This is a summary list of all laboratories at Montana State University . The list includes links to more detailed information, which may also be found using the eagle-i search app.
Engineering Mechanics, Continuum and Snow Mechanics
The primary goal of our research is to contribute to a better understanding of why the hippocampus is sensitive to transient cerebral ischemia. During transient cerebral ischemia, intracellular calcium increases initiating a cascade of events which leads to the delayed death of neurons located in the hippocampus.
Our research group is studying the role of calcium targets in mediating hippocampal damage. Behavioral deficits associated with cerebral ischemia in animal models provide a useful tool for understanding the role hippocampus in learning and memory.
Our laboratory uses a variety of behavioral paradigms in conjunction with traditional neuroscience techniques to study how ischemic insult damages the brain.
My laboratory is investigating agent-host interactions in prion diseases, which are fatal neurodegenerative diseases. These are important diseases of humans (Creutzfeldt-Jakob disease), livestock (e.g., scrapie in sheep and bovine spongiform encephalopathy in cattle) and cervids (chronic wasting disease) that have zoonotic potential. Although the majority of prion diseases are due to infection with the prion agent, they can also occur sporadically or as a result of an autosomal dominant mutation in the prion protein gene. The prion agent appears to be devoid of a nucleic acid genome and consists of a misfolded host protein, called PrP-res, that can further induce its own formation from the normal host prion protein. The multiple etiologies of prion diseases and the unusual nature of the infectious agent is novel in microbiology.
Research projects in the Bessen lab include investigations of (1) the routes of prion neuroinvasion following oral exposure; (2) the mechanism of prion agent entry and spread in nerve cells and skeletal muscle; (3) the host physiological responses during chronic wasting disease infection; and (4) transgenic models of CWD pathogenesis. Currently, there are postdoctoral and technical positions as well as graduate student openings available in the laboratory to pursue these studies.
Research in the Bothner lab has two main focuses: (1) understanding the assembly, cell entry, and infection process of icosahedral viruses; (2) Chemical and systems biology approach to cellular stress response. This research takes us from the atomic scale provided by high resolution structural models of virus capsids, to complex interaction networks of nucleic acids, metabolites, and proteins that make up a living system. A diverse set of analytical, biophysical, biochemical, and cell biology techniques are used in the discovery process. The Bothner lab is part of the Center for Bio-Inspired Nanomaterials and the Thermal Biology Institute. Specific research projects include; Metabolomics, proteomics, and transcriptomics of cellular response to viral infection, oxidative stress, and heavy metals. Biophysical analysis of Adeno associated virus cell entry. Mechanism of novel Hepatitis B antiviral compounds.
During embryonic development, cells destined to develop into discrete tissues must recognize and adhere to one another. These adhesive events are mediated by proteins found on the surfaces of cells, an example of which are the cadherins. Cadherins constitute a large family of transmembrane proteins that play essential roles in establishing adherens junctions between neighboring cells. Our lab studies the role of cadherins in embryonic development, with particular emphasis on the formation of the early vertebrate nervous system.
We have isolated several novel cadherin family members from both frog (Xenopus laevis) and chicken embryos. One such molecule, NF-protocadherin (NFPC) is expressed in early embryos in the ectoderm, where it mediates cell adhesion during formation of the embryonic epidermis. NFPC is also found in the developing nervous system in a subset of neurons in both the spinal cord and retina, implying that NFPC might mediate the adhesion and segregation of these neurons during development. We are currently analyzing the function of NFPC in neural tissue, by ectopic expression studies. Results from these studies will provide insights into the molecular mechanisms by which the vertebrate nervous system forms, as well as an understanding of how the adhesion between neighboring cells contributes to cellular differentiation and tissue histogenesis.
Metalloenzymes catalyze remarkably diverse and sometimes extremely difficult reactions in biological systems. The theme of our research is the use of biochemical, spectroscopic, and synthetic approaches to elucidate detailed chemical mechanisms for some of nature?s metal catalysts.
An area of particular interest is the mechanism by which certain metalloenzymes initiate radical catalysis. Metal centers as diverse as binuclear Fe, mono-nuclear Cu, and Co in adenosylcobalamin have been found to play central roles in the generation of catalytically essential radicals. Fe-S clusters have also recently been found to be involved in radical catalysis in a group of S-adenosylmethionine-dependent enzymes. These enzymes are ubiquitious and catalyze a variety of functions, including ribonucleotide reduction, biotin and lipoic acid synthesis, glucose metabolism, and repair of UV-induced DNA damage. The mechanism by which these enzymes initiate radical catalysis is not understood and is a major focus of our research. Our work over the past several years has demonstrated a novel interaction between S-adenosylmethionine (AdoMet) and the enzyme-bound iron-sulfur cluster, in which the AdoMet coordinates a unique iron site of the cluster. We believe this coordination positions AdoMet for reductive cleavage by the cluster, which results in generation of an intermediate 5?-deoxyadenosyl radical.
Another area of interest is the in vivo synthesis of Fe-S clusters. Although such clusters can spontaneously self-assemble in vitro, the conditions under which they do so are far removed from those found in vivo. Evidence points to the involvement of specific metalloenzymes in the biosynthesis of Fe-S clusters, although the mechanism of cluster biosynthesis and its relation to iron homeostasis is not well understood.
Other projects include the investigation of metalloenzymes that quench protein-centered radicals and others that dehalogenate chlorinated organic compounds.
