Grant #P20RR016454 
 funded by
NIH  NCRR


 

Boise State University and the Boise VA Medical Center Prospective Mentors

 

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Dr. Tim Anderson

Boise State University

Computer Science

tim@cs.boisestate.ed

http://cs.boisestate.edu/~tim/

 

 

Research:

 

I am conducting research in the following areas:

 

Biologically Inspired Computing: improved methods of computation based on principles derived from biological systems.

 

Artificial Neural Networks: develop artificial systems that exhibit brain-like capabilities of learning and self adaptation by simulating the basic structures found in the human brain, such as neurons and synapses.

 

Genetic Algorithms: A biologically inspired search technique that has proven successful on difficult optimization problems.

 

Document Recognition and Analysis: This involves segmentation and labelling of regions of interest in a document, optical character recognition, noise removal, etc.

 

DNA sequence analysis: Discovering and characterizing interesting sequences/patterns in DNA.

 

Summer Project:

 

     I am working with Dr. Greg Hampikian on a DNA sequence analysis project.  Our goal is to identify and characterize short sequences that *do not* exist in the published Human (and other organisms) DNA sequence.  In addition to discovering and characterizing these sequences, we will also be interested in discovering and characterizing other interesting patterns.  There are a number of things that a student could work on in this area.  One of our primary needs is a student who can write scripts and programs to automate the search for these sequences.  Much of this work will be done on a Beowulf computing cluster and thus require parellization of algorithms, so it should expose a student to several interesting areas of both biology (DNA sequence analysis, protein sequence analysis, the sequence databases on the NCBI web site) and computer science (paralell processing, pattern recognition, string processing, statistical analysis, data mining).

 

    

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Eric Brown

Boise State University

Chemistry

ericbrown3@boisestate.edu

Research:

Human carbonic anhydrase II (HCA II) is a mononuclear zinc metalloprotein that catalyzes the reversible hydration of carbon dioxide to form bicarbonate. The enzyme has numerous physiological roles such as transporting CO2 from metabolizing tissues to the lungs, regulation of pH and balancing fluids within the human body. Much of the interest in the enzyme stems from the latter role where inhibitors are being developed for use in the treatment of glaucoma. Furthermore, recent interest in understanding how HCA II is able to activate CO2 has increased in the past decade because of the increasing need to develop a chemical method for eliminating greenhouse gases from the atmosphere. Our research is focused on understanding the mechanism of action of HCA II and to systematically examine the impact of hydrogen bonding on the stability and binding mode of the bicarbonate intermediate formed during the enzymatic cycle. To gain insight into these issues, we intend on using low molecular weight complexes that model the immediate coordination environment of the zinc ion and the H-bonding residues in the active site of HCA II. Novel ligand systems will be synthesized that provide an internal hydrogen bond but still allow variation of the steric properties so that tetrahedral mononuclear zinc hydroxide complexes can be isolated. In addition, we intend on understanding why differences in activity exist for the different substituted forms of HCA II by preparing divalent metal hydroxide complexes (Co, Cd, Ni, Mn and Cu) supported by our ligand systems and exploring their reactivity with carbon dioxide. We will access whether the coordination properties of the metal or hydrogen bonding interactions have a greater influence over the binding mode of the bicarbonate intermediate. Information obtained from these studies may then be used to develop a bio-inspired chemical method of reducing CO2 emissions.

Summer Project:

A fellow will begin by synthesizing novel ligand systems that model the three histidine residues and hydrogen bonding interactions found in the active site of the native enzyme. Once the ligands are isolated and fully characterized, metal hydroxide complexes will be synthesized and their reactivity with carbon dioxide explored. NMR, IR and X-ray crystallography will be used to examine the impact of hydrogen bond donors on the stability and binding mode (unidentate vs. bidentate) of the bicarbonate intermediate that is expected to form. Overall, a fellow will obtain multidisciplinary training in the synthesis and characterization of organic and inorganic compounds and, while the fellow will not perform biological studies, they will be exposed to the biochemical literature and the interdisciplinary aspects of bioinorganic chemistry.

 

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Dr. Henry Charlier

Boise State University

Chemistry Department

hcharlier@chem.boisestate.edu

 

 

Research:

 

     Anthracyclines are very important anticancer drugs that are associated with a potentially life-threatening cardiotoxicity.  This harmful side effect severely limits their use in cancer treatment.  Many studies have demonstrated that the cardiotoxicity is linked to the formation of an anthracline metabolite, the formation of which is catalyzed by carbonyl reductase.  The research conducted in my laboratory focuses on improving anthracycline chemotherapy through diminishing the risk of the associated cardiotoxicity. 

