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Individual student research projectsModern biology is a wonderfully broad and interdisciplinary undertaking. Accordingly, the projects available to students in the UC Berkeley NSF REU Site span the range from mutational studies of gene function to anthropological approaches to human evolution. Research interests of the participating faculty typically span disciplines, and many of the projects listed fall equally into two or more areas of cell, developmental or evolutionary biology. But to illustrate the general distribution of research possibilities across these three areas, we have grouped them according to the main focus of the research in the participating faculty laboratories, Cell Biology, Developmental Biology and Evolutionary Biology. For further information follow the links to individual faculty members web sites: Cell Biology David Bilder, Assoc. Professor, Cell & Developmental Biology, MCB Genetic mapping and analysis of tumorous mutants in Drosophila. An REU student would use genetic crosses to map the locations of potential Drosophila tumor suppressor genes, and also use immunohistochemistry to investigate the cell biological phenotype of mutants in these genes. These experiments will contribute to identifying new regulators of cell proliferation and cell organization. The student will learn techniques for Drosophila husbandry, planning and scoring genetic crosses, working with immunohistochemistry and fluorescence microscopy, plus concepts of genetic and phenotypic analysis. Zac Cande, Professor, Cell & Developmental Biology and Plant Biology; Director of Electron Microscopy Laboratory 1) Molecular and cell biology of meiosis in fission yeast. We study the process of meiosis in fission yeast and our goal is to understand how homologous chromosomes find each other in the nucleus, pair and undergo recombination. The student will help us clone mutants for chromosome organization and/or study their phenotypes using sophisticated light microscopy techniques. 2) Mitosis and pathogenesis in Giardia intestinalis, a basal eukaryote. This project involves studying cytoskeletal function during mitosis in the widespread intestinal parasite, Giardia intestinalis, a model organism for the study of evolution of the cytoskeleton and cell division mechanisms. The student will use immunocytological techniques and light microscopy to help us characterize mitosis and cytoskeletal dynamics in Giardia. David Drubin, Professor of Genetics and Division Head, Cell & Developmental Biology, MCB The dynamic linkage between the actin cytoskeleton and the endocytic machinery. The Drubin laboratory is studying the dynamic linkage between the actin cytoskeleton and the endocytic machinery. Real time imaging is being combined with modern molecular genetics and biochemistry. Depending on the interests and background of the student, opportunities will exist to learn about state-of-the-art fluorescence imaging of live cells, and/or about modern biochemical and molecular genetic analysis. These approaches will be used to analyze the dynamics of cytoskeletal proteins and endocytic cargo, and to reveal the mechanisms by which forces from actin polymerization are captured to promote membrane invagination and vesicle scission. Rebecca Heald, Professor, Cell & Developmental Biology, MCB Investigating mechanisms of spindle assembly. The REU student would perform mitotic spindle assembly assays using extracts prepared from eggs of the frog Xenopus laevis and investigate the role of a specific class of proteins that binds to microtubule plus ends. Effects of depleting these proteins on spindle assembly and anaphase will be tested, and biochemical assays used to identify interacting proteins in the extract. The mitotic spindle is the microtubule-based apparatus used by all eukaryotic cells to accurately segregate chromosomes. These studies will help to develop novel reagents to study the mechanisms of spindle function, and could form the basis for novel anti-cancer therapeutics. The student will learn to collect eggs and prepare extracts, perform cell biological assays, fluorescence microscopy and image processing, plus biochemical techniques. Bill Sha, Assoc. Prof, Immunology, MCB Toxoplasma gondii is a clinically significant protozoan parasite that can interconvert between a lytic tachyzoite form and a latent bradyzoite form within host astrocytes and muscle cells in humans. Although conversion between tachyzoite and bradyzoite forms, that mediate acute and chronic infection, respectively, is central to the pathogenesis of Toxoplasma gondii infection, relatively little is known about how the expression of host cellular genes affects conversion within infected host cells. Using an in vitro tissue culture system to study parasite conversion within human fibroblasts, host cell genes regulating apoptosis were found to regulate parasite conversion. This project will focus on understanding the cell-extrinsic mechanism of inhibition of bradyzoite conversion by the host gene Akt. Nilabh Shastri, Professor, Immunology, MCB. How does our immune system know if a virus is lurking inside an infected cell, if a cell has become cancerous or if an organ is transplanted from an unrelated donor? All these cells are different from our own normal cells, but the differences are often hidden deep inside the genome. Our immune system can nevertheless detect these differences because every cell is obliged to provide a full-disclosure of its protein contents on the surface. This obligation is met by a mechanism called "antigen presentation". Cells present antigens by first breaking up proteins into small pieces. The pieces are then taken to the surface by a remarkable chaperone called the MHC. We study the antigen presentation pathway from its beginning inside the cell to its end on the surface. We are particularly interested