Training Laboratory Research
Below are short descriptions of the ongoing research in each of the training laboratories:
J. Alderete (SMB): Trichomonas vaginalis, the number one, non-viral sexually transmitted organism, is the focus of our research program. The study of parasite and host cell-tissue interactions is focused on the identification of surface proteins that contribute to infection and disease pathogenesis. We study several important properties of the biology of the parasite and the host-parasite interaction. These include antigenic diversity, cytoadherence, immune evasion, iron acquisition, and the dsRNA virus infection.
N. Abu-Lail (ChE/BE): Investigating microbial interactions and virulence constitutes the main focus of our lab. Our current microbes of interest are the Listeria family. Listeria monocytogenes are unique food-borne pathogens capable of infecting humans and animals. Our ability to explain and control the adhesion and virulence of Listeria to surfaces is limited by the lack of molecular-scale studies on how the surface biopolymers of L. monocytogenes affect their virulence and attachment to surfaces. Our long-term objective is to explore the molecular effects of the surface biopolymers of virulent and avirulent L. monocytogenes on their initial attachment to surfaces in a wide array of environmental conditions.
H. Aguilar-Carreno (SGAH): Our lab’s primary research interest is the elucidation of the mechanisms of entry of enveloped viruses into mammalian host cells. Viral-cell membrane fusion is a crucial step during entry of enveloped viruses into their mammalian host cells. In addition, for some viruses (e.g. some paramyxoviruses), viral infection induces the pathological cell-cell fusion (syncytia). Our lab uses multidisciplinary approaches to study viral-cell and cell-cell membrane fusion that combine the fields of biochemistry, molecular biology, immunology, and biophysics to focus mainly on the deadly Nipah and Hendra viruses as model systems.
P. Benny (Chemistry): Our research group focuses on the development of new techniques and compounds utilizing radioactive nuclides for diagnostic and therapeutic applications in nuclear medicine. The overall goals of the research stem to improve the translation of radiolabeled compounds to practical application through the “bench top to clinic” development. In recent years, Dr. Benny has specifically focused on developing novel small molecule and peptide targeting agents for prostate cancer with Alberto’s reagent.
C. Berkman (Chemistry): Synthesis, resolution, and biochemical evaluation of chiral phosphorus-containing inhibitors of metallopeptidases related to cancer, folate processing, and neurodegenerative diseases.The research in my laboratory is primarily concerned with design of novel enzymes inhibitors for the use in sensitizing tumor cells to common chemotherapeutic strategies. Specifically, we are interested in phosphorus- and sulfur-containing transition-state analogs inhibitors of these target enzymes. To this end, we focus also on the preparation of conformationally restricted substrates for such enzymes in order to probe their structural requirements and to ultimately design analogous inhibitors with enhanced selectivity.
H. Beyenal (ChE/BE): Work in the Beyenal laboratory focuses on microbial biofilms and bacterial adhesion processes in the context of environmental microbiology and environmental contaminants. Specific research topics in the laboratory include: measuring biofilm parameters with microsensors, microbial fuel cells, electron transfer mechanisms, and bioremediation.
M. E. Black (SMB): Research in the Black laboratory centers on nucleotide metabolizing enzymes as targets for chemotherapeutic drugs and anti-infective compounds. Her primary focus is on the application of enzymes in gene therapy protocols to sensitize cells to nucleoside analogs for tumor ablation. A more recent interest in the laboratory is in the molecular basis of drug resistance within such drug targets that are often associated with treatment failure. Black’s work seeks to explore the molecular basis of enzyme function using a combination of molecular evolution strategies (e..g., random and site-specific mutagenesis followed by selection) plus molecular modeling based on structures derived from x-ray diffraction and NMR studies, to generate novel functional enzymes. A practical extension of these studies is to create mutants with improved substrate or prodrug activities. Such mutants not only reveal important functional motifs but are also highly desirable for enhancing gene directed pro-drug therapies in the treatment of cancer.
