Grant #P20RR016454 
 funded by NIH  NCRR

University of Idaho Prospective Mentors-2008

Name: Institute: Department: Email: Website:	Matthew Anway University of Idaho Biological Sciences manway@uidaho.edu
Research: The research in my laboratory examines the link between sublethal environmental toxicants and transgenerational fetal basis of adult disease. We investigate the affects of environmental dichlorophenyl dicarboximide fungicides( i.e. vinclozolin, procymidone and iprodione) on the epigenetic programming of the germ line during embryonic development and how this programming affects adult disease states. Specifically my interest is in how adult male diseases such as prostate and testis disease are induced following such exposures to a pregnant female. We have shown that vinclozolin can induce infertility and prostate hyperplasia in male rats exposed during embryonic development and that these diseases can then be transmitted to future generations through the exposed male germ line(sperm) DNA. We are investigated the casual mechanism and underlining genes responsible for the disease induction and well as the heritable nature of the phenotype. Since embryonic exposure to vinclozolin induces an epigenetic transgenerational effect diseases in the male reproductive tract, we are interested in investigating if other members of the dichlorophenyl dicarboximide fungicides are able to induce reduced spermatogenesis and prostate hyperplasia.     Summer Project: The INBRE fellow working in my lab will investigate changes in gene and protein expression via RT-PCR and western blot analyses, respectively. One of the potential problems in the prostate is localized regions of hyperplasia. This summer INBRE student will be assigned to monitor the induction of cycle genes associated with hyperplasia, such as cyclin D1 and E. The student will follow the gene and protein expression through multiple generations, F1-F3. These studies will also involve RNA isolations, oligo design and testing of PCR conditions. Plus, the INBRE student will be exposed to animal husbandry. If time permits the student will be taught immunolocalization technique to localized protein expression in cross sections of tissues samples.     Name: Institute: Department: Email: Website:   Dr. Gustavo  Arrizabalaga University of Idaho Microbiology Molec. Biology and Biochemistry gustavo@uidaho.edu http://www.ag.uidaho.edu/mmbb/       Research:        Toxoplasma gondii is an obligate intracellular parasite capable of infecting virtually any nucleated cell from a wide range of mammalian and avian species.  Toxoplasma is one of the most widespread and successful protozoan pathogens and is a common parasite in humans where it has become one of the main opportunistic pathogens in AIDS patients.        Some of the most devastating effects of infections by intracellular parasites are a direct consequence of their lytic cycle, which consists of attachment to the host cell, invasion, intracellular replication and egress.  Both invasion and egress by Toxoplasma are essential for infection and survival, involve fluctuation in intracellular [Ca+2], morphological changes and secretion from various organelles.  Egress in particular is an active response to unknown signals and a process fatal to the host cell.  The goal of our lab is to answer the specific questions: “what are the molecular and genetic elements involved in egress?” and “what are the cues telling the parasite to exit its host cell?”  To answer these questions, our lab utilizes a combination of molecular genetics, cell biology and biochemistry.   Summer Project:        Recently, I identified an uncharacterized Sodium Hydrogen Exchanger (TgNHE1) as being involved in egress and Ca2+ homeostasis.  I will continue to characterize this particular ion exchanger by identifying interaction partners and its role in othe calcium dependent processes such as invasion and motility.  A search for other NHE homologues through the Toxoplasma genome database reveals the presence of 3 other NHEs in this parasite.  Given the importance of ion exchange for the life cycle of this parasite, it is important to understand the role of these other NHEs in the lytic cycle of this parasite.  A project to be performed by a summer student would involve cloning one of the unidentified NHEs and studying its function by creating a knock out strain and its intracellular localization by making antibodies against the NHE.  This project would involve molecular biology techniques such as PCR, cloning and Western analysis, as well as cell biology methods such as immunofluorescence assays.     Name: Institute: Department: Email: Website:   Dr. Eric Aston University of Idaho Chemical Engineering aston@uidaho.edu   Research:       My broad research interests include collaborative investigations in chemical and biological sensors, microfluidics, biological applications of nanomaterials, mechanical behavior of nanostructures, synthesis of polymeric, ceramic, metallic and composite nanowires, and imaging and mapping of physical and chemical structure at the microscale and below. Application areas include studies relevant to toxicity of nanomaterials and the mechanisms involved in cellular uptake and cell death FORMTEXT ; chemical modification of biomacromolecules, fibers, cells, and tissues; characterization of bioconjugated structures; fabrication and testing of biosensors with DNA duplexes, bacterial adhesion, protein binding affinity, and others. Most of these projects include multiple faculty members and students working together across departments, colleges, and university campuses. The main function of my laboratories (see website for facilities) is toward characterization of materials and their behavior in systems and devices.  