, three-dimensional reconstruction and high spatial localization of the amylin aggregates on synthetic planar membranes. The goal of th is project will be to elucidate molecular events leading to the amylin aggregation and toxicity in pancreatic beta-cells. Students will have opportunity to image single beta-cell at very high-resolution using cutting-edge technologies such as the atomic force microscope (AFM) and laser-scanning confocal microscope (LSCM).

Diana Johnson (Genetics)
Genomes to Mendel and back—Identifying genes in the Drosophila genome sequence

Many genes were identified using classical genetic techniques based on causing a change in an organism’s appearance.  Bioinformatics approaches are used to identify genes in genome sequences.  This results in two parallel sets of gene data and there are many instances in which genomic sequences for genes need to be matched to the appropriate gene described by classical methods.  Using a variety of bioinformatics and genetic approaches, we are studying the identity of classical genes that appear to be involved in intracellular transport.  Having a sequence for these classical genes will increase our understanding of their functions and suggest possible ways to learn more about those functions.  We also explore, when appropriate, the evolution of these genes in a number of different species of Drosophila.  Students may be involved in any or all aspects of the study.  Techniques used include DNA and RNA isolation, PCR and RT-PCR, gene sequencing, using bioinformatics in comparative studies, and crossing Drosophila to localize the sites of genes relative to the genome sequence and crosses for looking at interactions between genes.

Randall Packer (Biology):
Signalling Pathways in the Mammalian Kidney

Our lab studies transporter proteins and the signaling pathways that regulate transport in the mammalian nephron. Our current experiments involve studies of regulation of those transporters and associated metabolic processes by hormones, including the renin-angiotensin-aldosterone (RAS) system and the collecting duct enzyme 11 β-hydroxysteroid dehydrogenase. These studies are aimed at obtaining a molecular-level understanding of how renal cells sense changes in systemic pH and respond by increasing the transport of acid and base equivalents from the renal tubule to the blood and of the role played by the RAS, especially direct effects of angiotensin II, on sodium transporters (Turban, et. al., 2006). Undergraduate students joining this research group will have an opportunity to gain experience in exciting investigative techniques ranging from working with whole animals to cutting-edge molecular tools. Students will learn how to conduct mass spectrometry-based proteomic studies as well as targeted proteomic approaches using a suite of specific antibodies to ion transporters known to participate in acid-base balance and ion balance.

Mark Reeves (Physics) and Akos Vertes (Chemistry):
Nanoscale Probes for Proteomics

Synthesis and characterization techniques from materials science have the potential to profoundly enhance our understanding of cellular systems. Research in our lab emphasizes the development of near-field techniques to focus light from the UV through the infrared to subwavelength-size spots. For living systems, these approaches make possible the imaging of fluorescent signals from features less than 100 nm in size and also the assaying sub-cellular features by ablation from in vitro cultures. A second area of research in our lab is to use self-assembly of nanoparticles (Diao, et al., 2005a & b)) to create new approaches to protein analysis. The resulting materials are being investigated as candidates for artificial gels (Turner, et al., 1998), for desorption substrates for MALDI-mass spectroscopy (Chen, et al., 2005), and for the electronic detection of proteins. In these projects, we are collaborating with Dr. Akos Vertes to develop novel approaches to characterize and understand living biological materials at the nanoscale. For example, these nanoscale detection schemes can be used to investigate protein function with a high degree of spatial and temporal specificity so as to enable a molecular-based understanding of subcellular organelles such as the peroxisome or of extracellular features such as the neuromuscular junction. Our experience with undergraduate researchers has shown that these projects provide an accessible introduction to research, where they learn, for example, to fabricate scanning-probe microscopy tips and to synthesize nanoparticles and assemble them into useful geometries. In this way, they learn fundamental concepts from nanotechnology while they are exposed to state-of-the-art characterization tools such as scanning electron microscopy and atomic force microscopy. At the same time, collaborations with GW faculty in the life sciences provide a cell-biology context for the scientific problems that the students will investigate. We have successfully mentored biology, engineering, and physics undergraduates in our lab.