K.A. Brayton (VMP): Research in the Brayton laboratory focuses on antigenic variation and microbial genomics of vector-borne diseases, specifically on the infection biology of the tick-borne pathogen Anaplasma marginale. The recently completed genome sequence of A. marginale helped the laboratory elucidate the gene conversion mechanism of antigenic variation of msp2 and msp3, two variable major surface proteins of A. marginale. The lab continues to study these genes and surface proteins to understand their role in the evasion of the immune response and lifelong persistence of the organism in the vertebrate host.
W. Brown (VMP): Research in the Brown laboratory seeks to develop vaccines that will fight infections transmitted by insects, such as bovine babesiosis, and bovine anaplasmosis. These infections can result in anemia in cattle, particularly in hot environments. In the Brown laboratory pathogen proteins are identified that elicit an immune response in the host animal. A method developed by the Brown lab team determines these proteins by rapidly screening various antigens. The Brown laboratory is also part of a group of scientists funded by the Bill and Melinda Gates Foundation to develop an improved vaccine for East Coast fever, a serious tick-borne cattle disease prevalent in sub-Saharan Africa.
J. Browse (IBC): Research in the Browse laboratory centers on the enzymology of lipid synthesis in plants and on the role of lipid compounds in plant biology usingArabidopsis as a model. Projects of interest to biotechnology students include 1) molecular-genetic manipulation of the fatty acid composition of seed oils, 2) the action of lipid-derived hormones in reproduction and plant defense, and 3) investigating the mechanisms of low-temperature tolerance in plants. A second program uses mutational analysis and molecular genetics to investigate lipid structure and membrane function in the model nematode Caenorhabditis elegans. Students can expect to receive broad training in protein biochemistry, molecular genetics and cell biology and to benefit from industrial collaborations that form the basis for some of these projects.
D. Call (VMP & SGAH): There are two central premises that guide the activities of the Call lab. 1) The fact that, with few exceptions, bacterial species encompass considerable genetic diversity. This is best illustrated through whole genome sequences that have shown that less than half of the genes carried by a given strain of Escherichia coli are necessary to “make” an E. coli. The remaining genes are presumably used to equip different strains to reside in specific niches. 2) The Theory of Natural Selection that leads to the prediction that the distribution of genetic diversity within a species is not random. If genetically encoded traits lend fitness advantages in different niches, then natural selection will order the variation within a species. These two premises lead us to conclude that by studying the distribution of genetic diversity we can make inferences and formulate hypotheses about hot pathogens make their living. This conclusion motivates much of the research in my laboratory involving a diverse array of organisms. Our primary focus is food-and water-borne disease agents that are bacterial, although we work on a number of other projects both independently and collaboratively.
R. Carabeo (SMB): My laboratory conducts research on the interaction of the human pathogen Chlamydia trachomatis with the epithelium. The principal research question we are addressing is the mechanism by which Chlamydia subverts host cell signaling to hijack the host cytoskeleton and vesicular transport to facilitate infection and nutrient acquisition. We are Specific topics include the following: invasion of non-phagocytic cells,mModulation of host cell focal adhesions, and iron homeostasis in Chlamydia.
J. Celli (SGAH): Our research group is studying the mechanisms of intracellular survival and proliferation of Brucella abortus, the causative agent of the world-wide zoonotic disease brucellosis. Our primary research goal is understanding the functions of Type IV secretion effector proteins in Brucella abortus intracellular pathogenesis and the role of the host autophagy pathway in Brucella dissemination. Our current work towards characterizing bacterial and host factors contributing to Brucella-host cell interactions can be used to define targets for the development of new treatments against the disease.
R. Croteau (IBC): Retired April 2012. Our research deals broadly with the origin, metabolism and function of terpenoids in plants, and more specifically with the monoterpene (C10), sesquiterpene (C15) and diterpene (C20) constituents of the essential oils and resins used in pharmaceuticals, nutraceuticals, flavors, fragrances, and as industrial raw materials. These low molecular weight terpenoids provide a means of chemical defense and communication in plants, yet these compounds are also catabolized during development, suggesting a metabolic role in addition to the ecological function.