INBRE fellowships will get experience working in more than one laboratory along side other student, staff and faculty investigators in a stimulating multidisciplinary environment. They will also have the opportunity to coauthor research publications.   Summer Project: All potential projects will involve collaboration with one or more other research groups in the biological sciences. The first project is mapping the location of nanomaterials in and around cells, internal cell structures and cellular matrices; this is relevant for cell delivery of drugs or imaging contrast agents as well as fundamental studies of cellular uptake, interactions with nanomaterials, and diagnostic mapping. New optical scanning techniques available at the University of Idaho provide the current state-of-the-art capabilities in fluorescence and Raman (chemical) spectroscopy for high-resolution mapping. These techniques are combined with atomic force microscopy (AFM) and scanning near-field optical microscopy (SNOM) that allow imaging down to the nanometer scale. A second potential project is the characterization of chemically modified collagen microfibrils, using some of the same techniques above. A third project is the testing of biosensor response and optimizing fabrication; these sensors are designed to be quantitative for concentration rather than traditional devices that only detect the presence of a molecular species. Another possible project (related to biosensors and chemical detectors) is a study of electrode wettability and fouling by biomacromolecules; this will involve the synthesis of nanomaterials into a test structure and experiments on the changes of the response behavior with time and exposure to biological entities, like proteins and cells.   Name: Institute: Department: Email: Website:   Dr. Tom Bitterwolf University of Idaho Chemistry Department bitterte@uidaho.edu   Research:      For the last several summers INBRE students have joined my group working on projects directed toward the preparation of metal nitrosyl compounds for use as diabetes drugs. Conceptually the idea of this project is simple. One of the late term consequences of diabetes is loss of circulation in the extremities and skin. Research in the medical community points to a break down in nitrogen oxide signaling between red blood cells and the epithelial cells of the capillaries as a likely culprit in the appearance of these symptoms. Unknown at present is whether the problem centers on difficulties in the release of bound nitrogen oxide by the blood cells, or to changes in the NO receptors in the epithelial cells making them less sensitive to signaling. What is known is that introduction of compounds that boost nitrogen oxide levels in the affected areas does provide at least temporary relief. Our research has been directed toward the synthesis of compounds that will release NO when exposed to low energy light. Because of the large number of ways nitrogen oxide is used in living organisms it is not a good idea to introduce drugs that will generate nitrogen oxide throughout the organism. There are simply too many side reactions that might result from such a medication (Viagra comes to mind as an example of unexpected nitrogen oxide release). The extremities and skin are ideal, however, for activation of a drug by light. In particular we focus on long wavelength, low energy light in the yellow to red portion of the spectrum since these wavelengths easily penetrate 1 cm or more into the body.    Summer Project:       Our research program has centered on the photochemistry of metal nitrogen oxide compounds and we have a good understanding of the underlying chemistry and photophysics of these compounds. Translating this understanding to compounds that might serve as a photopharmaceutical drug, however, involves building compounds that have the correct combination of chemical stability, photochemical sensitivity, and limited toxicity. Our proposed research will follow up on our progress from the last several years and examine iron and cobalt compounds with ligands built from amino acid cyclic dimers. For example, cyclodicysteine is an interesting ligand that brings two SH groups together in an ideal geometry for binding to a metal. These compounds are not trivial to synthesize so some of our work this coming summer will be devoted to what appear (on paper) to be improved routes to cyclodicysteine. The remainder of the work will focus on the synthesis of iron and cobalt nitrosyl compounds closely related to compounds we have previously shown to release NO. While the work presupposes a working knowledge of chemistry it is not necessary for a student to have extensive laboratory experience before the summer.   