Research interests in our laboratory are in biofilm growth and control in drinking and industrial water systems; the fate, transport and survival of pathogens in biofilm systems; and the physiology of biofilm bacteria. Our focus has been primarily in low-nutrient aquatic environments. We have been using and developing methods for use in environmental systems that include RT-PCR, microarrays, community profile analysis by DGGE, distinguishing live/dead cells by PCR analysis. For determining physiological aspects of biofilm vs. suspended cells, methods development has included microarrays and proteomics, with model organisms being Staphylococcus aureus, Pseudomonas aeruginosa, and Salmonella typhimurium. We also have a focus in integrating information obtained on biofilm formation using the scanning confocal laser microscope with models that can be used to predict biofilm behavior. Recent work also includes investigating the microbial ecology of nitrification in oligotrophic water systems using traditional culturing and molecular methods.
The overarching objective of our research program is to probe key questions in biological chemistry using the tools of the organic chemist. Currently, a major focus of effort in our program is the use of carbohydrate-functionalized dendrimers to study protein-carbohydrate interactions. Dendrimers are ideal frameworks for the study of multivalent protein-carbohydrate interactions because they are three-dimensionally well defined (compared to linear polymers) and are optimally sized for polyvalent binding to lectins. Most lectins have multiple carbohydrate binding sites that are relatively distant from one another (3-7 nm), so a nanometer-sized framework is required if more than one binding site per lectin is to be targeted.
One major area of emphasis for this research is the study the role of protein-carbohydrate interactions in cancer metastasis. Many reports suggest that cell surface carbohydrates serve a critical function in malignant transformation and metastasis, and so the development of artificial carbohydrate arrays that can aptly mimic and interfere with metastasis is also critical. Our goal is to advance fundamental knowledge regarding the role of protein-carbohydrate and carbohydrate-carbohydrate interactions in the metastatic spread of cancer. Concurrently, new therapeutic agents to arrest cancer metastasis may also emerge.
Magnetic Resonance Imaging (MRI) is a noninvasive experimental technique which has found broad application in clinical medicine and is a maturing method for studies in engineering and physics. Our group uses instruments that allow MRI to be applied with a resolution of 10 um over 10 mm diameter samples. MRI applied on this scale requires more sample specific tailoring of the pulse sequences and is more often termed Magnetic Resonance Microscopy (MRM) to distinguish it from medical scale imaging.
Our work is concerned with furthering application of MRM methods in the study of transport phenomena and material characterization. We use pulsed gradient spin echo (PGSE) techniques to measure velocity and effective diffusion, e.g. dispersion. The ability to spatially resolve velocity and diffusion fields allows for transport visualization. Application of PGSE methods without spatial resolution provide the scale dependent statistics of motion over the entire sample, rendering it a powerful technique for studying anomalous transport phenomena. The research program seeks to both elucidate new transport phenomena in complex systems and develop MRM methods for new applications.
Dr. Colclough’s research centers on generational and cultural differences in end-of-life decision making, especially minority population in particular Japanese Americans and American Indians. More broadly, her interest includes nursing ethics, qualitative method, a community-based participatory research approach, and gerontology.
Our laboratory specializes in nuclear magnetic resonance (NMR)-based structural biology research. We are particularly interested in understanding the crucial links between the molecular structures, internal dynamics, and biochemical functions of proteins that are of importance to human endeavors. Questions of interest are: What is the connection between a protein's three-dimensional architecture, flexibility of its amino acids and of its structural elements, and its biological function(s)? How do atomic structures and internal dynamics modulate the biochemical activity of proteins? What is the significance of conserved amino acid residues in protein families? Our approach to providing answers to these scientific issues is to use modern multidimensional (2D, 3D, 4D), heteronuclear (1H, 15N, 13C, 2H) solution nuclear magnetic resonance (NMR) spectroscopy in conjunction with complementary biophysical techniques. We are currently investigating the structural and functional properties of several intriguing proteins.
Our laboratory is focused on elucidating pathogenesis mechanisms of the human fungal pathogen Aspergillus fumigatus (Af).
Research interests in the Dlakic lab include: Ribosome synthesis in budding yeast; Protein evolution and 3D modeling of proteins; Structural polymorphism of DNA; Comparative genomics
We are a diverse group with expertise in biochemistry, molecular biology, physics and chemistry, with a wide array of interdisciplinary research interests including:
* Advanced materials for energy
* Biomedical nanotechnology
* Hierarchical assembly
* Nanoparticle growth processes
* Complex chemical networks
The Dratz lab studies the structure and function of membrane receptor and amplifier proteins and uses global proteomic analysis to study signaling networks in cells. The mechanism of conversion of light to electrical signals in vision is of long-standing interest and is an archetype G protein-coupled receptor (GPCR) system that is responsible for over half the signaling systems in biology. Chemokine GPCRs that are responsible for intercellular signaling in the immune system are also used as receptors for virus entry. We are studying agonist and antagonist binding mechanisms in two chemokine receptors CCR5 and CXCR4 that AIDS virus uses to gain entry to lyphocytes and where infection is blocked by agonists and antagonists. Approaches include antibody imprinting for protein structure determination, development and application of new methods for global proteomics analysis, photochemical cross-linking of bioactive molecules to map out receptor binding sites, and protein and peptide mass spectrometry. In collaboration with Prof. Grieco's group we are developing new fluorescent dyes for ultrasensitive detection in proteomics and applying this technology for example, to new finding new diagnostic tools, to increased understanding of immune adjuvants and to understanding neurodevelopment. Prof. Dratz has a long standing interest in biochemical nutrition and is applying proteomic methods to gain deeper understanding of nutritional issues in collaboration with groups in Plant Sciences and Health and Human Nutrition.
