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Faculty Laboratories Available for Undergraduate Research Neurobiology & Physiology Ravi Allada (2121 Pancoe) Why do we need to sleep? Why do we wake up in the morning and go to sleep at night? Our research is focused on the daily regulation of sleep behavior using the fruit fly Drosophila and incorporates a variety of approaches including biochemistry, molecular biology, genetics, cell culture, electrophysiology, anatomy, and behavior. Fly genetics has uncovered the molecular logic of circadian clocks that drive our daily rhythms of sleep and wake. They consist of clock proteins that feed back and control their own transcription. Remarkably, highly conserved clocks exist in humans. We are interested in how these molecular networks develop. How does phosphorylation set the speed of the clock? How do these feedback loops influence neuronal activity and output? Astonishingly, fruit flies exhibit periods of inactivity with many of the cardinal features of mammalian sleep, including homeostatic control and similar responses to drugs such as caffeine. We have identified a fly sleep center in a region of the brain also important in long-term memory known as the mushroom bodies (MB). We are interested in understanding how the circadian clock and sleep loss influence the MB, how the MB influence sleep, and what are the links between sleep and learning? Studies in the fly raise the possibility of understanding the elusive function of sleep at the molecular level. Thomas Bozza (2119 Pancoe) My lab uses the olfactory system as a model to understand how genetically-defined neuronal circuits develop, and how these circuits contribute to the representation of sensory information in the brain. The olfactory system mediates the sense of smell. In many animals, olfaction is critical for food location, predator avoidance, individual recognition, as well as social and sexual behaviors that are crucial for the survival of the species. As a model, the olfactory system provides powerful genetic tools to address fundamental questions in neurobiology. The lab is currently studying how odorant receptor genes influence the organization of inputs to the olfactory bulb of the brain, and how this organization contributes to the processing of chemical information. To do this, we use a variety of methods including mouse molecular genetics, optical imaging, and electrophysiology David Ferster (2139 Cook) The mammalian visual cortex performs a remarkable transformation of the information it receives from the eye. Neurons in the cortex are sensitive to the orientation, motion, depth and size of objects in ways that the eye is not, which means the cortex extracts this information from the nonspecific input it receives from the eye. We are studying the neuronal mechanisms by which this cortex performs this transformation. Neuronal connections are traced within the cortex and their functions observed during normal vision by recording intracellularly from neurons in vivo using a patch recording method developed in the lab. Our recent studies have focused on the manner in which excitatory and inhibitory inputs interact, the mechanisms of oscillatory firing and the origin of orientation and direction selectivity in cortical cells. Jon Levine (Hogan 2-120) My research interests are generally in the area of neuroendocrinology, which is the study of the regulation of hormone secretions by the brain, and the regulation of brain function by hormones. Our projects include studies of neurons that produce the 1 Faculty Laboratories Available for Undergraduate Research neurohormone gonadotropin-releasing hormone (GnRH). Neurosecretion of GnRH mediates the control of reproduction hormone secretions and fertility in both males and females, and we are trying to understand how factors such as diet, season, stress, and age can alter fertility by regulating gene expression and electrophysiological activity in GnRH neurons. Many of our studies are also focused on the effects of steroid hormones - estrogen and progesterone in females, and testosterone in males - regulate reproductive behaviors, feeding, aggression, and parental responsiveness. To study the molecular and cellular pathways by which these hormones alter these motivated behaviors, we use a variety of physiological and molecular approaches in mice bearing null mutations of receptors or signaling molecules, and in "gene knock-in" animals which express mutated receptors that selectively activate certain signaling pathways. Our research is ultimately aimed towards attaining a better understanding of certain forms of infertility, normal and aberrant hormone-sensitive behaviors, and the effects of sex hormones on food intake and energy homeostasis. Mark Segraves (2137 Cook) The long-term goal of my laboratory is to understand the neural basis of eye movement planning, with a focus upon neuronal processing taking place within the cerebral cortex and midbrain. These are higher brain centers involved in planning for movement. Both humans and monkeys make series of rapid eye movements called saccades as they look at an image or visual scene. It’s reasonable to assume that both human and monkey plan ahead for several eye movements while viewing images and scenes but there is very little empirical evidence to support this hypothesis. We would like to investigate the behavioral and neural basis of this process in rhesus monkeys, and are approaching this by monitoring neuron activity while