Name: Institute: Department: Email: Website:   Dr. Eric Brauns University of Idaho Chemistry Department ebrauns@uidaho.edu www.chem.uidaho.edu     Research: The focus of my research is on the study of folding and dynamics of RNA molecules.  RNA is a biopolymer that is found in all living organisms in all kingdoms of life.  It plays a central role in many of the most fundamental biochemical reactions.  In addition to its well known role in transcription and translation, RNA has recently been found to play a key function in the regulation of gene expression and is also linked to numerous diseases.  A common theme in all biochemistry is that structure and function are closely intertwined.  In other words, an RNA molecule must fold into a specific three dimensional structure in order to function properly.  Furthermore, the structure is quite dynamic and undergoes localized fluctuations and small scale conformational changes in response to environmental pressures and molecular demands.  To fully understand RNA function, we must thoroughly investigate its dynamic properties.           My group does this using time resolved infrared (IR) spectroscopy.  The molecular groups in an RNA molecule absorb certain wavelengths of IR light.  The local environment of these molecular groups will affect the amount of light that is absorbed as well as the characteristic wavelength.  As RNA structure evolves, these molecular groups experience a range of local environments that are reflected in their IR absorption characteristics.  Thus, we can use IR spectroscopy to monitor folding and dynamics of an RNA molecule.  We use a short laser pulse to rapidly raise the temperature of a small volume of an RNA sample.  We can achieve temperature "jumps" up to 20 degrees in as short as 10 nanoseconds.  The RNA unfolds in response to the temperature jump.  Using a second laser tuned to a specific IR wavelength, we then "watch" the RNA as it re-folds.  This experiment allows us to study RNA folding and dynamics from nanoseconds to 100s of microseconds.  Summer Project:       Within an RNA molecule there are regions of characteristic structural elements called "motifs".  One of these motifs is known as a tetraloop.  A tetraloop forms when a region of RNA folds back on itself creating a loop of 4 unpaired bases at the point of the fold.  The tetraloop motif is found in all RNA molecules regardless of the type of organism.  Since it is one of the most common of all the possible motifs, a vigorous effort is underway to understand the forces that govern its formation.  To date, most studies have been on relatively slow timescales.  However, tetraloops form quickly and a great deal of information is missed.  The laser induced temperature jump experiment (described above) enables us to study folding on timescales as short as 10 nanoseconds.  A student in my lab this summer would be able to participate in a detailed study involving a series of short oligonucleotides that are known to form stable tetraloops.  This study will begin to address the sequence dependence of the structural dynamics.  Work will begin with a systematic evaluation of the equilibrium IR spectroscopy of the samples.  This will establish a solid foundation upon which time resolved studies will be built.  While the work presupposes a working knowledge of chemistry it is not necessary for a student to have extensive laboratory experience before the summer.     Name: Institute: Department: Email: Website:   Dr.Joseph Cloud University of Idaho Biological Sciences jcloud@uidaho.edu   Research:       My laboratory is concerned with issues involving the reproductive biology of fish. Our two major projects are as follows: The transplantation of cells from sexually immature, sockeye salmon testes into sterile, rainbow trout embryos to produce sockeye oocytes or eggs. The biological questions that are being researched are (a) whether the germinal stem cells of these immature testes can act like primordial germ cells and migrate into the genital ridges, (b) whether male germ cells from sockeye that colonize the developing ovary will develop into eggs, and (c) whether the resultant surrogate will spawn once (like a salmon) or multiple times (like a trout). Current evidence is consistent with the conclusion that sexually mature, male rainbow trout that are exposed to 17α-ethynylestradiol (EE2, the synthetic estrogen in birth control pills; an environmental estrogen) during the time that they are undergoing spermatogenesis will produce aneuploid sperm (sperm with the incorrect chromosome number). The questions that are being examined are (a) when does EE2 have this biological effect and (b) is this effected mediated through an estrogen receptor.    Summer Project:          Transplant fluorescently labeled, salmon testicular cells into female rainbow trout embryos and follow the migration of the cells and the colonization of the genital ridges. The experimental variables will be the ploidy of the recipient (diploid vs. triploid) and the time of transplantation relative to fertilization (age of the embryo) Modify an invitro organ culture system for sexually immature rainbow trout testicular tissue to support spermatogenesis.  The endpoint of this project would be whether the fragment could produce haploid cells as determined by digesting the testicular fragment and measuring ploidy with a flow cytometer). If this objective is met quickly, the next part of the project is to determine if the addition of EE2 to testes undergoing spermatogenesis in culture will result in aneuploid haploid cells.     