We are interested in environmental signals that are sensed by cells to mediate control over physiology and modes of growth. In particular, we are interested in the genes used to sense environmental changes in response to biotic and abiotic parameters, and how microibal cells respond in order to optimize metabolism. We study both monocultures and indigenous microbial communities to better understand the interrelationships between genomic content and phenotype at different levels of resolution (i.e., DNA to communinty), and how these attributes contribute to stress and survival of biological cells. Within the contexts of cellular responses, we study bacterial systems important for heavy metal biormediation, metal corrosion, extemophilic lifestyles, and bio-energy.
- Studies of deep ice cores from the Arctic and Antarctic
- Environmental Biofilms
- Dissolved organic matter (DOM) dynamics
The Franklin lab has three primary areas of research regarding the activity of the oppportunistic pathogen Pseudomonas aeruginosa.
(I) Biosynthesis of the protective capsular polysaccharide.
(II) Spatial and Temporal aspects of gene expression in P. aeruginosa biofilms.
(III) Interactions of P. aeruginosa with the innate immune response.
Our research focuses on interactions between microorganisms and minerals. We are studying the behavior of the disimilatory iron reducing bacterium Shewanella oneidensis MR-1 during respiration on hematite, a crystalline iron oxide that serves as a terminal electron acceptor for this bacterium. This research is undertaken as a collaboration with scientists at the Pacific Northwest National Laboratory and the University of Guelph in Ontario, Canada. Our group is also studying how methyl mercury is produced in geothermal food webs of acidic environments in Yellowstone National Park and how organisms at different trophic levels have adapted to elevated methyl mercury concentrations during their evolution. This work is conducted in collaboration with Professor Tamar Barkay at Rutgers University, Professor Jeff Tomberlein at Texas A&M University and Kirk Nordstrom at the USGS in Boulder, Colorado.
Research in this lab combines expertise in hydrodynamics, geochemistry, microbial ecology, biochemistry and genomics leading to a better understanding of the interface between the biosphere and geosphere.
Subsurface Biofilm Barriers can be used to manipulate the hydraulic conductivity (permeability) of subsurface formations enabling us to decrease or direct the flow of groundwater. Subsurface biofilm barriers are also being developed for increased storage security during geologic carbon sequestration.
By improving our ability to transport bacteria and nutrients in the subsurface and designing biofilm barriers to be reactive (e.g. contaminant degrading) or non-reactive (simply for hydraulic control) we are intending to improve existing subsurface bioremediation technologies.
We are investigating the transformation of nitroaromatics (e.g. the explosive TNT - 2,4,6-trinitrotoluene), chlorinated aliphatic compounds (e.g. trichloroethylene - TCE and carbon tetrachloride - CT), heavy metals (e.g. chromate and dichromate), and radionuclides (e.g. uranium and strontium). The influence of natural organic matter, minerals, and co-contaminants is of specific interest to my research as well as the establishment of biogeochemical conditions (pH, redox potential, oxygen concentration, etc.) ideal for the safe removal of these contaminants from contaminated groundwater or immobilization in contaminated soils.
Lastly, the development of algae based technologies for liquid transportation fuel and other high value product generation is being investigated.
Neurophysiology of Visual Perception and Cognition
In my laboratory, we study the neural processes that underlie visual perception and cognition. We use electrophysiological methods to measure neuronal activity in the cerebral cortex and study the relationships between that activity and visually guided behavior.
Virus-host cell interactions and consequent gene regulation
The Hardy laboratory studies interactions between enteric viruses and host cells at the molecular level. We seek to understand how protein-protein interaction networks regulate both viral gene expression and the host cell genetic response to virus invasion. Research in the lab focuses on the rotaviruses, the most important cause of pediatric diarrhea worldwide. Current projects in the lab include molecular and proteomic investigations of how rotaviruses modulate cellular antiviral gene expression, and mechanisms of innate immunity to viral infection.
Research in the Harmsen Lab encompasses the areas of Pulmonary Immunology and Immunopathology. The lung is extremely susceptible to infection because of the constant deposition of potential pathogens in the airways that results from breathing contaminated air. Thus, the lung must respond to these pathogens quickly and intensely to avoid infection. Although these host immune and inflammatory responses usually are successful in preventing infection, these processes can also be damaging to the host. This is especially a problem for the lung because the delicate lace-like structure of lung tissue is easily damaged. In addition, misguided immune responses to inhaled noninfectious antigens, such as allergens, can directly cause serious diseases such as asthma and bronchitis. The major goal of our research is to better understand how the lung immune responses can resist infections and yet limit "collateral" host damage caused by the immune response. In the process of studying these mechanisms of resistance and tissue damage, our lab utilizes animal models of disease. These include mouse models of influenza, Pneumocystis murina pneumonia, Coxiella burnetii, and Streptococcus as well as bovine models of viral and bacterial pneumonia.
Dr. Holkup’s research interests relate to Native American elder abuse, which is a hidden health disparity in tribal communities as well as a nexus for other better-known disparities. The Caring for Native American Elders project uses a community-based participatory research approach to study elder abuse and to offer a culturally anchored family conference intervention to address this complex and sensitive concern.
Our laboratory creates new, genetically encoded fluorescent
biosensors to solve fundamental problems in neuroscience.
We currently have two research goals in the laboratory that address fundamental problems in neurobiology.
Fluorescent biosensors for optically recording from excitable cells.
Advances in electronics and neurobiology have made it possible record from excitable cells such as the neurons of the brain. It is now common place for the neuroscientist to record from a neuron and to understand when it responds in relation to a particular stimulus or before a movement. This has produced tremendous advances in neuroscience, in our understanding of the brain, but we are only listening to one, or a few, neurons at a time. Even simple nervous systems involve hundreds of cells and thousands of connections, and we need to understand how the entire circuit works. One way of doing this involves electrically recording from many different neurons at the same time. Our colleague Charles Gray is pioneering new ways of recording from many neurons at the same time. In our lab we are trying to create new generations of genetically encoded fluorescent proteins that will signal voltage changes when a neuron fires. This is work that we are doing with our collaborator, Ehud Isacoff at UC Berkeley. Put simply, we are trying to fuse jellyfish fluorescent proteins to voltage-gated ion channels to produce a biosensor that we can then express in the nervous system so that neuroscientists can optically record the activity of entire neural networks.
Looking at intracellular signaling
There are many signaling pathways in cells beyond simple changes in voltage. Proteins talk with one another to regulate excitability, gene expression, and even the decision of whether to live or die. We are currently developing new fluorescent methods for watching these protein interactions in real time and in living cells. This work involves fusing two different fluorescent proteins to a signaling protein such that we create a FRET based biosensor. This sort of work is producing new ways of measuring intracellular signaling, and it is our hope that some of the biosensors will speed up the process of searching for new, important drugs.
The Jacobs Lab research and scholarship efforts fall into 4 different areas: 1) basic neuroscience research on sensory processing, 2) basic and applied research on informatics and data sharing techniques for the neuroscience community, 3) implementation of IT-based infrastructure for the science and education communities and 4) science pedagogy.
* Interactions of N-formyl Peptide
* Regulatory Interactions of N-formyl Peptide
* Reorganization of the Plasma Membrane
* Random Sequence Phage Display Analysis
* Immunocytochemical Detection of Lipid Peroxidation
* Structural and Function Analysis of the Superoxide
Inflammatory disease and developmental immunology. My laboratory studies the molecular events that control leukocyte entry into sites of acute and chronic inflammation. Analyses of gamma/delta T cells are also pursued in the context of host immune responses and developmental immunology.
My interests lie in describing and modeling the physical, chemical, and biological processes that are important in sessile microbial community ecology. Long term aims include developing modeling techniques needed to connect bioﬁlm models to real world microbial communities and to use bioﬁlm modeling methods to help further develop theory for microbial communities, especially description and prediction of niche structure based on the physico-chemical environment.
Knighton Group Overview
Dr. Knighton has been actively involved in the development and application of chemical ionization mass spectrometry for nearly 20 years. That interest continues today and is primarily focused on using drift tube reaction mass spectrometry for the quantification of trace level volatile organic compound (VOC) emissions from a wide variety of natural and anthropogenic sources. A significant fraction of this research effort involves field work where a proton transfer mass spectrometer (PTR-MS), a commercially produced drift tube reaction mass spectrometer, has been used to measure selected volatile organic trace gases in the ambient atmosphere and in the emissions from vehicles and aircraft. The PTR-MS instrument merges the concept of chemical ionization with that of the swarm technique of flow-drift tubes. Chemical ionization is based on H3O+ as the primary reagent ion, which does not react with the major components of clean air, but does react with most non-alkane VOC's via proton transfer reactions. The electric field used to transport the ions through the drift tube also provides sufficient additional energy to the ions to discourage association reactions with water molecules that are always present in any real sample. The selectivity provided by chemical ionization, control of unwanted hyfration reactions by using drift tube coupled with the sensitivity of mass spectrometry detection makes the PTR-MS a powerful analytical tool capable of rapid in-situ measurement of trace chemical species with proton affinities greater than that of water. Because the PTR-MS provides sensitive (sub-ppbv) real-time (~1 second) measurement of selected hydrocarbon components, it is ideally suited for monitoring systems that have rapidly changing chemical composition like that of engine exhaust emissions. The MSU PTR-MS system has been deployed in a wide variety of field programs including the measurement of aerosol trace gas precursor species in jet engine exhaust in the Aircraft Particle Emissions eXperiment (APEX)-2004, APEX2-2005 and APEX3-2005, on-board the Aerodyne Mobile Laboratory for the measurement of selected VOC's in Mexico City Urban Air Quality field measurement campaigns of 2002, 2003 and 2006. In addition, we have used the PTR-MS technique in the study of a diverse set of matrices including the monitoring of flavor compounds in human breath, volatile emission products of an endophytic fungus, Muscodor Albus, and those released from softwood lumber during the kiln drying process.
Knighton Research Projects
To continue to refine and improve drift tube reaction mass spectrometry for the analysis of selected hydrocarbons in challenging measurement environments. The analysis of complex mixtures directly by chemical ionization spectrometry techniques like the PTR-MS is often complicated by ion fragmentation and ionization of interfering compounds. Two important air toxic compounds 1,3-butadiene and acrolein are listed as emission components in aircraft exhaust. Presently there are no existing technologies capable of reliably measuring these components in aircraft exhaust. Knowledge about the emissions of compounds from aircraft is important towards understanding the influence that commercial aircraft may have on human health. While the PTR-MS provides a response to both 1,3-butadiene and acrolein, interferences from other aircraft exhaust compounds notably water and the isomeric butenes makes the direct analysis of these componenets impossible. Funding from NSF and FAA is being used to work on a series of techniques to allow for the analysis of these compounds. These include: 1) Designing simple chemical scrubbers that selectively remove interfering compounds so that traditional PTR-MS techniques can be employed. 2) Discovering and learning how to produce new reagent ions that react selectively with either 1,3-butadiene and acrolein but not the other interfering compounds. 3) Develop MS/MS methods using a newly built triple quadrupole drift tube reaction mass spectrometer. The first study envisioned for this instrument is to use MS/MS to resolve mixtures of protonated acrolein C3H4OH+ and protonated butene C4H8H+.
