- Academic English Studies (ESL)
- Asian Studies
- Biochemistry/Molecular Biology
- Environmental Studies
- Ethnic Studies
- Exploration and Discovery
- French Studies
- Gender Studies
- German Studies
- Health Professions
- Hispanic Studies
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- Latin American Studies
- Mathematics/Computer Science
- Political Economy
- Political Science
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- Rhetoric and Media Studies (formerly Communication)
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’16/’17 Research Students
Dr. Norma Velazquez-Ulloa studies the role of the extracellular matrix in synaptogenesis. I am interested in the function of the extracellular matrix protein thrombospondin (TSP). Previous research in mammals has revealed that TSP is secreted by glial cells and facilitates synaptogenesis. To further understand how TSP promotes synapse formation, I am studying the role of a conserved homolog of TSP in the formation of the Drosophila melanogaster neuromuscular junction (NMJ). Using fluorescence microscopy, I will identify whether TSP affects synaptogenesis in the D. melanogaster larval NMJ by manipulating TSP expression. In addition, I will be characterizing TSP expression in control and mutant strains at both the mRNA and protein level.
CD47 is an extracellular membrane bound protein that is involved in many cellular processes, but it is most known as the “Don’t Eat me Protein”. This protein is overexpressed in most tumor cells, and high levels of CD47 in cancer cells has been correlated with decreased probability of survival for multiple types of cancer. CD47 binds to the extracellular protein SIRPα present on macrophages causing a biochemical cascade that causes the macrophage to avoid phagocytizing the tumor cell. My research involves using biochemical techniques to study the interaction between CD47 and SIRPα, and develop inhibitors that will will bind to the extracellular binding domains of CD47 and SIRPα and prevent their interaction.
Complex organisms differentiate cells into a variety of cell-types to accomplish a multitude of necessary functions. Neurons in your brain and white blood cells in your immune system are examples of cells differentiated into cell types. Often, cell type specific organelles, or “little organs”, are how a differentiated cell completes a cell type specific task. I am using the C. elegans’ gut granule to study the formation and behavior of cell type specific organelles. I am investigating how three proteins, GLO-1, WHT-2 ,and WHT-7, play a role in the formation and sub-cellular behavior of organelles during embryonic development.
I use zebrafish to study the mechanisms of Parkinson’s disease. In Parkinson’s, abnormal clumps of the protein alpha-synuclein are found in affected neurons - these aggregates are called Lewy bodies. How and why the alpha-synuclein protein clumps is unclear, and I express alpha-synuclein tagged with green fluorescent protein (GFP) in zebrafish in order to study this aggregation. Almost all alpha-synuclein found in Lewy bodies is phosphorylated at a specific site, and my work focuses on studying the implications of this phosphorylation. Specifically, I use immunohistochemistry and in vivo time-lapse fluorescence microscopy to visualize and analyze alpha-synuclein in both live and fixed zebrafish.
’12/’13 Research Students
I use the small soil nematode C. elegans to investigate the biogenesis of lysosome-related organelles (LROs). Specifically, I sought to identify the activating accessory protein (a GEF) for a highly conserved Rab GTPase necessary for LRO formation. Rab GTPases act as molecular switches and coordinate vesicle traffic within the cell; however they are not self-activating. Thus in finding the other protein(s) that ‘flick’ the Rab’s ‘switch’, I hope to further elucidate the LRO biogenesis pathway. I used a genetic bypass approach to find the GEF protein, which resulted in long nights listening to blaring pop music and moving mutant worms that were forever destined to roll in small circles. I plan to continue my work with Dr. Greg Hermann next year as his lab assistant before pursuing an MD./ Ph.D.
I am studying the multi-functional ribosomal protein S3 (RpS3), and its role in ribosome biogenesis in Saccharomyces cerevisiae. In particular, I am trying to map its binding site for Ltv1, another ribosome biogenesis factor, using the yeast two-hybrid assay. Large deletions make RpS3 unstable, so I have used PCR mutagenesis to generate point mutations, and then screened for loss of interaction with Ltv1. Point mutations that result in a loss of interaction between RpS3 and Ltv1 may have affected the structure of RpS3’s binding site or any of RpS3’s phosphorylation or sumoylation sites, which all have the potential to further our understanding of RpS3 and Ltv1’s interaction, as well as each protein’s role in ribosome biogenesis.