Name: Institute: Department: Email: Website:   Dr. Doug Cole University of Idaho Microbiology Molec. Biology and Biochemistry  dcole@uidaho.edu www.ag.uidaho.edu/mmbb/p_cole_d.htm Research:           We are studying intraflagellar transport (IFT), a molecular motor-driven motility that is essential for the assembly and function of all eukaryotic cilia and flagella.  Functionally, we have linked IFT in cilia to human polycystic kidney disease.  IFT is also linked to retinal degeneration, cystic fibrosis, male infertility, and most recently, Huntington's disease and Bardet-Beidl Syndrome.  More specifically, we have identified the large protein complexes that are moved in and out of cilia and flagella and we are currently characterizing the individual cargo protein subunits and the motor proteins that move them.  A primary focus of this research is the characterization of protein-protein interactions within these complexes.  These studies are being combined to elucidate the structural architecture of the larger complex.  In short, we use a combination of biochemical and molecular techniques to solve biological problems at the cellular level.  In our laboratory, each student will become an integral member of the team but will do so by working on a unique part of the puzzle.  The ideal candidate will want to learn how to purify, manipulate and characterize both DNA and protein.   More details can be found at our web site www.ag.uidaho.edu/mmbb/p_cole_d.htm   Summer Project:          Fellowship projects depend on the experience and interest of the individual.        Novice fellows would likely work on the expression and purification of a novel protein.  This type of project has been very successful in the past and it allows the student to learn techniques associated with both molecular biology and protein biochemistry.        Students that already have some laboratory experience may have a more advanced project such as analyzing protein structure or testing for protein-protein interactions.  Both of these projects will involve manipulation of DNA and characterization of protein.   Name: Institute: Department: Email: Website:   Dr. Ron Crawford University of Idaho Microbiology Molec. Biology and Biochemistry /EBI crawford@uidaho.edu     Research:   Microbial physiology and genetics; subsurface microbiology; microbiology of extreme and extraterrestrial environments; molecular characterization of microbial communities; biodegradation of hazardous waste and in situ biodegradation; lignocellulose biodegradation; restoration of chemically-contaminated soil and water.    Summer Project:   Characterization of viruses in drinking water: students employ microarray-based techniques to examine nucleic acids extracted form water to identify genes that are signatures for the presence of specific types of viruses. With microarrays it is possible to examine a water sample for thousands of viruses during a single experiment. It also is possible to use these techniques to determine whether water treatment technologies have cleaned water of pathogenic organisms sufficiently for safe re-use of the water, including as drinking water.   Name: Institute: Department: Email: Website:   Dr. Kurt Gustin University of Idaho Microbiology Molec. Biology and Biochemistry kgustin@uidaho.edu http://www.ag.uidaho.edu/mmbb/     Research: Picornaviruses are prevalent human pathogens and cause diseases ranging from the common cold, to jaundice and paralysis. Included in this family are poliovirus, rhinovirus and coxsackievirus. My goals are to understand the host-pathogen interactions that occur during picornavirus infection. During poliovirus and rhinovirus infection a number of host nuclear proteins relocalize from the nucleus to the cytoplasm. Recently, we demonstrated that both poliovirus and rhinovirus infection cause a dramatic inhibition of nuclear import coincident with the cytoplasmic accumulation of host nuclear proteins. We have also shown that two components of the nuclear pore complex (NPC), Nup153 and p62, are degraded during infection, thus providing a potential mechanism to account for the observed inhibition of nuclear import. Inhibition of nuclear import is predicted to result in the cytoplasmic accumulation of a number of nuclear proteins that normally function in RNA biogenesis and transport, activities that an RNA virus replicating in the cytoplasm might find advantageous. Additionally, many anti-viral responses involve the transport of cytoplasmic signaling molecules, such as NF-kappaB and STATs into the nucleus. Inhibition of nuclear import may thus provide an attenuated anti-viral response and lead to a more productive replicative cycle in vivo. Currently, the major focus of the lab is to determine the role that inhibition of nucleo-cytoplasmic trafficking plays in viral replication and pathogenesis and the impact of this inhibition on the host cell. Summer Project: 1. Examine the inhibition of host anti-viral responses that we observe in rhinovirus-infected cells. This project would also involve working closely with a graduate student and would examine the status of components of the anti-viral signaling pathway in infected cells. 