Courtney Smith (Biology) and Liliana Florea (Computer Science):
Immunological Information in the Sea Urchin genome

We are studying an ancestral version of the innate immune system in sea urchins, the first line of defense against invading molecules. Our investigation is important because 1) echinoderms lack an adaptive immune response, which simplifies the investigation, and 2) the relationship between sea urchins and mammals makes our studies relevant for understanding the evolution of immune functions in the deuterostome lineage of animals that lead to humans. Recent observations suggest that invertebrate immune systems can generate responses that are significantly more diverse than had been imagined previously (Terwilliger et al., 2006). As a result, our data and those from a few other labs are changing the central paradigm of invertebrate immunology. Students will use basic molecular and cellular technologies, as well as bioinformatic and computational analyses of our large sets of sequence data. We are currently collaborating with Dr. Liliana Florea in Computer Science and Dr. Thomas Kepler, head of the Computational Immunology Lab at Duke University.

Akos Vertes (Chemistry) and Mark Reeves (Physics):
Laser desorption ionization from nanostructures

Laser desorption ionization mass spectrometry is a key method in the analysis of large biomolecules and a cornerstone of proteomics technology. The goal in these experiments is to efficiently produce ions from the molecules deposited on the surface of a substrate with minimal or controlled amount of fragmentation. It is also essential that the composition of the produced ions reflect the composition of the sample on the surface. In collaboration with Prof. Reeves from Physics we demonstrated that nanostructured surfaces such as thin films of gold nanoparticles can be successfully used in soft laser desorption ionization (SLDI) experiments. In other experiments the suitability was demonstrated for arrays of sharp conical nanoscale spikes (Y. Chen et al. 2006), or silicon nanowires (G. Luo et al. 2006). These surfaces have unique light absorption characteristics and can be used as efficient SLDI substrates, and in this project we plan to explore the energy deposition process into the analyte in SLDI from these surfaces. REU students can greatly benefit from working in this multidisciplinary environment, where they would learn basic methods of nanoparticle synthesis and the fundamentals of laser desorption mass spectroscopy. An example is Ms. Olesya Chornoguz, an undergradaute who joined my laboratory in 2003. She made sufficient contributions during her summer and school-year work to be a co-author and the presenter of posters at the 53rd American Society for Mass Spectrometry Conference and at the Fall 2005 ACS Meeting. After graduation she worked at Pacific Northwest National Lab and was recently admitted to the Graduate Program in chemistry at the University of Maryland.

Akos Vertes (Chemistry):
Order and Chaos in Electrosprays: The Electrified Dripping Faucet

Electrosprays have diverse applications including protein analysis, spinning of nanofibers and nano-encapsulation for drug delivery. In our research we have shown that a variety of electrospray regimes exhibit a fundamental analogy with the dynamics of a dripping faucet (Parvin, et. al., 2005). This simple system serves as a textbook example of temporal orderto-chaos transitions. We have demonstrated how applying high voltage to such a faucet changes the dripping behavior. While dripping faucets exhibit linear transformations in time-beat, their electrified counterparts show changes on a logarithmic scale. These differences stem from the behavior of the capillary waves on the liquid meniscus. Armed with this knowledge, we plan to boost the stability of electrosprays, thereby improve the reliability of the applications to peptide analysis by mass spectroscopy. Due to its broad appeal, this project is ideal for an undergraduate student. Some of the related methods are easy to comprehend and possible to learn within the limited time frame of an undergraduate research project.

Chen Zeng (Physics):
Computational (in silico) modeling of Protein Folding and Docking

One of the intriguing questions that motivate our research effort to develop a comprehensive computational protocol for designing novel protein folds is that nature appears to recycle about 1,000 distinct folds to make all proteins. Yet, there are about 100,000 different proteins in the human body alone and many more in the biological world. This apparent disparity between sequence diversity and structural diversity raises many questions that can only be answered if we know how various physical interactions are utilized to create stable protein folds. Our research efforts focus on developing and implementing computational algorithms that enable us to probe structural and functional properties of proteins in silico. Our current work examines the problem of designing small peptides as inhibitors for cyclin-dependent kinases to enable new types of cell-cycle studies (Agbottah, et. al., 2006). Undergraduates will first learn how to use protein structure visualizers to identify domains and their sub-structures; then, they will use our computational tools to search for folding patterns amongst the kinases, and for those peptides that dock onto specific protein sites. Students with modest computational background can also help modify the computer code to experiment with different energy functions.

Susan Gillmor (Chemistry):
Nanostructures in Biological Systems