monkeys make series of eye movements with conditions emulating the search of a natural environment. Fred Turek (2129 Cook) Research in the Turek laboratory is focused on the study of sleep and circadian rhythms, with special interest in identifying genes that regulate sleep and circadian rhythms. Ongoing work on sleep and circadian rhythms includes an investigation of: (1) the neurochemical, molecular, and cellular events involved in the entrainment, generation and expression of circadian rhythms arising from a central biological clock located in the suprachiasmatic nucleus (SCN) of the hypothalamus, (2) the genetics of the circadian clock system and the molecular genetic mechanisms underlying the sleep-wake cycle, (3) the feedback effects of the sleep-wake cycle on the circadian clock regulating the timing of that cycle, (4) the effects of advanced age on the expression of behavioral and endocrine rhythms, and on the expression of circadian clock genes, 5) the links between sleep, circadian rhythms and energy metabolism and, (6) the role of melatonin in modulating sleep and circadian rhythms. In addition to our work on rodents, we have established extensive collaborations with clinical researchers. Studies in humans are aimed at shifting the human clock in an attempt to alleviate mental and physical problems that are associated with disorders in circadian time keeping, particularly in the elderly and in shift-workers. In addition, we are using both pharmacological and non-pharmacological approaches to determine if we can reverse the effects of aging on the circadian clock system in both rodents and humans. Our sleep, circadian and metabolic studies are focused on how disruption in these interactions can lead to obesity, diabetes and CVD. 2 Faculty Laboratories Available for Undergraduate Research Nelson Spruston (2409 Pancoe) The Spruston lab studies the hippocampus, a region of the brain involved in learning and memory. Our interest lies in understanding the properties of the various types of cells and their functional properties and specializations that may underlie the cellular basis of memory. Undergraduates typically participate in studies directed at understanding the detailed structure or distribution of particular classes of neurons in the hippocampus. These studies involve light and/or electron microscopy as well as immunocytochemical studies. Catherine Woolley Research in the Woolley laboratory focuses on understanding how steroid hormones influence the structure and function of brain circuits to alter behavior or induce pathology. Currently, we are working on two NIH-funded projects. One is about estrogen-induced changes in susceptibility to and severity of seizures related to epilepsy, and focuses on the hippocampus. The other is about sex differences in drug addiction, and focuses on the nucleus accumbens. Each project uses a multidisciplinary approach combining electrophysiology, light and electron microscopic imaging, biochemistry, and behavior. Biochemistry, Molecular Biology and Cell Biology Rich Carthew (3111 Pancoe) The cells in our bodies have specialized tasks, but must also fit together seamlessly in tissues, adopting specific shapes to function properly. Our lab has discovered that complex and beautiful tissue geometries can be explained by a fundamental principle of physics. The observed shapes are accurately modeled by simply letting the tissue find the configuration of least total energy. The major players in this process are the elastic "stretchiness" of individual cells and the adhesive "stickiness" between cells. In this manner, quantitative analysis of intricate tissue patterns is possible. Moreover, applying this principle to tissue engineering could advance regenerative medicine. Erv Goldberg (Hogan 4-100) The Goldberg lab is interested in male reproduction, particularly in how sperm are made and attain the ability to fertilize eggs. We do this work mainly with male mice and study the proteins that appear during the process of spermatogenesis, especially the ones that are unique to the testis. Undergraduates in my laboratory learn how to purify proteins, mostly using recombinant technology, and how to study their function either as interactors with other proteins of the testis or as enzymes involved in energy metabolism for sperm motility. Biochemical and molecular procedures are taught in the lab. The results obtained from our studies may have implications for developing male contraceptives or for curing male infertility. Jon Widom (4133 Cook) Eukaryotic genomic DNA is wrapped into a repeating array of nucleosomes, which occlude their wrapped DNA from interacting with many other gene regulatory proteins. We have discovered that genomes care where along the DNA these nucleosomes are located -- that is, genomes care which stretches of the DNA are wrapped in nucleosomes, and which 3 Faculty Laboratories Available for Undergraduate Research are not. We showed further that genomes manifest this care by encoding an additional layer of genetic information, superimposed on top of the regulatory and coding information that were previously understood. We now have a good ability to read this genomic code for nucleosome positioning, and to predict the in vivo locations of most nucleosomes. Now we seek to understand the molecular basis of this encoding. We believe that it has to do with the sequence-dependent mechanics of DNA itself. DNA in nucleosomes is exceptionally sharply bent; sequences that bend especially easily