We are involved in structural studies on many fronts using X-ray crystallography as our primary tool. These studies are in many cases collaborations with others, both on campus and off. Focal areas include: 1) Structural biology of iron transport, iron homeostasis and oxidative stress. 2) Strutural studies of hyperthermophilic viruses. 3)Structural studies of the prokaryotic adaptive immune system.
Our lab investigates the cellular and molecular mechanisms that drive the formation of the nervous system. Specifically we are interested in how extracellular signals located in the environment integrate with intrinsic cellular cues to regulate the migration, proliferation and differentiation of the cell types that comprise the peripheral nervous system (PNS). We focus on the peripheral nervous system because it is generated by a fascinating, heterogeneous population of precursor cells called the neural crest, that migrate widely throughout the embryo, stop in stereotyped locations and differentiate into a plethora of critical cell types including sensory and sympathetic neurons.
Research in the Lei Lab focuses on pathogenic and therapeutic studies relating to the bacterial pathogens Streptococcus pyogenes and Streptococcus equi.
Dr. McDermott teaches undergraduate and graduate courses in Soil & Environmental Microbiology. His microbial ecophysiology research focuses primarily on the following topics:
1) Microbe-metalloid interactions.
2) Chemolithotrophic thermophilic microorganisms in Yellowstone National Park.
3) Thermoacidophilic eukaryotic algae inhabiting acidic hot springs."
Research in the Meissner-Pearson lab focuses on the interaction of immune signaling pathways and their impact on haematopoietic stem cell differentiation and apoptosis.
The lab studies the molecular mechanisms that underlie patterning of the vertebrate nervous system during embryonic development. Our lab focuses on how the early neural plate is subdivided into the different regions of the brain. We use the frog Xenopus and the chick as model organisms.
Research in our lab is directed toward understanding the function of two neutrophil receptors, the formyl peptide receptor (FPR) and the C5a receptor (C5aR), which play a central role in inflammation. Ligand binding to these receptors leads to important host defense functions such as killing of microorganisms. Unfortunately, neutrophils are also involved in the pathology of various inflammatory conditions. Our goal is to learn more about neutrophil activation by studying the functions of FPR and C5aR.
My recent experimental and theoretical studies have been focused on an analysis of the "codes" with which nerve cells in sensory systems represent information about external stimuli, the neural mechanisms through which that information is processed within subsequent stages of the nervous system, and the extent to which the nervous system may have become optimized through evolution.
My recent experimental and theoretical studies have been focused on an analysis of neural coding in the cricket cercal sensory system. The general problem has been broken down into several distinct questions related to aspects of the observed stimulus/response characteristics of the neurons: 1) What parameters of sensory stimuli are encoded in the spike trains of the receptors and first order sensory interneurons in this system? 2) What is the theoretical limiting accuracy with which those parameters could be decoded from the neuronal spike trains? 3) How is the information encoded within different aspects of the spike train patterns? 4) What are the structural and biophysical mechanisms through which the observed coding scheme is implemented within this neural network?
In collaboration with Dr. Tomas Gedeon in the Department of Mathematical Sciences, I am also studying the extent to which the structure and function of the cricket cercal sensory system may have been optimized, through evolution, to be more efficient from the standpoints of neural computation and sensitivity.
My general approach is to integrate electrophysiological experimental recording techniques with advanced mathematical analysis techniques toward a rigorous characterization of the neural encoding schemes. Electrophysiological approaches techniques include intracellular microelectrode recording and multi-unit extracellular recording. The major analytical techniques I have used include compartmental modeling of single identified nerve cells and a branch of multivariate statistics called "information theory."
The Obar Lab is actively investigating the role of mast cells during influenza A virus infection and the mechanisms contributing to differentiation and maintenance of protective memory CD8+ T cells.
Attenuated Salmonella vectors, adept at delivering vaccines to the PPs, elicit T helper (Th) 1 cell (IFN-γ-dependent) immune responses to resolve its infection. However, our studies show that we can obtain elevated Th2 cell (IL-4-dependent) immune responses, followed by a delayed onset of Th1 cells to colonization factor antigen I (CFA/I), from human enterotoxigenic Escherichia coli (ETEC). Subsequent studies revealed that proinflammatory cytokine production are abated suggesting this acts as an anti-inflammatory vaccine. Current studies are evaluating the efficacy of this vaccine against autoimmune diseases such as experimental autoimmune encephalomyelitis (EAE) and collagen-induced arthritis. Our recent findings show that this vaccine induces regulatory T cells, but the type of regulatory cell induced is disease-dependent. We are currently investigating how Salmonella-CFA/I stimulates the production of these regulatory T cells, and we are determining the involved dendritic cells that sustain these responses.
Effective treatments for multiple sclerosis (MS) are problematic due to its unknown etiology. Current work has adapted the rodent EAE model to test whether our tolerogen vaccine delivery platform, the reovirus adhesin, protein sigma 1 (pσ1), can improve mucosal auto-antigen uptake. We show that a single low-dose of pσ1-based vaccines induces tolerance and prevents or treats autoimmunity when applied mucosally. Our studies show that pσ1-mediated tolerance is IL-10-dependent via regulatory T cells. In addition, regulatory elements with the IL-4-producing CD25- CD4+ T cells have been found. Further work will determine the mechanisms used by pσ1 and to understand the involved dendritic cell subset(s) that stimulate regulatory T cells. Ultimately, these studies will determine the feasibility of using pσ1-based single-dose delivery system to prevent and/or treat autoimmune diseases.