2. Characterize the mechanism of silica nanowire-mediated delivery of materials to the inside of cells. Develop silica nanowires as a platform for the delivery of reagents both in vitro and vivo.     Name: Institute: Department: Email: Website:   Dr. Patricia Hartzell University of Idaho Microbiology, Mol. Biol and Biochem hartzell@uidaho.edu       Research:   Myxococcus xanthus is a model bacterium that we use to study motility and multicellular development. Our goal is to understand how a bacterial cell uses two different motors simultaneously to glide over a surface and how these two motors are coordinated when the cell reverses direction. We use genetic tools to identify genes encoding proteins involved in gliding, and molecular and biochemical tools to determine the structure and function of these proteins. Our characterization of MglA, MglB, AglZ, and Agl-Agm proteins has allowed us to generate a new model for the mechanism of gliding. MglA is a Ras-like monomeric GTPase that is essential for A and S gliding. We have shown that MglA interacts with at least three other proteins - AglZ, MasK and MglB. To understand the function of AglZ, MglB and MglA, we generated strains that express fusions of these proteins with the fluorescent tags, Yfp, Gfp, and mCherry. We showed that AglZ-Gfp is arranged in a spiral inside the cell and that AglZ may be the internal cytoskeletal component that makes contact with proteins on the cell surface to generate force. Our results show that MglA-Yfp, which interacts with AglZ, also is arranged inside the cell in a spiral shape in a static, nonmoving cells. In contrast, when the cell moves, some MglA-Yfp is found clustered at the poles of the cell, but a portion of the MglA migrates from front to back. We are testing the hypothesis that GTP hydrolysis by MglA at the pole of the cell initiates the directional polymerization of AglZ, the internal myosin-like part of the force-generating motor. We have shown that MglB regulates MglA. MglB is a member of the LC7/roadblock family of proteins. In eukaryotes, all known members of this family interact with ATPases and GTPases to regulate their activity. We have analyzed a series of MglB mutants that have an altered LC7/roadblock consensus and have also shown that the stoichiometry of MglB and MglA in vivo is critical for motility and development. Summer Project:   Mutations in the mglA gene, which encodes a regulatory GTPase, affect motility and development of Myxococus xanthus. Our work has shown that a tagged form of MglA, called MglA-Yfp (yellow fluorescent protein), is a dynamic protein that migrates through the cell as the cell moves. The INBRE summer student will carry out a detailed examination of a collection of mutants that express altered forms of MglA and exhibit phenotypes that range from nonmotile to fully motile. The goal is to test the hypothesis that mutations in mglA that affect GTP hydrolysis block the ability of MglA to interact with specific cytoskeletal proteins. To test this hypothesis, each mutant will be studied by time-lapse videomicroscopy and the movement of individual cells will be quantified for rate, reversal frequency, and percentage of time in motion. A subset of the mutant mglA alleles will be fused with Yfp and analyzed by fluorescence videomicroscopy to track the dynamic movements of the mutant forms of MglA in vivo. The INBRE student will have hands-on experience with sophisticated microscopes and tracking software. S/he will perform many types of motility and development assays that generate critical data that we can use to better understand the correlation between the genotype and the phenotype of mglA alleles. The INBRE student will be expected to spend time developing three-dimensional models for MglA based on the crystal structure of Ras and mapping the mutations on this model.  Name:  Institute:  Department:  Email:  Website:   Dr. Rod Hill University of Idaho Animal and Veterinary Science rodhill@uidaho.edu http://www.avs.uidaho.edu/faculty/hill.htm Research:   Hormonal control of growth / leptin-insulin interactions.        Our research group is interested in the hormones which affect growth, control the use of energy/substrates/nutrients and the way in which the body grows muscle or deposits fat.  We work with other groups nationally and internationally.  The group this summer will include, a support scientist, two graduate students and two or three undergraduate students.Our focus is on the interaction between the hormones leptin and insulin.  In brief, insulin acts to store energy (in the form of glucose, fatty acids and proteins), and leptin acts to mobilize some of these fuels – especially fatty acids.  There are many newly discovered interactions between leptin and insulin and this is an important and exciting new research field.        This work is at the fundamental level of research and has application in the field of DIABETES RESEARCH.  One hypothesis is that leptin blunts insulin actions in peripheral tissues, leading to peripheral insulin resistance – a major factor in Type II Diabetes.  Our studies utilize cultured muscle cells.  