will therefore be referred by nucleosomes over sequences that bend less easily. A new project in the lab therefore seeks to directly measure dynamic mechanical properties of DNA, such as its flexibility, from static molecular images such as from atomic force microscopy and electron microscopy. Our plan is to construct defined DNAs with sequences of special interest, image these by AFM or EM, and the apply quantitative image analysis to extract desired the dynamic mechanical properties. This work combined molecular biology experimental methods, nanoscale imaging, and quantitative (computer-based) image analysis, and has the potential to revolutionize our understanding of the relationship between DNA sequence and DNA function. Jason Brickner (3105 Pancoe) The current research in the Brickner lab centers on the importance of space and time in cell biology. Specifically, we are studying how the nucleus is spatially organized and how this spatial organization reflects the history of the cell. It has been recognized for more than one hundred years that DNA within the nucleus is spatially organized. The localization of a gene often reflects its expression. Historically, the nuclear periphery was thought to be the place to which silenced regions of the genome are targeted. As a postdoctoral fellow, professor Brickner discovered that certain genes relocalize from the nucleoplasm to the periphery of the nucleus when they are activated in the yeast Saccharomyces cerevisiae. It is now clear from the work of many labs that a large number of genes exhibit similar behavior. The lab seeks to understand how gene localization is controlled and the functional significance of localization in regulating transcription. Kelly Mayo (Hogan 4-112) Our laboratory investigates cell signaling and gene expression in the mammalian reproductive axis. Our research program seeks to understand how hormones secreted from the pituitary gland (FSH and LH) act on the ovary to bring about the changes in cell proliferation, cell differentiation and gene expression that will result in ovulation and luteinization of the ovarian follicle during each reproductive cycle. We use the genes encoding the hormones inhibin and activin, which are produced in the ovary and act on the pituitary gland to regulate reproductive hormone secretion, as a model system to address these questions. We are presently focused on two major research directions. We are investigating the dynamic regulation of inhibin expression during the reproductive cycle, and are exploring the roles of cAMP-responsive transcription factors (CREB and ICER) as well as the related orphan nuclear receptors steroidogenic factor-1 (SF-1) and liver receptor homologue-1 (LRH-1), in this process. We are also investigating developmental pathways in the ovary involved in the initial formation and growth of ovarian follicles, and are attempting to understand how inhibin and activin regulate normal follicle development and how their mis-expression might contribute to the formation of abnormal follicles. These studies also investigate estrogen and Notch signaling in the early ovary, and examine ways in which these pathways intersect with activin signaling. Our research focuses on molecular mechanism 4 Faculty Laboratories Available for Undergraduate Research regulating normal reproductive function, but is substantially informed by, and relevant to, reproductive disorders that impact fertility or result in infertility. Ishwar Radhakrishnan (4135 Cook) The Radhakrishnan lab is interested in understanding how eukaryotic gene transcription is regulated at the molecular level. A variety of projects are in progress that seek to clarify how transcription factors (i) recognize their DNA targets, (ii) set and interpret the histone code, and (iii) collaborate with other factors to accomplish goals (i) and (ii). A variety of biochemical, bioinformatics and biophysical approaches are employed for these studies. Andreas Matouschek (4105 Pancoe) Our goal is to understand a complex cell biological process in the detail at which a chemist understands an enzyme. We hope that a detailed understanding of this type would lead to insights in the biology of this process that would not have been obtained otherwise. We are particularly interested in processes in the cell during which proteins have to loose their structure and unfold, and most recently, we have focused on protein degradation by the proteasome. The proteasome is the major protease in the cytosol and nucleus of eukaryotic cells and controls the concentrations of hundreds of regulatory proteins. It also removes misfolded and damaged proteins from cells and produces some of the peptides that are displayed on cell surfaces as part of the immune response. The proteasome itself is a large protein machine, almost the size of the ribosome. Once it has recognized a substrate, it unfolds the latter and, powered by ATP, runs along the substrate's polypeptide chain, degrading it into small peptides. There are two basic properties of the proteasome what we have investigated: first, the proteasome is not expected to have any preferences for the amino acid sequence of its substrates, because it any protein may end up damaged in the cell and therefore in need of being disposed of; second, one would expect the proteasome to degrade its substrates always completely into small pieces and not to produce larger fragments because these could and would have unwanted biological activities. However, our studies have