I am studying ribosomal biogenesis in the model organism S. cerevisiae. The
ribosome is the complex macromolecular machine responsible for all protein synthesis. The ribosome is composed of two subunits, one small (40S) and one large (60S). Of specific interest to Dr. Lycan’s lab is the small, or 40S, subunit’s biogenesis. Each subunit interacts with specific proteins, ribosomal and non-ribosomal, that aid its maturation and export. One such 40S non-ribosomal protein, or biogenesis factor, is Ltv1. My research focuses on the characterization of this protein’s interaction(s) with the small subunit. Specifically, my aim is to define its binding site for RpS3, a ribosomal small subunit protein. This interaction could prove integral to Ltv1’s role in 40S biogenesis and help to elucidate better models of small subunit export and maturation.
Long-term memory formation in the mammalian hippocampus results from synaptic changes that enhance neuronal communication. A key technique used in studying these changes is fluorescence microscopy, which allows researchers to visualize cellular proteins that are critical to facilitating memory formation. However, fluorescence microscopy is subject to the diffraction barrier, a limit to the resolution achievable through optical microscopy. My thesis has focused on applying two recently developed superresolution microscopy techniques, structured illumination microscopy (SIM) and photoactivated localization microscopy (PALM), which “break” the diffraction barrier to offer up to 20-fold greater resolution than is possible using diffraction limited methods. This increase in resolution has allowed me to address questions such as whether dense core granules, which carry the neuromodulatory proteins needed for long-term memory formation, traffic as individual granules or as clusters to synapses.
I am studying the design of novel protein inhibitors through the combination of computational design algorithms and rationally directed design strategies. The proteins that I am focusing on are the related proprotein convertases furin, which is over-expressed in many human cancers, and PC1. Both furin and PC1 are chaperoned by inhibitory prodomains until they reach their site of activity in the trans-Golgi network. My research focuses on using these inhibitory prodomains as a starting point in the design of new and more potent inhibitors of both furin and PC1.
’11/’12 Research Students
I am studying the biogenesis of a lysosome-related organelle, the gut granule, in the model organism C. elegans. Previous research in the Hermann lab has identified two genes, glo-1 and glo-2, that are involved in gut granule formation. To elucidate the specific role played by these two genes in gut granule biogenesis I am employing a host of genetic and molecular approaches. I am currently using the Yeast-Two Hybrid system to investigate genes that have previously been proposed to interact with glo-2. As well as inducing mutations to investigate genes that might interact with glo-1 and serve to activate it. Both of these approaches have the goal of further identifying the specific function of these gut granule biogenesis genes.
Christine Van Tubbergen
I am studying the polyamine pathway in the parasite Trypanosoma cruzi, the causative agent of Chagas disease. Polyamines, such as putrescine, spermidine, and agmatine, are compounds involved in the regulation of important cellular processes like the cell cycle, through which cells proliferate. The biosynthetic pathways of how polyamines are produced have been deduced in other parasites as well as humans, and differences in these pathways have been exploited as drug targets for the treatment of other parasitic diseases. However, the polyamine pathway in T. cruzi remains unknown and there is no effective treatment for Chagas disease to date. There are no known vaccines and current therapies rely on a few drugs, many of which are toxic to humans. In this project, I intend to use information from the T. cruzi genome, using bioinformatics to compare putative polyamine biosynthetic enzymes with other related parasites, such s Leishmania donovani, to piece together the polyamine pathway in T. cruzi. I will create knockout strains of T. cruzi that lack these putative biosynthetic enzymes to deduce which are required for survival of the parasite. I will also complement knockout strains of L. donovani lacking polyamine biosynthetic enzymes with the corresponding putative enzyme from T. cruzi. By doing so, I hope to gain a better understanding of the polyamine pathway in T. cruzi that will reveal potential drug targets for future research.