in the immunological consequences of mistakes in antigen presentation which allow tumors to escape detection or cause the immune system to turn against us. Karsten Weis, Professor, Cell & Developmental Biology, MCB Messenger RNA transport across the nuclear envelope. The export of messenger RNAs (mRNAs) from the nucleus to the cytoplasm is a key step in the gene expression of all eukaryotic cells. The projects uses a model eukaryote, the budding yeast Saccharomyces cerevisiae, to study the transport behavior and the shuttling dynamics of important mRNA export factors in living cells. Messenger RNA transport is a highly conserved process and insights obtained from these studies will be directly relevant to all eukaryotes, including humans. The student will create and express constructs encoding for transport factors tagged with variants of the green fluorescent protein to study mRNA export in yeast. S/he will learn various molecular and microbiological techniques to manipulate gene expression, fluorescence and video microscopy, image processing and general concepts of yeast genetics. Matt D. Welch, Professor, Cell & Developmental Biology, MCB Inactivation of kinesins in Trypanosoma brucei by RNA interference. Trypanosoma brucei is the causative agent of African trypanosomiasis (sleeping sickness). This neglected disease is a significant cause of death and morbidity in sub-Saharan Africa. The student will work with laboratory personnel to investigate the idea that microtubule motor proteins of the kinesin family represent good molecular targets for drugs to treat trypanosomiasis. The project will first involve amplifying and subcloning the genes encoding all T. brucei kinesins. Next, fragments of each gene will be introduced into T. brucei with the goal of inactivating the cellular copy of the gene by RNA interference. The student will learn molecular biology techniques such as PCR, restriction digestion, ligation, and DNA sequence analysis. In addition they will learn microbiological techniques involving the growth of both bacterial and protozoan cells in culture. Advanced students will learn biochemical techniques such as protein purification, and cell biological techniques such as fluorescence microscopy. Developmental Biology Sharon Amacher, Associate Professor, Genetics & Development, MCB Genetic and Genomic Analysis of Mesoderm and Somite Formation in Zebrafish. We are interested in how mesodermal tissue forms and differentiates during embryonic, in particular how the vertebrate segmental body plan is established during development, using zebrafish as a model system. Embryonic zebrafish cells are transparent; thus, we can follow cells over time in the living embryo. Zebrafish are also a tractable genetic system, allowing us to isolate mutants that perturb somite formation, and genomic tools are available that allow us to identify a large number of genes that are coordinately regulated during somite formation or are differentially regulated in mutant versus normal embryos. Of the several available projects, one involves mapping a novel zebrafish segmentation mutation to a region of the genome, with the eventual goal of identifying the gene disrupted by mutation and determining the normal role of this gene during development. Mapping will involve preparation of DNA samples from wild-type and mutant zebrafish embryos, extensive PCR analysis, running agarose gels, and analyzing the data. Once the gene is identified, a motivated student will be involved in determining when and where the gene is expressed during development using in situ hybridization. Robert Fischer, Professor, PMB. The primary goal of the research in my laboratory is to understand how gene imprinting is controlled. Alleles of imprinted genes are expressed differently depending on whether they are inherited from the male or female parent. In mammals, imprinted genes contribute to the control of fetal growth and development, and human diseases are linked to mutations in imprinted genes. In plants, imprinted genes control the growth and development of seeds, which are the primary source of carbon, nitrogen, and energy for humans and domesticated animals. In my lab, we are elucidating the mechanisms for plant gene imprinting, discovering fundamental differences in the regulation of gene imprinting in plants and mammals, and are showing how DNA is enzymatically demethylated. Sarah Hake, Director Gene Expression Center, Adjunct Professor, PMB Analysis of maize EMS mutants by genetics and microscopy. Student will be given a maize mutant that has not been characterized or mapped. The mutant will be planted at 3 different intervals so there will be a chance to see the mature form as well as capture early stages. Using bulk segregant analysis, the student will locate a rough map position for the mutation. If the mutant maps near a known mutation, complementation crosses will be initiated. Using scanning electron microscopy and histology, the student will try to determine the first stage at which the mutant deviates from wild-type. The student will learn genetics as well as have a sense of ownership with their own mutant. Iswar K. Hariharan, Professor, Cell & Developmental Biology, MCB Mapping genes that regulate growth in Drosophila. A fundamental issue in biology is how animal size is determined (e.g. why is an elephant bigger than a mouse?). We have studied this question by conducting an extensive genetic screen for mutations that cause tissue in the developing eye of the fruit fly, Drosophila melanogaster to grow excessively. A student working in the laboratory will utilize a combination of genetic and cell biological techniques to characterize these mutants. Genetic crosses will be set up with strains carrying markers and the frequency of different classes of progeny will localize the mutation to a specific region of the chromosome. Concurrently, the student