shown that there appear to be important exceptions to both of these rules. We find that the proteasome has quite pronounced sequence preferences and we are no exploring how these preferences can protect some regulatory proteins from destruction but, unfortunately, also may allow some dangerous proteins to escape detoxification and lead to disease such as in Huntington's Disease. We also found a signal in some proteasome substrates that protects the part of the polypeptide chain behind the signal from degradation. We think that this signal allows the proteasome to fulfill a new role in the cell as a processing enzyme and that this processing is an important part of some signaling pathways. A project in our lab would involve protein engineering, biochemical assays, and cell culture work. Carole LaBonne (3411 Pancoe) The LaBonne laboratory works on the development of the neural crest, a stem cell population that makes central contributions to the vertebrate body plan and has important links to cancer. Investigating the role that specific regulatory factors play in neural crest formation is key to understanding early vertebrate development and also lends important insights into tumorigenesis. Neural crest cells undergo an epithelial-mesenchymal transition (EMT) and migrates to distant regions of the embryo where they give rise to a diverse array of derivatives. The mechanisms underlying the acquisition of migratory and invasive 5 Faculty Laboratories Available for Undergraduate Research characteristics by neural crest cells have been co-opted by tumor cells, allowing them to metastasize to distant site in the body and form secondary tumors. Key transcription factors that regulate EMT in neural crest cells, including Snail, Slug, and Twist, also regulate tumor cell metastasis and are proving to be valuable prognostic indicators for metastatic tumors. Research projects in the LaBonne lab will center on using Xenopus and zebrafish embryos, as well as tumor cell lines, to investigate how specific proteins contribute to this process. Thomas Meade (Tech L110) Our lab’s research interests are focused in the area of the chemistry of life sciences with an emphasis on coordination chemistry, bioinorganic chemistry, biological imaging and the development of electronic biosensors. The specific topics of research and subgroups of the lab include: BIOLOGICAL MOLECULAR IMAGING: Design and synthesis of spectroscopic and magnetic probes that incorporate novel functionality for magnetic resonance and fluorescence in vivo microscopic imaging of biological systems with particular emphasis on nerve patterning, regulation of cell lineage, gene expression and DNA transfection. WEAK INTERACTIONS IN LIGAND-RECEPTOR BINDING: Using transition metal probes to study long-range electronic coupling through stacked ¿-unsaturated systems, proteins and the development of electronic DNA and protein biosensors. METAL COMPLEXES AS ENZYME INHIBITORS: Investigate the interaction of smallmolecule transition metal complexes as enzyme inhibitors for the development of therapeutic antitumor and antiviral drugs. Erik Sontheimer (3137 Cook) The Sontheimer Lab studies the roles of RNA molecules during gene expression, with an emphasis on eukaryotic organisms. The primary focus is on the biochemical mechanisms of RNA silencing pathways such as RNA interference (RNAi), in which small RNA molecules direct the silencing of specific genes. We also study the biological roles and molecular mechanisms of other noncoding RNAs such as microRNAs and natural antisense RNAs. Andrew Dudley (1411 Pancoe) The evolution of higher organisms parallels the formation of increasingly complex relationships between individual tissues. For example, the intricate motor skills of primates depends on precise arrangement of dozens of tendons and muscles on a multi-component articulated limb skeleton. The overall objective of our research is to define the molecular and cellular mechanisms that determine tissue architecture with the goal of developing novel approaches to enhance tissue regeneration. Our current studies use the chick and the mouse limb as model systems for the developing skeleton. In particular, we are elucidating how cell polarity regulates chondrocyte organization and thus determines the unique shapes and growth properties of individual skeletal elements. Alec Wang (1405 Pancoe) The ultimate goal of stem cell research is to repair genetic defects in a patient 6 Faculty Laboratories Available for Undergraduate Research genome, reprogram the patient cells into tissue-specific cells, enroute stem cells, and transplant to repair the damaged tissue. To achieve this goal, reprogramming somatic cells is one of the key steps. To reprogram somatic cells into stem cells, one must understand what genes are essential for stem cells. Our research focuses on identifying novel genes essential for the growth of embryonic stem cells. We have discovered a new family of proteins implicated in microRNA pathway plays an essential role to maintain the survival and growth of embryonic stem cells. We are currently examining a new way to reprogram somatic cells by microRNAs. Alfonso Mondragon (4131 Cook) We are interested in the structure and function of proteins and nucleic acids. Two areas of particular interest to us are: 1) nucleic acids and proteins that interact and modify them, 2) flexibility and conformational changes in proteins. An example of our work on the first subject is our study of the mechanism of type IA DNA topoisomerases. We have solved the structure of both E. coli DNA topoisomerase I and III and their complexes with nucleic acids. These structures have allowed us to propose a detailed mechanism of action for this type of enzymes. We are also interested in the structure of large nucleic acids. We are currently studying the structure of the RNA component of RNase P, a large catalytic RNA molecule. The second area is exemplified by our studies of spectrin flexibility. We solved four structures of tandem repeats of spectrin and used these structures to propose atomic mechanisms to explain spectrin flexibility. Rick Morimoto (3129 Cook) Aging and stress, stress and aging — a pair of ominous human conditions that affect quality of life. When events go awry, molecular events take place that, over time, can lead to or enhance the risk of neurodegenerative disease. At the root of problem is a fundamental process common to all cells, protein folding. When proteins misbehave and misfold, they can adopt altered states that cause diseases of protein conformation including the neurodegenerative diseases Huntington's disease, Amyotrophic Lateral Sclerosis, Alzheimer's disease, Parkinson's disease, and Creutzfeld-Jacob. For each, a hallmark of the disease is the appearance of misfolded and mutant proteins (Huntingtin, superoxide dismutase, amyloid b peptide, a-synuclein) and associated toxicity. How these proteotoxic species form, the processes that determine their persistence or clearance, and the molecular basis of their toxicity are critical to understanding the disease mechanism. We study how misfolded proteins cause cell stress and interfere with cellular function, the identification and characterization of cellular machineries in protein homeostasis that recognize and detoxify misfolded proteins, the basis of cell-type specific neurotoxicity, and the identification of genes that regulate lifespan as a modulators of these events. The identification of the chaperome network that determines protein quality control thus forms the basis for a new class of therapeutics for neurodegenerative diseases of aging. Robert Holmgren (3125 Cook) The Holmgren lab studies signaling between cells. We are particularly interested in the Hedgehog (Hh) pathway, which is conserved throughout most of the animal kingdom. In humans, Hh is responsible for patterning the neural tube, appendages, and many organs. Our research is focused on how Hh signaling leads to the translocation of the Ci/GLI transcription factors into the nucleus and the subsequent activation of target genes. We 7 Faculty Laboratories Available for Undergraduate Research study these questions in mammalian tissue culture and fruit flies using a variety of genetic, molecular and cell biological approaches. Eric Weiss (3413 Pancoe) How does one cell become different from another? The process of cell fate determination can be driven during cell division by asymmetric segregation of molecules or structures that influence gene expression. Such segregation is intimately tied to the underlying architecture of the cell and the timing of mitosis. We use the budding yeast S. cerevisiae to understand how fundamental mechanisms of cell differentiation, the control of cell morphology, and cell cycle regulation are coordinated. Our work largely centers on protein kinase signaling cascades, and one of our key aims is to map the flow of information through intracellular networks as comprehensively as possible. Heather Pinkett (4129 Cook) From bacteria to mammals, ATP-Binding Cassette (ABC) transporters are prevalent everywhere there are cells. ABC transporters work as membrane bound molecular pumps to import or export a broad spectrum of substrates, including proteins, sugars and toxins. They use the binding and hydrolysis of ATP to power the transport substrates across cellular membranes. To date, more than 50 human diseases are linked to defective transporters, including cystic fibrosis. In the presence of ABC transporter multidrug resistance protein 1 (MDR1), tumor cells are resistant to chemotoxic drugs, a particular limitation to cancer chemotherapy. Deciphering the mechanism of transport, substrate specificity and the role of ATP in substrate translocation is of great interest in the field. The Pinkett lab is interested in understanding how this super family of proteins may use a similar mechanism to transport select substrates into or out of the cell and the role mutations play in reducing its ability to function as a transporter. Greg Beitel (1407 Pancoe) Claudin-family proteins are small four trans-membrane domain proteins that are integral parts of the junctional complexes that prevent fluid and ion passage between cells. These “paracellular barriers” are important in epithelial tissues to separate internal organs from the outside environment (e.g. prevent acid stomach contents from leaking into the blood stream) and in endothelial cells and glia to create the blood/brain barrier that protects the nervous system from pathogens and potentially dangerous chemicals. Although claudins have been shown to play central roles in the barrier, the functions of the different parts of claudin molecules are poorly understood. In Drosophila, two related claudin molecules, Sinuous and Megatrachea, are both required to for barrier junction formation. That they are both required indicates that they have distinct functions. To identify the parts of these proteins that confer the distinct functions, we are making a series of chimeras (domain swaps) between the two proteins. Using transgenic animals, genetic crosses and immunohistochemical assays, we will investigate the in vivo function of the chimeric proteins. Once regions that harbor specific functions have been identified, we would work to identify proteins that interact with those regions. Amy Rosenzweig (4137 Cook) The goal of our research program is to understand metalloprotein function on the molecular level by using X-ray crystallographic, biophysical, and biochemical techniques. 8 Faculty Laboratories Available for Undergraduate Research Projects in the laboratory are divided into two areas, metalloenzymes and metal trafficking proteins, with an increasing focus on structural characterization of integral membrane proteins. We recently determined the molecular structure of Nature’s predominant methane oxidation catalyst, a metalloenzyme called particulate methane monooxygenase (pMMO). pMMO converts methane, the most inert hydrocarbon, to methanol. We have also determined structures of metallochaperones involved in copper delivery to Cu +-ATPases and to cytochrome c oxidase. Mutations in Cu+-ATPases, which are integral membrane proteins that couple the energy of ATP hydrolysis to Cu+ translocation across membranes, are linked to Wilson disease and Menkes syndrome. Other Departments Joe Bass (4405 Pancoe) The major focus of research in the Bass laboratory is on the molecular links between neural circuits coordinating sleep, wakefulness and feeding behavior, with systems important in peripheral fuel utilization, including the insulin-signaling pathway. Two overarching themes in our research are: (1) Transcriptional and posttranslational interactions between circadian and metabolic gene networks in the development of diabetes and obesity: We discovered that mutation of the gene encoding the transcription factor CLOCK, present within both brain and in peripheral metabolic tissues, leads to altered sleep, feeding activity, obesity and diabetes (Science 2005). These studies prompted us to search for targets of the Clock gene network within appetite centers of the brain and within peripheral tissues involved in lipid and carbohydrate utilization. Our work led to the surprising observation that mutation of the Clock gene disrupts hypothalamic expression of the wakefulness peptide hypocretin/orexin and appetite-suppressing neuropeptide melanocyte-stimulating hormone. Projects in the laboratory now exploit both genetic and biochemical methods to pinpoint the cell and molecular basis for co-regulation of circadian, sleep and metabolic pathways within specific cells of hypothalamus, and peripheral metabolic tissues. (2) Genetic and genomic analysis of glucose metabolism and insulin resistance: We have developed genetic and genomic tools to evaluate targets involved in the regulation of body weight, glucose and lipid metabolism in vertebrates. We have used “reverse” gene targeting to create new diabetes “knock-in” mice in which human mutations have been introduced into the mouse genome. The new humanized diabetic mice that we have generated reconstitute the human disease but also lead to profound defects in the regulation of sleep, activity and feeding. These studies are conducted in parallel with analyses of factors regulating cell and molecular control of insulin receptor signaling within brain and peripheral metabolic tissues including liver, pancreas, fat and muscle. Gene knockin and cell-based platforms provide new approaches to correlating genotype with phenotype in human insulin resistance syndromes. Understanding the pathways that link circadian activity, sleep, feeding and metabolic homeostasis, and delineating the impact of changes in each parameter on the whole organism, will hopefully bring us one step closer to a unified “systems” map of metabolic disease. Kurt Horvath (4401 Pancoe) My lab studies mammalian antiviral responses and the strategies that some viruses have evolved to evade them. Diverse projects are underway, exploring the molecular basis for virus detection, the cytokine signal transduction apparatus leading to virus-induced host gene expression, and the biological activities of the antiviral effects of the protein 9 Faculty Laboratories Available for Undergraduate Research products. In parallel, the unique capacity of RNA viruses to disengage these host immune responses is being dissected at the molecular and biochemical level. Hans-Georg Simon (Childrens Hospital; [email protected]) Building and re-building of limbs and hearts. The Simon Laboratory has identified regulatory genes that play key roles in limb development in virtually all vertebrates, including humans. Surprisingly, these genes are also critical for the shaping of the heart during embryogenesis and when mutated in humans, they lead to birth defects of the arms and heart. Using zebrafish, chicken, and mouse models, the lab tries to gain a deeper understanding of common genetic pathways in limb and heart development and disease. In addition to these developmental studies, the lab is interested in discovering the genes that are involved in regenerative processes. As models for these investigations, zebrafish and newts are employed, which can regenerate limbs and heart ventricles throughout their life times. The identification of genetic pathways that are operational in these regenerating species but not in mammals, will provide new insights how to restore regenerative abilities in non-regenerating species including humans. 10