’10/’11 Research Students
I am investigating the molecular basis of memory formation in the hippocampus. The creation of long-term memories requires plasticity at sites of neuronal communication known as synapses. Select neuromodulatory proteins such as the protease, tissue plasminogen activator (tPA), act as essential mediators of this plasticity. While the majority of research has focused on post-synaptic tPA, recent data has suggested a role for tPA in the pre-synaptic processes of synaptic strengthening. Through the use of cultured hippocampal rat neurons, a modern molecular biological toolkit, and fluorescence microscopy, I hope to elucidate the conditions required for the pre-synaptic release of tPA. a more profound understanding of this specific process will serve as a building block in the construction of a comprehensive picture of memory in the human mind.
I am studying the biogenesis of a lysosome-related organelle, the gut granule, in the model organism C. elegans. Previous research in the Hermann lab has identified a novel gene, gle-2, that is involved in gut granule formation. To elucidate the specific role played by glo-2 in gut granule biogenesis, I am using the Yeast-Two Hybrid system to search a C. elegans cDNA library for genes that interact with glo-2. I am also using genetic techniques to characterize various mutant alleles of glo-2, with the goal of further identifying the specific function of the gene.
’09/’10 Research Students
Ribosomes are the macromolecular machines responsible for making proteins in living cells. While ribosome function is well investigated, less is known about ribosome assembly and transport. Of the two subunits that join to form a mature ribosome, the export of the smaller 40s subunit is of particular interest to our research group. I am currently working on the ltv1 protein that is attached to the 40s subunit during export. By utilizing fluorescence microscopy and GFP hybrids, I hope to see the effects of ltv1 mutations on the export of 40s subunits in yeasts.
This summer I used immunofluorescent techniques to study the intracellular localization of a recently discovered protein. This novel protein is generated by an alternative transcription start site within the ASPP2 locus. ASPP2 stands for Apoptosis-Stimulating Protein of p53-2 and is an important tumor suppressor frequently down-regulated in breast cancers. Upon response to DNA damage in healthy breast tissue, ASSp2 can contribute to a programmed cell death response which protects cells from accumulating harmful mutations. The new gene product I study is particularly intriguing as it is a truncated version of ASPP2. This difference in structure appears to affect its function as the protein is overexpressed at the mRNA level in breast tumors, suggesting that it promotes breast tumorigenesis and/or resistance to therapy. In the coming year, I will continue to examine the location of this potential oncogene in isogenic cell lines after exposure to different chemotherapeutic drugs.
My research is focused on the role of neuromodulatory proteins in long-term memory formation. Specifically, I am studying two neuromodulatory proteins, tissue plasminogen activator (tPA) and brain derived neurotrophic factor (BDNF), that promote changes in synaptic strength and are necessary for the early stages of memory formation. Using fluorescence microscopy and live cell imaging, we are investigating presynaptic localization of BDNF and tPA localization and the requirements for their release from synaptic sites in hippocampal neurons.
Spider venom is a complex mixture of small molecules, proteins, and peptides, many of which act as neurotoxins. Potential applications of venom peptides from other species, such as cone snails, have been shown in previous studies. Spider venom contains similar agents that could lead to the development of therapeutic drugs or biodegradable insecticides. I am currently working toward expressing and purifying a small toxin peptide identified from the venom glands of the spider species, Loxosceles hirsuta. The eventual goal of the research is to determine the structure of this peptide using nuclear magnetic resonance spectroscopy.
I conduct my research at OHSU in the lab of Dr. David Farrell, whose work centers on the role of fibrinogen in blood coagulation and angiogenesis. Fibrinogen is the main structural protein involved in clot formation during coagulation. I’m currently investigating the roles of intron splicing and polyadenylation in the regulation of a variant form of fibrinogen, which is believed to arise from alternative splicing. This fibrinogen variant stabilizes fibrin clots and may therefore be a previously unrecognized risk factor for heart disease.
My daily research experience consists of moving worms, allowing enough time for them to copulate before the males are killed, and then stealing their babies to examine new genetic combinations with a microscope. I use the model organism Caenorhabditis elegans, a small soil nematode, to investigate how the cell is organized into compartments. Specifically, I am studying the formation of a lysosome-related organelle called the gut granule. I am currently identifying and characterizing mutations that can restore compartmentalization when key components are disabled.
Spider venom contains hundreds of small peptides. Many of these peptides are neurotoxic and help the spider to capture prey and defend against predators. Furthermore, it has been shown that many of these peptides can act specifically against a wide range of neuronal targets. This diversity creates a potential library of small structures that could be utilized in the creation of pharmaceuticals or biodegradable insecticides. My research focuses on purifying a venom peptide isolated from a relative of the brown recluse spider, in order to determine the structure using solution-state nuclear magnetic resonance (NMR) spectroscopy.
’08/’09 Research Students
Spider venom contains a diverse mixture of small proteins some of which have been shown to be highly specific to the targets with which they interact. Their high specificity makes them potential leads for biodegradable insecticides and pain relievers. I am currently working to generate and purify a sample of a toxin protein isolated from Loxosceles hirsuta, a relative of the brown recluse spider, in order to determine the structure using solution state nuclear magnetic resonance spectroscopy.
This fall, I will begin a PhD program in Chemical Biology at the University of Michigan and focus my studies on protein structure-function relationships and methods of protein structure determination.
I work in Deborah Lycan’s lab, and we are interested in ribosome biogenesis. Ribosomes are the molecular machines within cells that are responsible for protein synthesis. I use genetics, fluorescent microscopy, and biochemistry to study nuclear export of the small ribosomal subunit in the budding yeast S.cerevisiae.
I will be attending UC Berkeley in the fall to begin a PhD program in Molecular Biology.
I am currently conducting research germane to the molecular and biochemical events that underlie long-term memory formation. In particular, my work is focused on a protein that plays a critical role in memory enhancement, brain derived neurotrophic factor (BDNF). Single amino acid polymorphisms of BDNF have been found to affect human memory by influencing the localization and secretion of BDNF. Utilizing live-imaging fluorescence microscopy and biophysical methods of analysis, I am studying the synaptic localization of BDNF and evaluating the dynamics of BDNF-containing granules at presynaptic sites in hippocampal neurons.
I have been studying bakers yeast (S. Cerevisiae) in Lewis & Clark’s Lycan lab for about three years. My current work explores how ribosomes, the large macromolecular machines that produce all protein, are exported from their place of birth in the cell nucleus to the cell fluid where protein is produced. My thesis research revolves around a single protein on the surface of the small subunit of the ribosome that appears to play a role in this process.
After graduation I will work for a year with MobilizeMRS.org, a venture that I founded to enable health workers in the most remote and overlooked communities to record medical data and perform $1 CD4 counts (CD4 count measures the progression of HIV), and send this data directly to a central electronic health record using mobile phones. At the end of this year I hope to attend medical school, and will pursue a career in academic medicine, global health, informatics, and social entrepreneurship.
The capability of neural networks to change over time underlies many crucial processes in the brain, such as long-term memory formation in the hippocampus. These systemic changes result from many individual synaptic modifications, which are carried out by a class of secreted proteins known as neuromodulators. One of these neuromodulatory proteins, which is necessary for long-term memory formation, is known as tissue plasminogen activator (or tPA). tPA, a protease, is thought to promote synaptic modification through its ability to cleave other proteins. My current work utilizes cultured hippocampal neurons, molecular biological tools, and fluorescence microscopy to investigate the presynaptic secretion of tPA.
I will be pursuing a PhD in Biology at Stanford University.
For my senior thesis I am studying the biogenesis of a specialized lysosome-related organelle, the gut granule, in C. elegans. Previous research in our lab identified a gene, glo-1, that is necessary for the formation of the gut granule. I am doing a genetic suppressor screen on glo-1 to identify other genes that are involved in the gut granule biogenesis pathway.
Next year I am attending UCSD medical school.
VGF is a protein that influences energy homeostasis and expression of this protein is upregulated during exercise. Recent work suggests that VGF is also implicated in learning and memory. I am working on a research project targeted at creating a DNA construct of VGF linked to a fluorescent marker protein EGFP. Once the construct is created we will determine where VGF is localized in neuronal cells and if it is copackaged with other key neuromodulatory proteins that facilitate long term memory formation.
Sage Coe Smith
I am currently researching the endosomal system within /Caenorhabditis elegans/ intestinal cells. I hope to elucidate the natures of several currently unclassified lysosome-like organelles. This will hopefully enhance the use of /C. elegans/ as a model system for the study of lysosomal storage diseases, inherited metabolic disorders caused by defects in lysosomes. Next year I am attending University of Washington Medical School.