will stain mutant tissue dissected from larvae to examine the mutant tissue for altered expression of proteins that regulate growth. Richard Harland, Professor, Genetics & Development, and Chair, MCB Generation of mutants and analysis. The focus of the lab is to understand development; that is, the molecular mechanisms that carefully orchestrate how a single cell (the egg) forms into an adult animal with a multitude of functioning organs. To this end, we are interested in developing the frog, Xenopus tropicalis, into a model genetic system for studying vertebrate development. The closely related frog, Xenopus laevis, has yielded many insights about development but is not amenable to genetic analysis. Therefore we have begun developing methods to generate mutants and analyze loss of gene function and its effects on development of the embryo. There are two avenues of research available for undergraduates: In order to produce mutants, we are currently developing methods to mutagenize animals. We are also developing a whole mount in situ hybridization protocol for detecting gene expression to help detect changes that would indicate gene mutation. Finally once mutants are identified, we will study them to determine the mutated gene and its effects on development. This project will teach a variety of methods in transcript detection and phenotype analysis and interpretation. Michael Levine, Professor, Genetics & Development, MCB; Co-Director, Center for Integrative Biology 1) Evolutionary diversification of dorsal-ventral patterning mechanisms among divergent insects, including honeybees and mosquitoes. Particular efforts could focus on the basis for an expanded midline in the ventral nerve cord of honeybees, and the subdivision of the dorsal ectoderm into distinct amnion and serosa lineages in mosquitoes. 2) Computational methods to determine the basis for complex patterns of gene expression in the early Drosophila embryo. Simple site-occupancy models accurately predict “type 2” expression patterns of rho and vein (EGF signaling molecules) in ventral regions of the neurogenic ectoderm in response to intermediate levels of the Dorsal gradient. It would be interesting to apply these methods to additional processes such as segmentation. 3) Elucidation of the genomic regulatory network underlying gastrulation in Drosophila. The combination of enhancer analysis and genetic studies permit the determination of functional inter-connections among the regulatory genes engaged in gastrulation. The preceding studies will teach students basic methods and concepts in gene regulation, evolutionary biology, and computational biology. David Lindberg, Professor and Chair, IB Shell ontogeny of marine gastropod molluscs. Different rock types (metamorphic, sedimentary, volcanic) weather differently and create different topologies for the organisms that live on them. This topology is reflected in the shell aperture where the snail attaches to the rock. We are currently digitizing shell apertures of snails from different rock types and using geometric morphometrics to quantify the degree of plasticity present in different species. This work will determine if ontogenetic constraints play a role in limiting the distribution of these snails, and whether these constrains are associated with specific size classes. Students participating in this project would be expected to master digital photography, computer-assisted image analysis, and data manipulation and analysis using computer programs. Previous exposure to multivariate statistics would be desirable. Students will learn modern digitization and analytical procedures for the quantification of morphology and will test hypotheses of ontogenetic constraints. Nipam H. Patel, Professor Genetics & Development, MCB and IB Evolution of gene regulation. The goal of this project is to use bioinformatic and developmental approaches to understand the mechanisms of evolution. The student will use bioinformatic tools to investigate evolutionary changes in Hox genes within the arthropods, and experimentally test findings through in situ and antibody staining and the construction of transgenic Drosophila and crustaceans. The student will be exposed to many of the core principles and methodologies of both developmental biology and evolutionary biology, and exposure to both model and non-model animal systems. David A. Weisblat, Professor, Cell & Developmental Biology, MCB, P.I. Cell lineage and cell fate in leech embryos. Small leeches of the species Helobdella (phylum Annelida) are well-suited for studies of embryonic development because their embryos are relatively large, hardy, and consist of individually identifiable cells. Thus, the Helobdella embryo is amenable to a variety of cellular and molecular techniques for elucidating developmental mechanisms. Studies of leech development are of particular interest because they contribute to understanding the super-phylum Lophotrochozoa, a diverse, yet understudied group of animals (annelids, molluscs, flatworms and others) that are evolutionarily distant from more commonly used models such as vertebrates (Deuterostomia) and arthropods (Ecdysozoa). The specific project to be undertaken will be determined according to the student's interests and the state of work in the laboratory. The student will have the opportunity to earn techniques for microinjection, molecular biology, fluorescence microscopy and image processing, plus concepts of lineage tracing and cell fate mapping. Evolutionary Biology George Bentley, Assistant Professor, IB. Relationships Between Reproductive Neuropeptides; Reproductive Physiology & Behavior. My laboratory investigates the interactions of the environment with reproductive physiology & behavior in vertebrate animals. At present we have projects running on a variety of organisms: amphibians, reptiles, birds and mammals. Comparative studies allow us