The activation of an intracellular protein called insulin receptor substrate-1 (IRS-1) by insulin and leptin has shown that this is an important messenger, regulated through both axes. Our studies use the latest scanning equipment to identify phosphorylated messenger proteins which interact with IRS-1.  At the level of gene expression we are using gene chip technology and quantitative PCR to confirm and support our observations at the protein level.   Summer Project:        In a recent study of myogenic (muscle cells) in culture, IRS-1 total protein, IRS-1 phosphorylated at serine 307 (pS307-IRS-1) and p70S6 kinase recruitment on IRS-1 in response to insulin (100 nM), leptin (60 nM) or pretreatment with leptin (60 nM, 10 min) followed by insulin (100 nM, time-course, 1, 10, 30 and 120 min) showed for the three protein targets a peak response at 1 min (p < 0.05), which then decreased to baseline values.  Insulin or leptin treatment alone appeared to induce only minor changes (not significant).  The increase in total IRS-1 in response to the sequential treatment, was paralleled by an increase in pS307-IRS-1 phosphorylation which is an accepted mechanism directing IRS-1 to the proteosome degradation pathway.  Furthermore, the synchronous increase in p70S6 kinase recruited to IRS-1 suggests that this may be the serine-threonine kinase which is the major contributor to modulation of IRS-1 degradation following phosphorylation at S307.  Because neither hormone treatment alone resulted in induction of these phenomena observed in the sequential treatment, we speculate that p70S6 kinase may be a linking molecule in the cross-talk of the leptin and insulin signaling pathways.  Student projects this summer will investigate regulation of p70S6 kinase gene expression which accompanies these changes at the protein level.  Quantitative PCR will be used to more precisely define changes in expression of p70S6 kinase and other regulators of this pathway also recently detected using Affimetrix Genome Array.  Novel candidate genes identified by the array technology may be more precisely quantified in these student projects.    Name:  Institute:  Department:  Email:   Dr. Zonglie Hong University of Idaho Microbiology, Molec. Biology, & Biochemistry zhong@uidaho.edu   Research:        My research interest is biochemistry, molecular and cell biology of plants.  In my laboratory, we clone new genes from plants and study their biological functions.  We purify proteins from plants and measure their enzyme activity.  We investigate how the activity and function of these proteins are regulated.  The approaches taken in my laboratory include genetics, biochemistry, cell biology, genomics and proteomics.  Protein kinases are key components of signal transduction pathways in both plants and animals.  Knowledge accumulated from the study of plant USP kinases will help understand how stress signals are perceived and translated into proper responses in animals.        Two projects in my laboratory are currently supported by grants from the National Science Foundation (NSF).  One project is aimed at understanding how a novel protease regulates callose synthase activity during the course of flower development.  When callose synthase activity is not regulated properly, pollen grains become male-sterile.  The other project is focused on how cell division and cytokinesis are regulated at the molecular level.  In addition, we have recently developed a third project that is aimed at elucidating how plant cells perceive various environmental signals.  We are recruiting an undergraduate student to work together with a graduate student on this project.        The research team in my laboratory consists of two postdoctoral fellows, three graduate students, one lab technician, and two undergraduate students.   Summer Project:        Environmental stress is the single most important factor that limits growth and productivity of crops.  The most common stresses include drought, salinity, heat, cold, nutrition shortages, heavy metals, and exposure to UV-light and toxic chemicals.  Unlike animals that can move away from an unfavorable location, plants cannot migrate and have to adjust their cellular metabolism to deal with various stresses.  Plants develop a network of signal transduction pathways to perceive and transduce stress signals.  We have recently identified a protein, referred to as the universal stress protein (USP).  This protein appears to play a pivotal role in the integration of various environmental stress signals.  It is an autophosphorylated protein kinase.  The goal of the summer project is to identify which amino acid residue(s) is phosphorylated, and how this autophosphorylation is regulated under stress conditions.  The undergraduate student will be trained to use a variety of laboratory techniques including gene cloning, protein expression and purification, protein kinase activity assay, mutagenesis and proteomics.  The student will also have an opportunity to interact with an active research group, and gain biomedical research experience through participation.      