A. Dhingra (MPS): The research program of the Dhingra laboratory focuses on understanding important biological phenomenon in horticultural crops. The research integrates transcriptomics, molecular biology, plant physiology, functional and translational genomics and proteomic approaches to identify gene(s) and proteins participating in a biological process in order to establish time saving and cost effective methodologies for effective horticultural crop improvement.
W.J. Dong (ChE/BE): Research in my lab is multi-disciplinary, involving cardiac muscle biology and mechanics, protein chemistry and engineering, fluorescence techniques, computer modeling, nanoscale biosensor design and engineering. Our long-term research objective has two components. The first component focuses on the understanding of the Ca2+ switching mechanism of cardiac myofilament in healthy and diseased hearts. Cardiac muscle contraction is initiated by Ca2+ binding to cardiac troponin C triggering a series of functional structural changes within the thin filament. These serious structural transitions are regulated by both Ca2+ binding and cross-bridge cycling, and modulated by protein phosphorylation and cardiomyopathy mutations.
D. Gang (IBC): Our research seeks to elucidate the biosynthetic pathways that produce novel and important plant specialized metabolites in aromatic plants, to uncover the mechanisms responsible for the evolution of these pathways in the plant kingdom and to understand the function of a given natural product in the biology and physiology of a given plant species. Besides the intrinsic scientific value of understanding plant metabolism and how plants produce specific natural products, such knowledge is essential for rational custom-designed breeding (by classical methods) of targeted natural product profiles in chemically tailored plants. This knowledge is also essential for the application of genetic engineering techniques to improve and develop new aromatic plants.
A. Goodman (SMB): Our research focuses on the immune response to pathogenic infection. In addition to experimental laboratory techniques, we utilize mammalian and invertebrate animals models along with mathematical modeling and high-throughput computational analyses to further understand the cellular signaling pathways during infection. The complementary use of these techniques across multiple animal models will guide us to better therapeutically intervene during autoimmune, microbial, and vector-borne disease.
M. Hardy (VMP): Our laboratory studies enteric virus-host cell interactions in the context of the cell intrinsic antiviral defense response, and immune responses that are initiated and regulated at the gut mucosa.We have a long-standing interest in how viruses have evolved to modulate the interferon (IFN)-mediated antiviral response, and the cellular proteins in key signaling pathways that viruses target for inhibitory activity. Specifically, we have studied the enteric rotavirus, a virus that is ubiquitous and causes life-threatening gastroenteritis in neonatal domestic livestock and in children. Our current studies seek to understand the breadth of molecular mechanisms rotaviruses use to modulate the antiviral response to facilitate replication and spread in the gut.
C.A. Haseltine (SMB): Work in the Haseltine laboratory focuses on the mechanism of double-strand break (DSB) repair of DNA using a thermophilic archaeal model system. Through a multidisciplinary approach, the laboratory is dissecting DSB repair mechanisms in the hyperthermophilic archaeon Sulfolobus solfataricus. Using in vivo mutational analyses coupled with a DSB assay system the research is establishing, for the first time, the cellular function of archaeal recombination proteins. To complement these studies, the laboratory is systematically investigating the recombination proteins in vitro. Each protein is heterologously expressed, purified, and examined for its role during DNA strand exchange. Through these combined approaches, they are establishing a comprehensive understanding of the basic mechanism of homologous recombination with the goal of elucidating the more intricate eukaryotic process.
M. Kahn (IBC/SMB): This research program is interested in the biochemistry, genetics and physiology of intermediary metabolism in the nitrogen-fixing symbiosis between Sinorhizobium meliloti and alfalfa. Current funded projects in the laboratory employ a proteomics approach to clone and genetically manipulate the 6200 predicted proteins in S. meliloti, investigate the basis of dicarboxylic acid transport in the bacteria and the mechanisms of energy transduction that lead to nitrogenase. This laboratory also investigates the genetics and biochemistry of the plant contribution to a productive symbiosis. Trainees in this group use a full range of molecular and genetic tools to probe the protein chemistry of symbiotic interactions.
C-H. Kang (Chemistry): Dr. Kang is the Director of the WSU X-ray Crystallography Facility and the research of his laboratory focuses on studies protein-nucleic acid interactions at the molecular/structural level. This group is trying to identify alterations in the structure of DNA induced by a variety of DNA damaging agents. Recently they published the crystal structure of a DNA decamer containing a thymine-dimer, the main lesion product produced by exposure of DNA to UV light. The group is also studying the means of recognition of altered DNA by a repair enzyme and the interaction of repair enzymes with damaged DNA. Dr. Kang is convinced that a better understanding of the structural details of DNA damage and repair will help pave the way to risk assessment based on the mechanics of carcinogenesis. He is currently carrying out x-ray studies of several enzymes involved in a process that maintains the integrity of the genome including nucleotide excision repair of damaged DNA. Trainees in this laboratory will not only first-rate training in the rapidly expanding field of macromolecular x-ray crystallography but will also become proficient in the production, characterization and study of proteins and protein-nucleic acid complexes.
K.H. Kim (SMB): The Kim laboratory is interested in why vitamin A is essential for testis function during embryonic and postnatal development. As vitamin A signals through the retinoic receptors (RAR), the laboratory is interested in the regulation and function of these protein receptors during testis development. Their research includes the study of protein phosphorylation of the retinoic receptors and identification of target genes and proteins regulated by the retinoid receptors. A second, toxicoproteomics based approach is being used in the laboratory to determine whether RARa and PPARa change their phosphorylation patterns after treatment of Sertoli and liver cells with phtalates and triglyceride lowering drugs. Students in this laboratory receive extensive protein biochemistry and proteomics training related to retinoic acid receptor signaling.
H. Kirchhoff (IBC): Plants are integrated in a complex environment that fluctuate both randomly and periodically on very different time scales. Photosynthetic energy conversion must compensate for these changes to maintain energetic homeostasis for the cell. Failure to do this results either in reduced performance of energy transformation and consequently in a decrease in yield and fitness of plants or in severe damage by toxic photosynthetic side products that eventually lead to cell death. These potential problems are tackled by a battery of highly regulated optimization, protection, and repair mechanisms. Most of these mechanisms are realized in the photosynthetic thylakoid membranes that harbor the sophisticated, structured nanomachines responsible for biological energy conversion. Our research aims to understand the mechanisms that optimize, protect, and maintain the photosynthetic machinery on the molecular and supramolecular level. Accomplishment of these ambitious aims will lead to insights on how plants survive in an challenging environment and can help to find new strategies to solve our global food and energy problems.
M. Konkel (SMB): The Konkel research group focuses on the characterization of host-C. jejuni interactions. Biochemistry, cell biology, molecular biology, and genomic/proteomic approaches are currently being used to understand the unique virulence factors that contribute to the pathogenesis of this facultative intracellular bacterium. One of our current aims is to identify and characterize cell binding and entry-promoting proteins used by C. jejuni to cause disease.
A. Kostyukova (ChE/BE): Our research focus is the regulation of actin dynamics by actin binding proteins. Of the many possible mechanisms that might influence these dynamics, we explore three that appear to be the most likely: (1) isoform dependence in Tmod/TM interaction, (2) identification of still unknown Tmod binding partners that change Tmod functional abilities and (3) Tmod phosphorylation.
L. Knodler (SGAH): The overall aim of our research is to elucidate bacterial and host factors that dictate the intracellular fate of Salmonella enterica in intestinal epithelial cells, with the ultimate goal of gaining a better understanding of how enteropathogenic bacteria cause diarrheal disease.
H. Kunz (MPS): The long-term goal of the research in the Kunz lab is a systemic understanding of the chloroplast ion homeostasis, the dynamics and how this feeds into photosynthesis and energy storage. Moreover, we are exploring how the chloroplast fights abiotic stress and which transporter genes and other genetic components are involved in this process. Identified genes from this research will be tested for their potential to increase photosynthetic efficiency under unfavorable environmental conditions.
Mark Lange (IBC): Plants produce a diverse array of metabolites, the majority of which does not appear to be directly involved in growth and development. These metabolites are commonly referred to as secondary metabolites, specialized metabolites or natural products. In contrast to primary metabolites, which are found in all plants and are usually involved in essential processes (e.g., acyl lipids, amino acids, chlorophylls, hormones, nucleotides, organic acids, phytosterols, sugar phosphates, vitamins), natural products oftentimes play more elusive roles in the communication of plants with their environment (e.g., protection against herbivores and infection and attraction of pollinators and/or seed dispersers) and are differentially distributed. Plant natural products are better known for their utility as dyes (e.g., indigo), fibers (e.g., cellulose), flavors (e.g., d-limonene from Citrus), fragrances (e.g., geraniol from Damask rose), and drugs (e.g., morphine). Research in the Lange laboratory is aimed at characterizing the interface between primary and secondary metabolic pathways using functional genomics and systems biology approaches.
N.G. Lewis (IBC): The main interests of the Lewis laboratory are gaining a detailed molecular understanding of the biochemical basis for various phenylpropanoid radical-radical coupled reactions, particularly those involved in lignan formation, lignin initiation and biopolymer assembly in plants. A second goal is in gaining knowledge as to how various genes function in a particular woody plant species to provide the different reinforced structural tissues and organs unique to the land plants, e.g., sapwood, heartwood, the vascular apparatus, branching tissues, etc. A third goal is in defining how the various medicinally important lignan skeleta are formed in various plant species, many of which have antibacterial, antifungal, antiviral and anticancer properties.
R. Mancini (Chemistry): The Mancini research group uses the molecular control of chemistry to effect macroscopic changes in biological and physical systems. Researchers in the lab acquire expertise in synthetic organic chemistry, polymer chemistry, and chemical biology while working in several key research areas, including 3D printable cell cultures, cancer immunotherapeutics, and synthetic macromolecular asymmetry.
N. Magnuson (SMB): Retired Spring 2015. The Magnuson lab focuses on the regulation of the cell cycle, and post-translational modifications of cancer related proteins. With specific emphasis of the photo-oncogene PIM1 cell survival and proliferation, leading to tumorigenesis is investigated.
M. Neff (CSS): Our lab uses molecular, genetic and biochemical approaches to uncover and describe the interactions between various signaling pathways that modulate plant development. Specifically, we use seedling development in the plant Arabidopsis as a tool for addressing the question: How do signaling pathways modulated by light interact with each other and with those regulated by endogenous hormones to control plant development? Our lab’s research relates to the goal of increasing yield in agricultural crops by studying the photomorphogenic and hormone signaling pathways that regulate plant stature.
A. Nicola (VMP): Our research focus is infectious diseases, namely herpes simplex virus, and its virus-cell interactions. We utilize a combination of cellular, molecular, biochemical, and microscopic approaches to delineate the step-by-step itinerary of the incoming virus. A better understanding of how herpes simplex virus interacts with the cell will identify novel targets for intervention.
A. Omsland (SGAH): Our research is on Coxiella burnetii and Chlamydia trachomatis. Our research has focused on understanding physiochemical and nutritional requirements of obligate intracellular parasites and development of host cell-free (axenic) culture techniques to facilitate their physiological analyses. Long-term research interests include nutritional regulation of pathogen virulence and developmental cycles, and the metabolic basis of persistent infections.
G. H. Palmer (VMP & SGAH): Palmer and colleagues use a combined genomic and proteomic approach to identify new vaccine targets and to develop novel delivery systems to optimize the immune response. The key to their approach is identifying the immune cells that kill the microbe and then use these cells in functional assays in a comprehensive search of all microbial proteins. Using a proteomics approach combined with the complete microbial genome sequences allows identification of the vaccine candidate proteins. This approach differs markedly for those previously used to identify candidate proteins in that it directly couples the immune function to protein identification- without bias as to location or function of the protein itself. The goal is to develop new vaccines against microbial pathogens and use immunization to protect animal and public health. Microbes currently being targeted include tick-transmitted pathogens of animals and humans and bacterial agents of risk for use in bioterrorism.
R. Reeves (SMB): Retired July, 2015. The Reeves lab investigates the structure of DNA and proteins affect components of normal cells versus cancer cells. Specifically, research in the Reeves lab is focused on the protein HGMA, which can bond to and then change the structure of DNA. This protein is often over-expressed in cancer cells.
S. Roberts (SMB): Mutations and chromosomal rearrangements underlie a variety of diseases from autism to cancer. What causes these genetic alterations, however, is frequently unclear. Recent large scale re-sequencing of human tumor genomes has revealed that cancer is a complex set of diseases, with tumors displaying different clinical and cellular characteristics. Along with these phenotypic differences, tumors have varying mutation frequencies and mutagenic processes occurring that ultimately impact aspects of disease onset, progression, and ultimately drug resistance. The focus of my lab is to understand the plasticity of genomes and how such alteration contributes to each of these aspects of carcinogenesis. We use biochemical, genetic, and genomic approaches to probe these questions.
K. Sanguinet (MPS): Research themes in the Sanguinet lab focus on factors that modulate growth and development. We study the root architecture of the Pooideae subfamily of temperate grasses using developmental, genetic and genomics approaches. Through characterization and analysis of a suite of root mutants and natural accessions in Brachypodium distachyon, we hope to gain insight into the quantitative and qualitative control of homorhizic root architecture typical of the grasses. We are also interested in understanding the link between hormonal crosstalk and how the cell wall constrains morphogenesis.
D. Shah (VMP & SGAH): Research in the Shah lab is mainly focused on molecular pathogenesis of Salmonella in human and avian hosts. The Shah lab has identified several Salmonella strains that are closely related genetically but differ in several phenotypic characteristics including pathogenicity using in vitro and in vivo animal model systems such as mice and chickens. The lab continues to study these strains using high-throughput comparative functional genomics, proteomics and next generation sequencing approaches to identify gene/protein targets that contribute to pathologic processes. The long term goal of this research is to identify targets for the development of newer vaccines and diagnostic tools. Other areas of research include food safety and public health; more specifically, developing control strategies for Salmonella and Campylobacter infection in human and avian hosts, understanding the biology of these pathogens in avian hosts and studying dissemination of antibiotic resistance in pathogenic and commensal microbial populations in animals and humans.
E. Shelden (SMB): My laboratory is investigating the regulation and function of Hsp27 in developing zebrafish embryos using molecular and biochemical methods, as well as fluorescence microscopy. We recently reported that Hsp27 can associate with basolateral cell junctions in epithelial cell monolayers and co-localize with actin, at the level of the light microscope, in at epithelial cell-cell junctions and developing myofibrils. We are expressing Hsp27 mutants in zebrafish embryos and testing these mutants for their ability to interact with cytoskeletal complexes, promote survival and protect cell function from disruptions in embryos exposed to heat shock, reactive oxygen species, annoxia and a variety of environmental toxins. These studies employ fractionation followed by immunoblotting, as well as assays of apoptosis and cell survival using LDH release and fluorimetric quantification of nucleic acid content. In addition, we conduct fluorescence localization studies using immunofluorescence and analysis of expressed fluorescent fusion proteins in transiently and stably transformed fish lines. We also test interaction of Hsp27 with fluorescent fusion proteins of cytoskeletal proteins using Forster resonance energy transfer (FRET) methods.