One goal of our work is to improve and devise novel vaccine delivery systems by taking advantage of infectious agents' adhesins, particularly those that can target mucosal inductive tissues for the GI and respiratory tracts. We employ three vaccine delivery systems: the nonreplicating adenoviral vector for delivery into respiratory tissues, live attenuated Salmonella for delivery into the GI tract, and DNA formulations for both the respiratory and the GI tracts. The objectives for our studies include 1) to delineate the immune T and B cell responses to the vaccine; 2) to assess the type of CD4+ T cells elicited; and 3) to design vaccines to produce the desired T cell response. We are currently evaluating vaccine candidates for ETEC, Coxiella burnetii, Brucella, botulinum, and Yersinia pestis. The results of these research endeavors will ultimately have clinical, veterinary, and wildlife applications.
Biochemical and physical approaches are used to examine the structure and mechanism of complex iron-sulfur enzymes including nitrogenases, hydrogenases, and radical SAM enzymes.
The long-term goal of my research program is to understand the molecular basis of leukocyte superoxide (O2-) production and the role of leukocyte-generated oxidants in the tissue damage associated with inflammatory diseases in animals. Because of the importance of leukocytes in host defense and in inflammatory diseases, the research in my lab is focused on four primary approaches to understanding the biochemistry and molecular biology of the NADPH oxidase and the role of leukocyte-derived oxidants in tissue injury. These approaches include: 1) analysis of the human and bovine neutrophil NADPH oxidase to determine the protein and lipid components involved and how these components assemble with each other at the molecular level; 2) biochemical and molecular biological analysis of the proteins known to be involved in the NADPH oxidase to determine their molecular structure and functional role in enzymatic activity; 3) functional analysis of the NADPH oxidase to determine how this system is regulated and what causes this system to become deregulated during disease states; and 4) analysis of inflamed tissues for markers of oxidant injury.
Organic synthesis has developed over the past 180 years to the extent that few organic compounds lie outside the realm of feasible construction. Despite such advances, the inability of chemical synthesis to construct molecules of even moderate complexity in a practical sense both reflects deficiencies in our understanding of chemical reactivity as well as serves to illustrate the need for new reaction development.
Towards redressing these shortcomings, I intend to initiate a research program that will focus foremost on the synthesis of architecturally interesting, biologically active compounds, with a strong emphasis on the development of novel reaction methodologies of general utility. In effect, natural product targets will serve as focal points for the development of new reactions, strategies, and stereoselective methods."
These goals will be initially pursued in the context of the natural products actinophyllic acid; the daphnicyclidin family of alkaloids; and the azatricyclic core of madangamine F.
A team of us is developing new crops that are, due to our efforts, in increasing acreage in Montana. The approach focusses on providing consumers with foods that meet the their nutritional needs, especially those needs of specially challenged consumer groups (diabetes, depression, obesity, gluten intolerance, athletes and vegetarians). Our work is based on coupling human inherited disease genetic information, with plant genetics and with rural cooperatives. A paper outlining the need for a recommitment of agriculture to human nutrition, has been published in September 2006, in Nature Biotechnology. Objective: develop on average one new nutrition based crop worth $50 million/year for Montana. So far so good. To date we have developed gluten-free Montina, Timtana, and Proatina for people who suffer from wheat intolerance, and a wrinkled pea for diabetes type II. We also work on Camelina , a new crop that is high in omega-3 oil, hence good for human nutrition. Additionally we work with a plant-associated bacterium that nucleates ice formation, as it may be important in nucleating rainfall. We have also developed a lysine excreting bacterium for bread fermentation in Africa where lysine is inadequate in cereal based diets. We also work on using novel genetic selection methods for microbes to control weeds, including Striga, the worst weed in Africa.
The lab's primary research interests are to understand the intricate gene regulatory mechanisms that function in development and maintenance of complex organisms, like ourselves.
Application of Magnetic Resonance Microscopy (MRM) methods in the study of transport phenomena and material characterization.
Research in the Sharrock laboratory focuses on two areas of plant molecular genetics: the mechanisms through which plants sense and respond to environmental light cues and the regulation of the development of the floral stem or inflorescence. For the first of these research areas, our overall objective is to understand how the phytochrome red/far-red photoreceptors trigger and coordinate plant developmental responses to the light environment. This work has employed molecular and genetic approaches to define the structures of the five Arabidopsis phytochromes, the physiological and developmental roles of these receptors, and their patterns of expression in the plant. Future research directions focus on early events in phytochrome activation and identification of components of the signal transduction pathways through which phytochromes modulate growth and developmental responses.
The second major focus of the lab is isolation of mutants that alter the growth and structure of the Arabidopsis flowering bolt, or inflorescence, and the identification of the genes that correspond to these mutations. Ultimately, our objective is to describe molecular pathways in plants that control internode elongation in the inflorescence stem and, therefore, determine critical aspects of plant reproductive architecture and adaptation.
A central theme of the research in our laboratory is the development of new methods and instrumentation in magnetic resonance spectroscopy targeted toward the elucidation of molecular structure and chemical dynamics in complex materials containing both electron and nuclear spins. Two broad areas of application dominate our research: the characterization of novel optical materials; and structural biology of proteins with metal and free radical centers - with a particular emphasis on the biochemistry of NO.
In the first application, we use magnetic resonance techniques to analyze the composition of new solid-state laser materials - primarily materials under development by local optics industry. Our approximate goal is to determine the identity, oxidation state, and incorporation sites of transition metal ion guests and defects in the materials. Our results provide a basis for refining synthesis techniques and for developing leads for new types of laser materials. On a fundamental level, we are studying the electron-transfer chemistry that occurs among redox active metal ions in insulators, with the goal of exploiting this chemistry to develop new materials with photon-modulated optical properties.
In pursuit of these goals, we have recently installed a novel, 95 GHz electron paramagnetic resonance (EPR) spectrometer, It is the only high-frequency EPR instrument in the west, and is arguably the most advanced and versatile of all instruments currently in operation in the United States. A key feature of this instrument is its capabilty for characterizing inherently small samples, such as optical fibers.
The second area embraces our long-term goal of establishing methods for the site-selective structural characterization of large, biological molecules. This work has featured studies of the catalytic active site in the G-protein, ras p21, by means electron-spin echo envelope modulation (ESEEM), and high-frequency EPR spectroscopy. Recently, we have initiated site-directed spin labeling (SDSL) of the ligand binding site in the formyl-peptide G-protein coupled receptor of human neutrophils. In our high-frequency EPR instrument, spin-label EPR experiments are feasible with as little as 10 picomoles of sample - a hundred-fold reduction as compared to conventional instruments.
A major thrust of our biophysical research involves the biological activity of NO. The production of nitric oxide is linked to a diverse set of biological activities, which span vascular, pulmonary, neural, and immunological domains, and intriguingly embrace both toxic and salutary effects. Our research in this area is focussed on the interplay between metal-centers and thiol effectors in evoking the biological activity of NO.
It has recently been discovered that human hemoglobin undergoes nitrosylation in vivo at both heme-iron and thiol (Cys93 in the ÃŸ-subunits) groups. Moreover, there appears to be a mutual allosteric modulation of dioxygen binding to the heme, and NO-group displacement from heme to thiol. This chemistry is conjectured to play a key role in regulation blood pressure and flow. Our group is using EPR spectroscopy in combination with other spectroscopic techniques - including UV/VIS, IR, and resonance Raman - to test and refine emerging models of the chemical dynamics of NO-hemoglobin interactions.
Research in the Skidmore Lab is focused on Biogeochemistry and Geomicrobiology
There are two main areas of research being conducted in the Spangler group. The first involves investigation of optical materials and the mechanisms by which they function. In materials such as laser materials, optical power limiters (materials with non-linear absorption which can protect against lasers) and photorefractives, complicated energy transfer and charge transfer processes can occur after the initial photoexcitation. These processes can occur on timescales ranging from 10-13 sec to minutes and can cause spectral changes anywhere in the optical range (UV to IR). For this reason, we are developing new, multi-dimensional spectroscopic techniques for the investigation of optical materials that yield high information content in a relatively short experiment time.
Dr. Stewart’s research focuses on the control of detrimental microbial biofilms. Biofilms are slimy, multicellular aggregates of bacteria or yeast that form on wetted surfaces. The persistent infections associated with catheters, heart valves, periodontitis (gum disease) and burn wounds are examples of biofilms that affect human health. When microorganisms group together in biofilms they evade killing by antimicrobial agents (disinfectants, antibiotics) that easily kill their free-floating counterparts. Dr. Stewart is interested in the mechanisms that protect microbes in biofilms. These include poor penetration of antimicrobial agents, variation in the physiological activity of microorganisms with biofilms, phenotypic variation, and the activation of stress responses. Dr. Stewart has also investigated alternative strategies for controlling biofilms including anti-biofilm coatings, chemical or enzymatic degradation of the matrix holding the biofilm together, and disruption of cell-to-cell communication.
My lab studies somatosensory neural circuit organization and information processing in Drosophila using optogenetic approaches. How sensory information is processed by the nervous system to produce behavioral outputs is a long-standing problem in neuroscience, but one far from being understood. My lab exploits the many advantages of the Drosophila model system to study the relationship between somatosensory input and behavior. Our overall strategy is to first map neural circuits associated with specific somatosensory neurons and then manipulate and measure neuronal activity within the circuit to elucidate the fundamental principles of neuronal circuit logic.
Since the depth with which a neural circuit will be understood will correlate with the precision with which it can be manipulated, we are generating fly strains containing enhancers specific for sensory neurons, each type of neurotransmitter, and each type of neurotransmitter receptor. These valuable tools will allow us to express transgenes for manipulating and measuring neuronal activity in small subsets of neurons in an intact animal. Connections between neurons are being mapped using a recently developed method in which Green Fluorescent Protein (GFP) is split in two and its separate parts expressed independently in neuronal subsets using these specific enhancers. Synaptic connections between specific neurons are confirmed where GFP is functionally "reconstituted" and observed as green fluorescence. These same enhancers are being used to drive expression of excitatory and inhibitory light-gated ion channels in small subsets of neurons. Expression of the excitatory channel Channelrhodopsin2 in sensory neuron subsets allows larval behavior to be controlled with light. As enhancers that allow expression in neurons downstream of the sensory neurons are generated, expression of the excitatory and inhibitory light-gated channels will enable a determination of neurons that are necessary and sufficient to trigger given behavioral responses. As a given neural circuit becomes more defined, neuronal subset-specific enhancers will be used yet again to express genetically-encoded calcium indicators to allow optical measurements of neuronal activity. Longer term, once multiple neural circuits are mapped, studies will be initiated to work out how distinct neural circuits compete with, enhance, or otherwise interact with each other as this is more realistic approximation of what occurs in natural world.