Name:  Institute:  Department:  Email:  Website: Dr. Patrick Hrdlicka * University of Idaho Chemistry hrdlicka@uidaho.edu http://www.webpages.uidaho.edu/~hrdlicka/index.htm   Research: Research in the Hrdlicka laboratory focuses on the development of designer nucleic acids for applications in medicinal chemistry (e.g., targeting of double-stranded DNA and gene therapy), diagnostics (e.g., detection of single nucleotide mutations), and nanobioscience (e.g., ultrasensitive biosensors, drug delivery carriers). Dr. Hrdlicka has been involved in the development of novel classes of designer nucleic acids, which are based on the LNA-technology (locked nucleic acid) known to increase thermal duplex stability, increase single mismatch discrimination and improve stability of antisense constructs toward enzymatic degradation. These building blocks allow placement of functional entities in nucleic acid constructs with unprecedented levels of positional control, which has allowed us to develop a wide variety of interesting probes. For further info on our research please go to our new lab webpage !!!   Summer Project: You will be able to choose from a range of projects dealing with design, synthesis and/or biophysical characterization of chemically modified nucleotide building blocks for applications in the areas described above. One of the possible projects that you could be working on is:  "Development of dsDNA targeting methodology": We have designed a novel type of nucleic acids that target double stranded DNA very efficiently, and which thereby have the potential to prevent the formation of certain cancer-causing proteins. In this project you would work on the characterization of these probes and/or synthesize new optimized nucleic acids. However, many other projects are available – just contact me for further discussion J  Among the experimental techniques that you may acquire hands-on experience with as a member of my research team are:  - UV/VIS and fluorescence spectroscopy (steady-state, stop-flow, temperature controlled) - computer simulations of DNA duplexes - synthetic organic chemistry (carbohydrate/nucleoside/heterocyclic/organometallic - purification and identification of new compounds using column chromatography, HPLC, SDS-PAGE, NMR, MS, IR, X-ray - solid-phase chemistry (automated nucleic acid synthesis using DNA synthesizers)   Name: Institute: Department: Email: Website:   Dr. Jill Johnson University of Idaho MicrobiologyMBB jilljohn@uidaho.edu   Research:        Once a protein is synthesized it has to both reach the correct location within the cell and attain the proper three-dimensional shape, or fold.  All cells synthesize a group of proteins called ‘molecular chaperones’ that help other proteins fold correctly.  Many human diseases are caused by mutations in proteins that either cause them to misfold (examples are Cystic Fibrosis, Alzheimer’s disease and “Mad Cow” disease), or cause them to become overactive (multiple forms of cancers).  Research in my lab focuses on determining how one type of molecular chaperone, heat shock protein 90 kDa (hsp90), recognizes misfolded proteins and helps them fold. Hsp90 is an essential abundant protein that is required for the activity of a diverse set of cellular ‘client’ proteins.  Many of these client proteins are critical for the development of cancers, and thus inhibitors of Hsp90 are in clinical trials as anti-cancer agents, and show promise in treating various leukemias, breast cancer and prostate cancer. However, Hsp90 is also required for the activity of many other proteins in the cell, and the effects of general inhibition of Hsp90 function on diverse cellular functions is unknown.  Thus it is critical to better understand whether Hsp90 folds all client proteins the same way, or whether there are differences that distinguish the folding of proteins required for general cell growth as opposed to those that promote cancerous growth.  The key to these differences likely lies in the proteins that cooperate with Hsp90 as it folds proteins. These proteins are called co-chaperones, and over a dozen co-chaperones have been identified to date.  The current focus of my lab is to understand how Hsp90 interacts with these co-chaperone proteins and whether different co-chaperones are required for folding of different clients.   Summer Project:   We use the budding yeast Saccharomyces cerevisiae to study the function of Hsp90 and co-chaperone proteins.  This allows us to combine a genetic and biochemical approach to understanding Hsp90 function.  Currently, our efforts are focusing on identifying the similarities and differences in how Hsp90 and co-chaperones interact with very different client proteins, the protein kinase Ste11 and two transcription factors belonging to the steroid hormone receptor superfamily, the progesterone receptor and the glucocorticoid receptor.  These proteins are known to be dependent on Hsp90 in both yeast and mammalian cells and known to have similar interactions with Hsp90 and co-chaperones in both systems.  Using yeast as a model system allows us to study the impact of mutations in Hsp90 and/or co-chaperones on both the physical interaction with Hsp90 client proteins and also the functional interaction with client proteins.  As an INBRE fellow assigned to this lab your research would focus in on picking one or two co-chaperones that are relatively uncharacterized and determining whether that co-chaperone is important for both types of client proteins or just one or the other.  