 

     Specifically, the research is aimed at preventing carbonyl reductase from generating the cardiotoxic metabolite.  Primarily, two approaches are ongoing:  1.  Developing and testing potential carbonyl reductase inhibitors and 2.  Designing and analyzing novel anthracyclines that are poor substrates for carbonyl reductase.  Both approaches could lead to anthracycline treatments that reduce the risk of anthracyline-induced cardiotoxicity, through preventing formation of the metabolite.

 

Summer Project:

 

1.  Synthesizing novel anthracyclines for both anticancer activity and as substrates for carbonyl reductase.

2.  Crystallizing human carbonyl reductase for eventual structure determination.

3.  Substrate specificity and enzyme mechanism studies.

4.  Inhibitor design and inhibition studies with human carbonyl reductase.

5. Other projects are also possible after discussion with student.

    

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Dr. Kenneth Cornell

Boise State University

Chemistry Department

kencornell@boisestate.edu

 

 

Research:

 

     My research focuses on the study of methionine (MET) synthesis and salvage.  We have identified several points in these metabolic pathways that differ between humans and pathogenic microbes that may be good targets for the development of antibiotics.  Since these portions of the metabolism of sulfur do not occur in humans, drugs that we develop should have low toxicities to patients.  As well, the microbial pathways are important since they are connected to the production of bacterial signalling molecules that govern such phenotypes as drug resistance. Our approach to studying these metabolic branchpoints is to: 1) clone and express the genes from a variety of pathogens (anthrax bacillus, E. coli, Giardia, etc.) and examine the properties of the recombinant protein; 2) characterize the native expression of salvage pathway genes in response to a variety of environmental and nutritional stimuli; and 3) test inhibitors of the microbial enzymes for their in vitro chemotherepeutic potential and ability to attenuate drug resistance.

 

     A related project involves the study of human methylthioadenosine (MTA) phosphorylase (MTAP).  MTAP degrades MTA into MET and purine salvage components.  Although the buildup of MTA  leads to inhibition of growth, a large number of leukemias and other tumor types are genetically deficient in MTAP, and thus cannor degrade MTA normally.  An unresolved question is what cellular adaptations occur in tumor cells to compensate for, or prevent, the build up of this growth inhibitory nucleoside?  We will examine cells in which the MTAP gene has been specifically deleted and compare the proteomic profiles to matched normal cells.  The results of these studies may highlight additional targets for anti-cancer agents as well as increase our understanding of the metabolic adaptations involved in MTAP deficient  tumor cells.                                            

 

Summer Project:

 

      A wide array of summer genetics/ molecular biology/ microbiology/ and enzymology projects are available depending on the student's interests.  These projects include:

 

  1. Cloning, expression and purification of Giardia lamblia MTA nucleosidase and MTR kinase salvage enzymes.

  2. Biochemical characterization of native and recombinant Giardia lamblia MTA nucleosidase and MTR kinase enzymes (substrate specificity, Km, Kcat).

  3. Creation of MTA nucleosidase and MTR kinase knock-out mutants of Giardia lamblia, E. coli, or Klebsiella pneumoniae.

  4. Analysis of MTA nucleosidase and MTR kinase gene expression during growth cycle / culture condition changes.

  5. Analysis of enzyme inhibitors for antimicrobial activity including ability to interfere with quorum sensing dependent biofilm formation and pigment production.

  6. Quantitation of quorum sensing signal molecule production as a function of MTA nucleosidase activity.

  7. Proteomic analysis of cytoplasmic and membrane proteins in normal and MTA deficient tumor cells.

  8. Biochemical and metabolic analysis of purine and methionine salvage enzyme activity in normal and MTA deficient tumor cells.

     Depending on the project, students will gain experience in a variety of cellular, molecular and biochemical techniques, including PCR, gene cloning, protein chromatography, HPLC, tissue culture, and enzyme kinetic analysis.

 

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Dr. Kevin Feris

Boise State University

Biology

kevinferis@boisestate.edu

http://www.boisestate.edu/biology/

Research:

 

The development of nanoscale materials and their incorporation into electronics, pharmaceuticals, and other manufactured products has outpaced our understanding of the interactions between these materials and biological systems.  A basic understanding of the toxicity of these materials, how they interact with biological systems, their thresholds of toxicity, modes of action, and impact on the environment is lacking.   

NanoBio research in my lab addresses questions such as:

        Are nanoscale metaloxides toxic?

        Can they be developed into novel antimicrobial agents?

        Can they affect the functioning of natural ecosystems?

 We are addressing these questions with a combination of approaches.  For, example our toxicity studies employ traditional microbiological techniques and controlled laboratory experiments with pure cultures of microorganisms as well as modern molecular microbial ecology techniques to understand community level responses to nanoparticles in an environmental context.  Nanobiotechnology is a rapidly progressing field and much remains to be learned about the fundamental nature of interactions between man made nano-sized particles and living systems.

 

 

Summer Project:

 

New mechanisms for providing protection from a variety of microbial pathogens and microorganisms inhabiting industrial processing systems are needed.  Development of novel antimicrobial materials is one way to satisfy this need.  Nanoparticles (NP) with sizes in the 1 – 100 nm range are very attractive materials for manipulation, sensing and detection of biological structures and systems; when reduced to the nanoscale regime, many benign materials develop toxicity.  Our group is investigating the toxicity mechanisms of transition metal oxide NP to microorganisms and primary human immune cells.  The student filling this position will study the antimicrobial properties of nano-scale metal oxides and explore development of NP thin films that could be used to create antimicrobial coatings for a variety of surfaces.  Specifically, the student researcher will be responsible for testing the antimicrobial properties of a suite of metal oxide NP against organisms such as Escherichia coli, Staphylococcus aureus, and Pseudomonas aeriginosa (among others).  Students with interest in medical microbiology and industrial microbiology are encouraged to apply for this project option.

 

 

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Dr.  Amit Jain

Boise State University

Computer Science Department

amit@cs.boisestate.edu

http://cs.boisestate.edu/~amit

 

 

Research:

 

Director of the Beowulf Cluster Lab. The Lab houses a 122 processor Beowulf cluster being used for High Performance Computing. The website for the cluster lab is http://cs.boisestate.edu/~amit/research/beowulf/


Current projects include converting programs from the areas of Geophysics, Bioinformatics, Mathematics, Engineering so that they can run fast on the cluster.


The Lab is sponsored by a national Science Foundation Major Research Infrastructure award no. 0321233.

 

Summer Project:

 

    Work on porting and installing parallel bioinformatics software on the Beowulf Cluster so that the biological community on the campus can make use of the cluster.


    Work with other students that are already working on bioinformatics software on the cluster.

 

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Dr.  Cheryl Jorcyk

Boise State University

Biology Department

cjorcyk@boisestate.edu

http://www.boisestate.edu/biology/jorcyk.htm

 

Research:

 

     Oncostatin M (OSM) is an Interleukin-6 family cytokine produced by breast cancer cells and tumor-associated cells of the immune system.  OSM has been shown to inhibit the proliferation of breast cancer cells, and this effect initially focused much attention on OSM as a potential breast cancer therapy.  Interesting data from our lab and from other labs suggests that OSM could actually contribute to breast tumor progression and metastasis.  In vitro, OSM promotes the development of a metastatic state by inducing the expression of proteases from breast cancer cells and promoting an increase in cell detachment.  We hypothesize that OSM enhances metastasis characteristics in prostate cancer cells, also.

     Our results could have significant implications regarding the development of experimental therapeutics.  If we can demonstrate that OSM promotes tumor progression by enhancing metastasis, then this would render OSM unsuitable as a cancer therapy.  In addition, results to this end would provide the foundation for the rational design of therapeutic agents that target OSM expression, function or signaling.  To date, there have been no attempts at inhibiting OSM for the purposes of cancer therapy.

 

Summer Project:

 

     In order to test our hypothesis, we plan to: 1) characterize OSM-induced protease expression in prostate cancer cells; 2) demonstrate that OSM promotes cell detachment; 3) demonstrate that OSM promotes cell invasion by showing that OSM enhances the invasion of prostate cancer cells through a synthetic extracellular matrix; 4) create a prostate cancer cell line that over-expresses OSM.  In future studies, this cell line and a control cell line will be injected into the tail veins and mammary fat pads of nude mice.  From these in vivo studies, we will be able to directly quantitate the effect of OSM on tumor progression and metastasis; and 5) study the effects of conditioned media collected from OSM-treated prostate cancer cells on endothelial proliferation and in vitro angiogenesis.

 

     Undergraduate and graduate students are currently involved in studies designed to determine the role of OSM in breast tumor progression and metastasis.  I am looking for a BRIN undergraduate student to initiate studies addressing the role of OSM in prostate cancer.

 

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Dr.  Byung I. Kim

Boise State University

Physics Department

ByungKim@boisestate.edu

http://www.boisestate.edu/physics/kim

 

 

Research:

 

    

Scanning-probe microscopy (SPM) provides excellent opportunities for the fundamental understanding of molecular-scale configurations of bio-molecules and their interactions in the biological environment.  Dr. Kim’s research is focused on the molecular-scale investigation of bio-molecular systems such as proteins, DNAs, cells, and bacteria in physiological fluid using novel SPM.  Currently, Kim’s group is studying the bio-molecular systems by imaging molecular structures on surfaces and/or probing bio-molecular interactions between bio-molecules.  As a unique approach, Dr. Kim’s group is developing a high-speed atomic-force microscope (AFM) for the molecular dynamics of motor proteins, and an interfacial force microscope (IFM) for probing the role of inter-/intra- molecular interactions in biological functions.  Dr. Kim is also interested in single-molecular manipulation of proteins using switchable bioactive surfaces, rapid detection, and analysis of biomolecular materials combining state-of-the-art communication skills and nanomechanical systems.

 

Summer Project:

Background: The antibody-antigen system is extremely important in understanding the immune-defence system. A new methodology for the understanding of the interaction between the antibody and antigen is to use atomic-force microscopy (AFM) to obtain direct information on the single-molecular antibody-antigen recognition.

Hypothesis: The hypothesis is that AFM is capable of measuring the biochemical kinetic parameters at the “single molecular level.”

Methods: The antigen is recombinant E. coli MTA/AdoHcy nucleosidase (MTAN), an enzyme responsible for cleavage of the hydrolytic cleavage of the glycosidic bond of two nucleosides involved in methionine and purine recycling.  The enzyme exists as a homodimer, with a subunit molecular weight of ~ 24kD.  The antibody is a mouse monoclonal antibody (IgG, 158kD) raised to the nucleosidase.  The AFM methodology can provide binding charactersitics at the “single-molecular level.”  The mentor and his undergraduate fellow students will investigate the interaction between the IgG2A antibody and MTAN in the biological environment to understand the antibody-antigen recognition at a single-molecular level using  the AFM system. The data will provide ample unprecedented information on the structure-function relationship in protein-protein interaction. The team will collaborate with Dr. Cornell at BSU.

 

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Dr. Bill Knowlton

Boise State University

MSE and in Electrical and Computer Engineering

bknowlton@boisestate.edu

http://coen.boisestate.edu/departments/faculty.asp?ID=20

 

Research:

OVERVIEW: Our group is performing bioengineering research towards a nanowire sensor for biomedical applications (e.g., immunoresponse sensor). The research team is highly interdisciplinary and composed of students whose majors are Materials Science and Engineering, Biology, Mechanical and Biomedical Engineering, Chemistry and Electrical and Computer Engineering.

PROJECT SPECIFICS: Nanowire electronic sensors have the promise of providing direct, real time, label-free detection and sensing of chemical and biomolecular agents. These attributes are highly attractive for many applications in medicine and the life sciences. As most nanowire sensors are inorganic (e.g., Si) or metallic, surface treatment with biomolecules is required in order to interact with biological sensor targets. Surface treatment of this type is unnecessary for biomolecular nanowires as they inherently provide multiple functional groups for bioengineering specific detection schemes for a sensor target. Additionally, bimolecular nanowires are more amenable for in vivo use as they are biomolecular in nature and thus offer increased biocompatibility.The biomolecular nanowire we are investigating are collagen monomers which are 300 nm long and 5 nm wide. Collagen monomers are attractive for several reasons. First, they have the ability to self-assembly into a range of thicknesses and lengths. Further, polypeptide chains of the collagen monomer provide multiple carboxylic acid, amine, alcohol, aldehyde, methyl, imidazole, and benzyl side chains, which can be utilized for the localized functionalization of the nanowire with target receptors. Assembly of the collagen monomer into collagen fibril nanowires provides a novel technology approach for nanowire sensor development that offers bottom-up fabrication and selective functionalization of the nanowire sensor.

Summer Project:

The Fellow assigned to our research group would work with the research team in a variety of ways to further our research goals. This includes developing atomic force microscopy (AFM) imaging, nanomechanical and/or electrical techniques, biochemical synthesis and characterization and/or performing and developing electrical measurement techniques.

 

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Dr. Owen McDougal

Boise State University

Chemistry

owenmcdougal@boisestate.edu http://chemistry.boisestate.edu/people/owenmcdougal/index.html

Research: 

Current research in the McDougal laboratory is focused on neurotoxins isolated from snails of the genus Conus. The objective of this research is to design, synthesize, and evaluate the efficacy of potent and selective antagonists of presynaptic neuronal nicotinic acetylcholine receptors (nAChRs).  Native alpha-conotoxin MII is a potent but non selective antagonist of alph6beta2 and alpha3beta2 subunits of neuronal but not muscle type nAChRs.  The E11A analogue of alpha-conotoxin MII is both potent and shows a 50-fold preference for binding to the alpha6beta2 nAChR subunit pair compared to the alpha3beta2 subunit combination. The design of selective antagonists will be based on a comparison of the structure of the potent but non selective alpha-conotoxin MII versus that of the potent and somewhat selective E11A analogue of alpha-conotoxin MII. The purpose is to understand the reason why the E11A analogue shows greater selectivity than the native alpha-conotoxin MII and design, synthesize, and test novel peptides that exhibit enhanced efficacy and selectivity. The significance of this work is that the alpha6beta2 subunits in presynaptic neuronal nAChRs have been found to control the release of dopamine in striatial cells of mice. The potential to develop therapies for diseases caused by improper dopamine levels in the brain including schizophrenia, Tourette’s syndrome, Parkinson’s, and Alzheimer’s is thus a possible outcome.

Summer Project: 

There are three components of the research project that students could be involved in.  First, the design of novel peptides is based on the nuclear magnetic resonance (NMR) derived structures of known peptides.  An NMR structure for the E11A peptide needs to be determined.  This will require a student to gain significant experience in data acquisition, analysis, and constraint set generation.  Structures will be generated based on NMR constraints using molecular mechanics software.  A comparison of structure characteristics between the E11A analogue and native alpha conotoxin MII will be required to rationally design novel peptides.  Secondly, the proposed peptides need to be synthesized.  This is done by solid phase synthetic strategies in a laboratory that has the instrumentation required.  A student working on this aspect of the project will take synthetic peptide attached to a solid support resin, perform sequential deprotection of cysteine amino acids and oxidize the peptide to form the correct arrangement of cystine bridges.  At each step along the way, reverse phase liquid chromatograhy (RPLC) separation is required.  Students here gain extensive experience in peptide folding and purificaiton.  The third aspect of this project is to express and purify the acetylcholine binding protein (AChBP) that serves as a receptor model for these studies.  The interaction between the AChBP and the synthetic ligand will be studied by spectrofluorimetry and nuclear magnetic resonance spectroscopy.

 

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Dr. Julia Oxford

Boise State University

Biology Department

joxford@boisestate.edu

 

 

Research:

 

   The research in my laboratory deals with the molecular mechanism of extracellular matrix assembly and how cells interact with their environment.  We focus on collagen molecules, investigating their structure and determining with what other molecules they interact.  Some diseases that may result from incorrect assembly of the extracellular matrix include osteoarthritis, retinal detachment, hearing loss, and problems with heart valve development. 

 

     Techniques commonly used in our laboratory include recombinant protein production and purification, protein unfolding and refolding, immunofluorescence, image analysis, PCR, 2-d gel electrophoresis, mass spectrometry, analytical ultracentrifugation, surface plasmon resonance as a measure of molecular interaction, and spectropolarimetry.

 

     One of the molecules that we focus on is collagen type XI.  Collagen type XI plays a regulatory role in the formation of collagen fibrils.  In the absence of collagen type XI, collagen fibrils become very large and lack normal interactions with another molecule of the extracellular matrix, called proteoglycan.  Without enough collagen type XI or in the case of a mutation in the gene encoding the protein as in Stickler syndrome, the cartilage is very soft and cannot withstand the forces to which the tissue is normally subjected.  The cartilage breaks down and arthritis develops early in individuals with Stickler syndrome.

 

Summer Project:

 

     Summer projects that we have planned include

 

     1) image analysis of immunofluorescence data from studies of extracellular matrix synthesis.  This work will utilize NIH Image software.  Established cell lines will be used to generate newly synthesized extracellular matrix.  The organization and molecular composition will be characterized using antibodies specific for isoforms of collagen XI to determine if there is an isoform-specific distribution of the different isoform.  Antibodies that recognize neoepitopes will also be used to follow the enzymatic processing of the collagen chains as they undergo maturation over time.