M. Smerdon (SMB): Research interests in the Smerdon lab include DNA damage and repair in eukaryotes, chromatin structure and function, and carcinogenesis, cancer prevention and treatment.
K. Tanaka (MPS): Extracellular ATP is one of the DAMP signals in both animals and plants. Although ATP is well-known as the energy currency molecule in the living cell, once ATP is released into the extracellular space following cellular damage, it acts as a DAMP signal. Our research focuses on the function of this DAMP signal for in-depth understanding of plant defense mechanisms against pathogen and insect attacks. Based on our research, we would further like to determine how we can improve plant growth and vigor and therefore increase crop yields. We also focus on a project to implement integrated control strategies for potato powdery scab disease, which has in recent decades insidiously spread in many regions where potatoes are grown, including most potato production areas in Washington State.
V. Vadyvaloo (SGAH): Our research focus is in the transmission and persistence of the etiological agent of the bubonic plague, Yersinia pestis. Our goal is to obtain an understanding of the genetic basis of bacterial pathogen transmission and persistence using molecular approaches and of the persistence and re-emergence of the plague using both fleas and protozoa as host models.
B. Van Wi (ChE/BE): Prof. Van Wie is engaged in research in various aspects of biotechnology including biosensors and bioanalytical devices, and cell and tissue culture. Also, he has been quite successful in the area of Engineering Education Research and currently is engaged in a second National Science Foundation Type II Course, Curriculum and Laboratory Improvement grant effort and interacts with several universities as a result including eight institutions in Nigeria where he and his family recently did a Fulbright exchange.
S. Wang (SMB): The Wang laboratory investigates radical mechanisms in protein enzyme catalysis. Specifically she investigates molecular interactions involved in the activity of the “radical SAM (S-adenosyl-L-methionine)” enzyme superfamily believed to catalyze interesting and difficult methyl transfer reactions required by some organisms for antibiotic biosynthesis.
J. Watts (SMB): Our lab is interested in the mechanisms through which the physical properties and regulatory actions of specific lipids impact the cell biology and physiology of animals. The implications of this research extend from understanding how specific fatty acids affect cell signaling to dissecting the fat regulatory pathways involved in obesity and related diseases. We use the nematode model Caenorhabditis elegans and a combination of genetic, genomic and biochemical approaches to understand the regulation, function and biosynthesis of unsaturated fatty acids.
J.J. Wyrick (SMB): The Wyrick laboratory investigates the cellular responses of the yeast Sacchromyces cerevisiae to environmental or developmental signals by reprogramming the expression of specific genes. In particular his work focuses on the role genome-wide histone modification patterns in regulating yeast gene expression. More recently his work has focused on the regulation of gene transcription by the histone H2A and H2B N-terminal domains.
R. Yount (Chemistry): Emeritus. Professor Yount’s primary interests are in the molecular mechanism of muscle contraction and of motility in biological systems. His group prepares new analogs of ATP to be used as monitors of contractile events and/or as probes of the molecular structure of contractile proteins. Some recent derivatives contain stable free radicals (spin probes) or fluorescent/luminescent probes attached to ATP or ATP-like molecules that also contain photo reactive groups capable of forming covalent bonds to proteins upon irradiation of the appropriate complexes. These probes are then covalently bound near the ATP-binding site and have been found not to interfere with contractile events. We “trap” the ADP product of hydrolysis of these ATP-like molecules at the active site of myosin (the major contractile protein in muscle) with transition state analogs of inorganic phosphate, e.g., vanadate or AlF4. Extraneous ADP analog is removed by washing and myosin then photo labeled specifically in a benign manner. Thus it is possible for the first time to introduce EPR or fluorescent/luminescent reporter groups onto the “heads” of myosin in a specific manner even in complex muscle fibers. This approach allows us to monitor the movement of the heads during the contractile cycle. Other studies are aimed at using these new derivatives to reveal the nature of force generation by kinesin and kinesin-like molecules that move on tracks of microtubules.