These results would provide novel information about both the function of individual co-chaperones as well as providing important new clues about how Hsp90 mediates protein folding.      Name: Institute: Department: Email: Website:   Alexander V. Karasev University of Idaho Plant Soil & Entomological Sciences alexander.karasev@uidaho.edu www.ag.uidaho.edu/pses/People/fac_pages/p_fac_karasev.htm   Research:        My research program is focused on interactions between plant viruses, their host plants, and insect vectors that transmit plant viruses. We are trying to dissect molecular mechanisms responsible for virus transmission by aphids, and thus providing pathogenicity factors for virus survival and spread. We use methods of reverse genetics, utilizing plant virus based vectors with reporter genes, like green fluorescent protein (GFP). We use two virus models to study virus genes involved in transmission: beet yellows virus, transmitted by aphids semi-persistently; and potato leafroll virus, transmitted persistently. We target individual genes of the viruses through site-directed mutagenesis and subsequent screening of the resulting phenotypes.     Summer Project:        Spread and survival of aphid-transmitted viruses depend on interactions between the virus, the vector, and the host plant. For phloem-limited viruses, like potato leafroll virus (PLRV) or beet yellows virus (BYV), aphid transmission often functionally overlaps with vascular movement of the virus through the plant, and with virion assembly. BYV genome encodes five genes responsible for the local, cell-to-cell movement and at least one gene, p20, involved in vascular movement; most of the same genes are involved in virion assembly. To dissect overlapping effects of vascular spread, aphid transmission, and assembly, a series of mutations have been generated in the p20 gene. An infectious cDNA copy of the BYV genome, will be used to screen these mutants for the loss of long distance movement and/or aphid transmission phenotype in a Nicothiana benthamiana/Myzus persicae model. These screenings will be facilitated by the presence of a reporter gene, GFP, in the BYV cDNA clone, which can be tracked by a simple epifluorescent microscopy. We thus expect to dissect molecular mechanisms of BYV responsible for the long distance spread and aphid transmission, and subsequently map protein domains involved in these processes.  For PLRV, we are looking at mutants with altered volatiles profile or lost ability to attract aphid vectors.           Name: Institute: Department: Email: Website:     Dr. Kevin Kelliher University of Idaho Biological Sciences kelliher@uidaho.edu http://www.sci.uidaho.edu/biosci/faculty/kelliher.html Research:  My research program addresses fundamental behavioral and physiological questions about how chemosensory stimuli mediate behavior. Research projects in my lab address these questions at cellular, systems and behavioral levels. One avenue of investigation is addressing the relative roles of different chemosensory systems or subsystems for the processing and perception of chemosensory cues that influence social behavior.  In the nasal cavity of vertebrates there are multiple different chemosensory systems that potentially detect social cues.  It has become increasingly important to understand how these different systems interact to accurately perceive a chemosensory cue and result in the appropriate behavioral output. In the lab we utilize mice with targeted deletions of genes critical for signal transduction the different olfactory subsystems.  This allows us to study the processing individual cues by each olfactory subsystem independently.  Establishing and conducting behavioral assays for the detection of different cues has also become a critical tool for the study of each system. Summer Project There are currently two projects going on in the lab that would provide excellent experience for undergraduate students during the summer.  The first project involves studying the role of the cyclic nucleotide gated ion channel transduction pathway in the Guanylyl Cyclase –D olfactory receptor neurons.  Very little is known about this particular olfactory subsystem, however, recent studies have suggested that it may detect two very different classes of cues.  There is evidence that these receptor neurons may detect both CO2 at near atmospheric levels and also peptide ligands produced in the gut of mammals.  We are in the position study this system since we posses a strain of mouse that lacks the primary CNG subunit for signal transduction.  We intend to behaviorally study CO2 attraction/aversion in these mice.  The second project investigates the relative roles of the main olfactory and vomeronasal systems in the acquisition and display of social dominance.  While we know that both systems function in this s regard the exact roles of each system and the particular chemical cues utilized by each system are still in question.  Using different candidate cues  (Pheromones) we will systematically study the ability of a mouse to become socially dominant and display this dominance when one or both olfactory systems are impaired.  Again we have transgenic mice with defects in particular proteins that are required for signal transduction in one or both of these systems.  These mice will allow us to independently each of these olfactory subsystems.   Name: