Trainee Research Opportunities
The training faculty provides wide-ranging expertise in most areas that are central to contemporary protein biochemistry, biology and proteomics, both in their basic and applied aspects.
These Research Areas Include:
(1) Protein production, targeting and export:
Alderete , Black , Gloss , Griswold, Hatefi , Her , Ivory, Kang , Lewis, Magnuson, Palmer, Reeves,
(2) Enzyme catalysis and metabolism:
Black, Browse, Gloss, Jones, Kahn, Kim, Kramer, Lewis, Wang and Xun
(3) Recognition of small and macromolecules:
Alderete , Beyenal, Black, Brayton, Brown, Davis, Her, Gloss, Jones, Kim, Magnuson, Nilson,
Palmer, Reeves, Skinner, Smerdon and Van Wie
(4) Signaling receptors and transduction:
Griswold, Her, Kahn,
Kim, Koh
, Kramer, Magnuson, Nilson, Skinner and Steber
(5) Covalent protein modifications:
Brown, Gloss, Griswold, Kahn, Kang, Magnuson, Palmer, Reeves, Skinner, Smerdon and Wyrick
(6) Macromolecular structure:
Black, Davis, Gloss, Jones, Kang, Reeves and Wang
(7) Gene Regulation and DNA repair processes:
Black, Brayton, Brown, Call , Davis, Dhingra, Griswold, Haseltine, Her, Kang, Kim, Koh ,
Magnuson, Nilson, Palmer, Reeves, Shelden , Skinner, Smerdon and Wyrick
(8) Proteomics:
Brown , Griswold , Ivory , Jones , Kahn , Kim , Palmer and Skinner
Top
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.
H. Beyenal (ChemE): 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 (Pharm/Tox): 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.C. Brown (VMP): The Brown laboratory's research emphasis is on understanding the bovine helper T cell response to vector-born hemoparasites and molecularly defining immune mechanisms and targeted protein antigens. Because the intracellular parasites Babesia bovis and Anaplasma marginale reside exclusively within erythrocytes, the focus of her research is on MHC class II-restricted, CD4+ T cell responses, IgG responses and macrophage activation. Specific studies involve understanding immunological control mechanisms of Babesia and Anaplasma infections, defining helper T cell responses to conserved and variable regions of immunogenic proteins, using helper T lymphocytes from immune cattle to identify novel protective antigen proteins that can be used in a subunit or nucleic acid based vaccine, and defining the role of protein antigenic variation in helper T cell epitopes in persistent infection by these organisms. A mass spectrometry/proteomics approach towards identifying novel A. marginale outer membrane proteins that stimulate memory CD4+ T cells responses is being pursued, facilitated by the nearly complete sequence of the genome of this organism. These major areas of research emphasis provide opportunities for graduate students to study immune mechanisms against different types of parasitic pathogens in an outbred species, and provide a unique training environment that combines molecular and cellular approaches towards understanding the host-parasite interaction that results in protective immunity or successful parasitism.
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 using Arabidopsis 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): 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.
W.B. Davis (SMB): Research in the Davis laboratory centers on investigations into the mechanism of DNA damage and repair and the effects of exogenous and endogenous oxidants on genomic and mitochondrial DNA in mammalian cells.
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.
L.M. Gloss (SMB): The Gloss laboratory investigates the assembly and folding of proteins and enzymes, particularly oligomeric systems. Eukaryotic histones and nucleosome core particles, as well as dihydrofolate reductases from E. coli and the archaeal extreme halophile, Haloferax volcani, are experimental models systems employed in folding studies.
M.D. Griswold (SMB): The Griswold laboratory is prominent in the area of testis reproductive biology and for its emphasis on protein biochemistry as a tool to investigate the mechanisms by which hormones alter gene expression and thus produce cell differentiation during gonad development. The laboratory is also heavily involved in the genomic and bioinformatics analysis of gene expression patterns during various developmental stages of the mammalian testis. Trainees in this research program would gain experience in the use of protein chemistry to study hormones, their receptors as well as the modification and targeting of secreted proteins.
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.
A. Hatefi (Pharm/Tox): The Hatefi laboratory utilizes genetic engineering, biomolecular engineering, bioengineering, cell biology, and polymeric gene/drug delivery to create systems that can be programmed to perform multiple functions. The main goal of the laboratory is to design a delivery system that can be programmed to evade the immune system, adapt to its environment, find its target and deliver therapeutically relevant molecules to the target cells with high efficiency/toxicity ratio.
C. Her (SMB): Research in the Her laboratory involves investigation of the mechanisms and proteins involved in mammalian cell DNA mismatch repair pathways. A primary focus of the research is on the role of the MutS homologues hMSH4 and hMSH5 with diverse functional implications in humans.
C.F. Ivory (ChemE): The Ivory laboratory is interested in developing instrumentation and protocols for high-performance biological separations, particularly of proteins, at scales ranging from grams down to micrograms, especially using electric fields. Current projects use various techniques, including counteracting gradient electrofocusing as a replacement for isoelectric focusing, in multi-dimensional separation cascades capable of isolating low-abundance proteins from complex mixtures, e.g., tissue and cell homogenates, blood sera and fermentation broths. His recent research also focuses on alternative methodologies for separating various protein components of highly complex mixtures as a first step in proteomic studies involving mass spectrometry to identify individual proteins. Dr. Ivory believes that chemical engineers will play an ever-increasingly important role in shaping both the biotechnology industry and molecular medicine. In this context, is attempting to develop and commercialize a simple and quick way to easily identify protein biomarkers that indicate a patient is at risk of suffering a heart attack before they show symptoms. Trainees with an interest in chemical engineering could pursue appropriated thesis work in this laboratory while acquiring a solid background in biological and biochemical sciences.
J.P. Jones (Chem): The Jones laboratory investigates biosynthetic pathways for the oxidation of hydrocarbons in mammalian cells. His laboratory uses experimental, computational and predictive models for the cytochrome P450 enzymes that can be used as tools in risk management and the prediction of metabolic disposition of drugs and environmental contaminants in humans. In particular, his research focuses on the prediction of human drug toxicity caused by P450-mediated bioactivation. Students in his laboratory receive excellent and extensive training in protein chemistry, enzymology and toxicoproteomics.
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 (SMB/Chem): 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.
D. Koh (Pharm/Tox): Cells possess multiple mechanisms to respond to genomic stress, or damage to the genetic material required for normal functioning and development. These mechanisms usually end with either the return to normal cellular function after DNA repair or the induction of cell death. Between the detection of DNA damage and the life or death outcome, there are many signaling events. My laboratory is interested in the cellular and molecular mechanisms which ultimately determine these cell fates. Insight into these events should lead to better strategies to treat conditions caused by the inappropriate survival of cells, such as cancer, or the inappropriate death of cells, such as stroke. Specific research areas in the lab include investigating: 1) Molecular and cellular mechanisms of cell death; 2) Cell signaling events in response to toxic chemicals that determine cell fate; and, 3) Genetic disruption techniques for in vivo cell death models.
D.M. Kramer (IBC): The Kramer research group seeks to understand how plants convert light energy into forms usable for life. His studies the fundamental mechanisms of the light reactions of photosynthesis and the mechanisms of biochemical redox reactions and proton pumps in vivo in plant cells employing non-invasive biophysical, biochemical, molecular and physiological approaches. Photosynthetic enzymes are studied using spectroscopic approaches including absorption, fluorescence, circular dichroism and electron spin resonance (EPR) applied to isolated membranes, organelles and intact plants. The laboratory is pioneering the development of non-invasive approaches to study the proteins of photosynthesis in living plants. Students in the laboratory gain wide exposure to biophysical techniques and the important area of bioenergetics.
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.
N.S. Magnuson
(SMB):
The primary interest of this laboratory is determining
the normal function of the proto-oncogene Pim-1 kinase,
determining how its over-expression causes cancer and
establishing how its expression is regulated under normal
and physiological conditions and during
tumorigenesis. Investigations of
oncogenic proteins like Pim-1 are of considerable
interest to biotechnology firms and major pharmaceutical
companies and, thus, the work of this laboratory is at
the interface between basic and applied
approaches.
J. Nilson (SMB): The Nilson laboratory is testing three major hypotheses that will deepen our understanding of how the GnRH signal crosses the transcriptional network and culminates in the regulation of the four signature genes. First, while it is clear that GnRH regulates transcription of Egr1 through convergence of multiple signaling pathways, we postulate that post-transcriptional and post-translational mechanisms contribute to the concentration and activity of the EGR1 protein as they do for other members of the IEG family. Second, new evidence indicates that GnRH regulates ß-catenin via cross-talk with downstream members of the canonical WNT signaling pathway, suggesting a new signaling route for regulating expression of Jun and possibly other IEG mRNAs. Third, we propose that ß-catenin also acts independently of GnRH to support the permissive role of SF1 in allowing all four signature genes to respond to GnRH.
G. H. Palmer
(VMP):
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): This laboratory has a
long-standing interest in how the mammalian “High
Mobility Group” (HMG) nonhistone proteins regulate
chromatin structure and function. His
research focuses on how binding of HMGA proteins to gene
promoter regions regulates inducible gene transcription
and also on how these proteins function to promote
cancerous transformation and metastatic progression of
tumor cells. More recently his
interests have turned to investigation of the role that
HMG proteins play in DNA damage and repair processes in
human cells. Trainees in this
laboratory receive broad training in the fundamentals of
protein chemistry, purification and characterization and
in the biochemical and biophysical techniques used to
study proteins and protein-DNA complexes.
E. Shelden
(SMB): Reorganization of the
cytoskeleton, through the action of proteins affecting
the assembly, disassembly, cross linking and
sequestration of cytoskeletal proteins, is widely
recognized as critical to normal cell division,
development and differentiation, and has been correlated
with changes in cell behavior accompanying abnormal
development or disease progression, such as oncogenesis
and metastasis. We are interested in studying
cytoskeletal and heat shock protein (hsp) regulation
during cellular injury. In particular, we are
studying how hsp27 might stabilize cytoskeletal filaments
in cells during ATP depletion and during exposure to
environmental toxins. Our work is conducted using both in
vitro cell culture models, and in vivo, using the
zebrafish as a model vertebrate system.
M.K. Skinner (SMB): Research in the Skinner laboratory focuses on protein growth factors and how their interactions with specific receptors mediate communication between different cell types in a tissue, as well as on heterodimeric transcription factors that mediate the effects of growth factor recognition on gene expression. The tissues studied are ones important in mammalian reproductive biology: testis, ovary and prostate. Derivatives and analogs of protein growth factors are studied as potential therapeutics. Students in this laboratory will gain wide exposure to current techniques of cell and molecular biology as applied to studies of protein biochemistry.
M.J. Smerdon
(SMB):
Dr. Smerdon has a solid background in physics and
physical biochemistry that he has used to great advantage
in the study of repair of DNA lesions and protein-DNA
interactions involved in the process.
His work has substantial relevance to carcinogenesis and
the action of environmental mutagens and
carcinogens. Trainees with a
background in physical science and an interest in cell
biology would find this laboratory an excellent
choice.
C. Steber
(Crop&Soil Sci.):
An
understanding of the hormonal control of seed dormancy
and germination is critical to the agricultural traits of
preharvest sprouting, seedling emergence, and plant
establishment. We are investigating the hormonal control
of seed dormancy in the model plant Arabidopsis with a
view to applying this knowledge to the crop plant wheat.
Areas of research: 1) Gibberellin signal transduction; 2)
Agricultural traits of preharvest sprouting, seedling
emergence, and plant establishment.
B.J. Van Wie (ChemE): Dr. Van Wie uses ion channel-forming, transmembrane receptor proteins as biosensors for specific antigens. There are currently two major focuses in his laboratory. The first is that of chemical and biochemical sensor for diagnostics and environmental monitoring, particularly on miniature hand-held device technology with telemetry circuitry for water quality testing. The second focus consists of a cross-disciplinary collaboration investigating prophylactic human antibody production and studies of the immune response to biological pathogens. Trainees in this laboratory will receive truly interdisciplinary training involving both chemical engineering and protein biochemistry at the frontline of a rapidly growing field.
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.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.
L. Xun (SMB): The Xun laboratory focuses on two research areas. One is on the enzymology and biochemistry of microbial degradation of chlorinated aromatics and organic chelators, both important environmental pollutants. Studies of dehalogenases that remove chlorine from pentachlorophenol and monooxygenases that cleave NTA and EDTA have provided novel and important information about reaction mechanisms and degradation pathways. The second field of inquiry focuses on how Escherichia coli senses and responds to redox changes. Students in the Xun laboratory receive excellent training in areas of microbiology and protein biochemistry that are relevant to environmental biotechnology.