to investigate the evolution of the structure and function of reproductive neuropeptides. In addition, we are able to understand the evolution of their interactions with other hormones that influence reproduction, secondary sexual characteristics and associated behaviors. Students are involved in the whole spectrum of the research, ranging from fieldwork, behavioral observations, blood and tissue sampling to immunohistochemistry and cell and molecular biology techniques such as RT-PCR, in situ hybridization and cell culture. Importantly, previous undergraduates in my laboratory have gone to international scientific meetings and have been authors on peer-reviewed publications in international journals. Rachel Brem, Assistant Professor, Genetics, Genomics & Development, MCB Characterizing noncoding RNAs of unknown function. Recent work in a range of organisms has reported the widespread transcription of genomic regions which do not code for any known protein or functional RNA. Some of this transcription may be the result of nonspecific activity of RNA polymerases. However, many unannotated transcripts are likely to represent messenger RNAs of short proteins or noncoding functional species, including miRNAs and other regulatory RNAs. In previous experiments we have used linkage mapping methods, which harness the natural genetic variation between yeast strains, to find novel regulators of mRNAs. We now wish to apply this approach to noncoding RNAs in yeast. Our goal is to uncover regulators that are responsible for expression differences of these RNAs between strains, and to use such a mapped regulator as the first clue to function of each transcript. An REU student interested in this project will conduct high-throughput transcriptional profiling of genetically diverse yeast strains using tiling microarrays and short-read sequencing; extract, from this whole-transcriptome data, observations of noncoding R. Tyrone B. Hayes, Professor, IB, Co-P.I. Evolutionary Developmental Endocrinology and Endocrine-Disrupting Pesticides in Amphibians, Research in my laboratory focuses on the role of hormones in developmental responses to environmental change in amphibians. Through comparative studies across populations and species, my laboratory seeks to also understand the evolution of mechanisms underlying these responses in amphibians. My work is integrative and has both a laboratory and field component. Fieldwork is conducted throughout the US and east Africa. In particular, I am interested in sexual differentiation and metamorphosis. Most recently, my laboratory has focused on the effects of pesticide on amphibian development. Studies examine effects on metamorphosis, growth, sex differentiation and immune function. Radioimmunoassay, histochemical techniques, and RT-PCR are used to monitor tissue level and cellular changes in hormone synthesis and activity in animals exposed to pesticide mixtures in both the laboratory and in animals exposed in the wild. Undergraduate students are involved in every aspect of the work, including planning, collecting in the wild, rearing and exposing animals in the laboratory, laboratory and statistical analyses, and writing paper for publication/ developing presentations. John Huelsenbeck Professor, IB. Daniela Kaufer Assistant Professor, IB. Stress-induced Silencing of Adult Neuronal Precursors: Identifying Culprits and Buffering Neural Stem Cells What are the environmental and internal cues that control the proliferation and fate choices of stem cells in the adult hippocamus? What role does gene expression have in the translation of those cues that affect the stem cell? What is the functional relevance of stress-induced modulation of adult hippocampal neurogenesis? Using gene delivery methods, Our lab is attempting to answer these questions by investigating the effects of stress and steroid hormones on hippocampal neural stem cells.Specifically, in this project we aim to elucidate the factors which affect the long-term replicative activity and differentiation profile of neural progenitor cells residing in the adult hippocampus using isolated adult hippocampal precursor cells. This will be done using a broad array of molecular/cellular techniques: gene array expression profiling, real time PCR, fluorescent microscopy, laser capture microdissection, immunohistochemistry, and employing gene therapy tools. Nicole King, Asst. Professor, Genetics & Development, MCB and IB Characterization of cytoplasmic bridges in choanoflagellate colonies. Choanoflagellates are unicellular and colony forming eukaryotes that are closely related to animals and used to study animal origins. Cells in the colony-forming choanoflagellate Proterospongia sp. are connected by cytoplasmic bridges. The nature of these bridges and their relationship to animal cell junctions hold important implications for our understanding of animal origins. The student researcher will characterize choanoflagellate cytoplasmic bridges by observing the localization of conserved cytoplasmic proteins and homologs of animal signaling and adhesion proteins. The student will learn techniques for cell culture, Western analysis, fluorescence microscopy, and image processing, as well as concepts of cell biology and evolution. Eileen Lacey, Assoc. Prof. IB. My research program explores the evolution of behavioral diversity among vertebrates, with emphasis on studies of mammals. Specifically, by combining field studies of behavior, ecology, and demography with molecular genetic analyses of kinship and population structure, I seek to identify the causes and consequences of variation in mammalian social behavior. Although I am broadly interested in social behavior and sponsor students working on a variety of vertebrate taxa, my current research focuses on studies of subterranean rodents from Argentina and Chile.
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