My research interest covers three highly interdisciplinary fields of chemistry: bioinorganic structure and reactivity, computational method development, and physical organometallic chemistry and catalysis. A key aspect of my research philosophy is the close correlation of experiment and theory. I use spectroscopic techniques (mainly near-edge X-ray absorption spectroscopy (XAS) and Extended X-ray Absorption Fine Structure (EXAFS) to directly probe electronic and geometric structures of inorganic and bioinorganic systems. These XAS measurements are carried out at the beamlines of Stanford Synchrotron Radiation Laboratory, Menlo Park, CA and Advanced Light Source, Berkeley, CA. In addition, I employ a broad range of computational chemical methods, including forcefields, semi-empirical Hamiltonians, ab initio molecular orbital and density functional calculations to support and interpret experimental findings.
Design of an effective vaccine against HIV must take into account the high degree of variability in the sequence of the envelope proteins that has been observed in clinical isolates, and the high mutation rate of the virus. Vaccines based on the envelope glycoprotein gp120 have been ineffective in protecting against clinical isolates of HIV. Most of the antibodies that are elicited are directed against variable portions of the sequence. Some HIV-infected patients, however, develop neutralizing antibodies with broader strain specificity, many of which appear to be directed at the three- dimensional shape of the CD4 binding site on gp120. This part of the molecule is conserved in structure, because all HIV use the CD4 receptor to gain entry into the cell. Our hypothesis is that this part of gp120 will make a more effective vaccine antigen than the whole protein. We are therefore constructing recombinant or synthetic molecules that display this conformation-dependent structure. We have identified peptide structures that can mimic the sites recognized by some of the neutralizing antibodies using phage-display technology and are displaying these peptides on the surface of other viruses or nanoparticles, and using them to immunize mice and rabbits. We are also taking the synthetic peptide sequences and determining their three-dimensional structures when bound to the antibodies. The information obtained from X-ray crystallography of the peptide-antibody complexes will be used to design better antigens that can elicit a more effective immune response to the virus. Comparing the structures of different antibodies to the CD4 binding site that vary significantly in their ability to neutralize primary HIV strains will also shed light on what determines their potency.
Blocking The Interaction Between the HIV Envelope Protein and the Chemokine Receptors CCR5 and CXCR4:
This project aims to determine the structure of the CCR5 and CXCR4 chemokine receptors at their ligand binding sites and their interaction with agonist and antagonist molecules. CCR5 is the co-receptor required for infection by primary isolates of HIV (the M-tropic/R5 strains predominantly transmitted between people) and CXCR4 is used by the X4 strains that predominate at later stages. The goals of the project are to: (1) Synthesize photo-activatable analogs of peptide and non-peptide antagonists that block HIV infection. (2) Photo-crosslink bioactive analogs to CCR5 or CXCR4, and locate crosslinking sites using mass spectrometry (LC/MS/MS) to map the antagonist binding pocket in the receptor. (3) Map the structure of the HIV/chemokine binding pocket by scanning photoactivatable amino acid analogs over chemokine peptide agonist sequences, photocrosslinking the bioactive analogs to the receptors, and using MS to determine residues lining the binding sites. The ultimate goal is to provide a foundation for more effective structure-based design of HIV entry inhibitors.
Design of small-molecule CXCR4 antagonists for HIV and cancer treatment
We are designing and synthesizing non-peptide small molecule inhibitors of CXCR4. Lead compounds that compete with known CXCR4 antagonists, such as the peptide T-140, are being tested for their ability to inhibit HIV infection in vitro, and to inhibit tumor cell metastasis in vitro and in vivo.
The long-term objective of our research is to define the influence of sensory/regulatory systems on Staphylococcus aureus (S. aureus) virulence using clinically relevant strains. Relatively little is known about how pathogens detect components of the human innate immune system to respond and survive within the host. National Institutes of Health (NIH) funded projects in our laboratory investigate molecular mechanisms used by S. aureus to avert destruction by the human innate immune system at the host-pathogen interface during bacteremia and skin infections. Additional NIH funded projects include investigating the characteristics and incidence of methicillin-resistant S. aureus nasal colonization in minority populations. Our lab is also funded by the United States Department of Agriculture (USDA). For our USDA projects we investigate incidence and characteristics of S. aureus in Montana’s dairy herds and study the antimicrobial potential of a chemokine found in bovine milk. We have also started to determine the zoonotic potential of S. aureus and are focusing on the incidence and transmission potential of S. aureus in Montana’s equine populations.
Our group develops and utilizes optical methods to study chemical structure, organization and reactivity at surfaces. While the systems studied are diverse and far ranging, our goal is always the same: we work hard to understand how asymmetric forces found at surfaces alter interfacial chemistry from bulk material limits. Projects currently underway fall into two general categories: 1) solvation at liquid surfaces and 2) high temperature surface chemistry in electrochemical devices.
The Ward lab primarily studies cyanobacterial mat communities common in alkaline siliceous hot springs in Yellowstone National Park.
The Ward lab is also focused on understanding the relationship between mat cell component biomarkers and the community members that contribute them to mats build by cyanobacteria and anoxygenic phototrophs. The goal is to understand how biomarkers and isotopic signatures in fossilized mats (stromatolites) should be interpreted.
My program is focused on the use of viruses as genetic and molecular tools for fundamental discovery. By combining biochemical and genetic approaches, with the tools of molecular and structural biology. I examine the interplay of viral and host gene products and mechanisms of viral assembly and disassembly. The principle areas of research currently under investigation include:
1. The use of viral protein cages as constrained reaction vessels for nano-materials synthesis with applications in medicine and material sciences.
2. The isolation and genetic characterization of novel viruses from extreme thermal environments found in Yellowstone National Park and other thermal regions worldwide.
Found 59 laboratories .