 

     2) characterization of posttranslational modifications by 2-d gel electrophoresis and mass spectrometric analysis.  Proteins synthesized by established cell lines will be used to identify the position of glycosylation, and the identity of the carbohydrate group on the amino terminal domain of collagen XI alpha 1 chain.  Posttranslational modifications may play a role in the molecular interactions of collagen type XI with other constituents of the extracellular matrix, thereby contributing to the structural integrity of tissues like cartilage.

 

 

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Dr. Jeffrey Peloquin

Boise State University

Chemistry

jeffreypeloquin@boisestate.edu

 

 

 

 

Research:

We are currently synthesizing manganese containing complexes that are mimics of the manganese catalase and manganese superoxide dismutase enzymes found in biological systems. These two enzymes are important components in the regulation of superoxide, peroxide and hydroxyl concentrations in cells since high concentration of these compounds can cause damage to cell membranes and DNA. Further, there is evidence that certain chemotherapy treatments can lead to an imbalance of these concentrations and result in cardiotoxicity.  We have two specific goals.  First, the target complexes will help us better understand the mechanism of natural enzymatic system.  Second, the synthesized complexes will form the basis for the rational design of manganese containing drugs for the treatment of oxidative stress brought about by chemotherapy. 

 

Summer Project:

A summer research student will be given the choice between three different projects.  The first subproject would involve the development and optimization of a synthetic protocol to introduce hydrogen bonding groups into our target ligand system.  As our basic synthetic framework is already determined, this project would require the student to determine at what point in the synthesis the functional group should be inserted as well as determine what protecting group would be required to allow the introduction of the new group.

 The second project would involve a student using laser spectroscopy, nuclear paramagnetic resonance spectroscopy or electron paramagnetic resonance spectroscopy to characterize the mechanism of manganese complexes synthesized to date.  This project would require some synthesis in order to create a supply of molecules but there would be little protocol development.

 The third project would be to use computational chemical programs to theoretically model the mechanism of the manganese complexes.  This project will not require any synthetic work but does require a student to have had physical chemistry or a strong math background. 

 

 

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Dr. Dale D. Russell

Boise State University

Chemistry

drussell@boisestate.edu

 

 

 

 

 

Research:

 

    There are presently 7 undergraduate students in my research group. Our focus is on inventing the tools to do analytical tasks better than the current methodologies. We use whatever techniques and materials best solve the problem. For example, we have developed electrochemical sensors to detect water-borne contaminants in the environment. These microsensors are very small, rugged, lightweight and field portable. They are designed to be carried to the environmental site of interest, dropped into bodies of water or down bore holes, or even dropped from aircraft into hostile environments. We have designed sensors for uranium, plutonium, arsenic, heavy metals, various organics and other contaminants of interest. We also work on the problem of separation and characterization of particulate materials that are not water soluble. The project available for the INBRE program is the separation and characterization of membrane proteins using filed flow fractionation in lipid medium, in order to retain native conformation and activity of the proteins. These projects result in invention of new analytical methods, and many of these projects have led to patents.

 

Summer Project:

 

    We are working to solve the difficult biochemical problem of separating and characterizing membrane-bound proteins while retaining their native conformation and enzyme activity. This research project is the separation and characterization of membrane proteins using electrical field flow fractionation. This method is similar to liquid chromatography, or gel electrophoresis, but with some important differences. Our goal is to retain native protein conformation and activity using this new method, for proteins that presently are denatured when analyzed by existing methods. The student on this project will learn instrument design, construction and optimization; protein extraction methods; currently-used protein analysis methods such as PAGE; and enzyme kinetic methods for determining protein activity. The student will contribute to development of a cutting-edge technique to solve a difficult biochemical problem.

 

 

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Dr. Michelle Sabick

Boise State University

Mechanical Engineering

MSabick@boisestate.edu

Research:

Dr. Sabick co-directs the Boise State University Intermountain Orthopaedics Sports Medicine & Biomechanics Research Laboratory (IOSMBRL).  The IOSMBRL is a collaborative effort between the departments of Mechanical & Biomedical Engineering and Kinesiology at Boise State, along with local clinicians with an interest in biomechanics research.  The IOSMBRL is a well-equipped motion capture laboratory housed in the BSU College of Engineering.  The lab uses a six-camera motion capture system with real-time capabilities, two floor mounted force plates, and a telemetric EMG system as well as commercial and custom software packages for image processing, musculoskeletal modeling, and data analysis.  Research focuses are in the areas of orthopaedics, sports medicine, and musculoskeletal modeling.  Examples of studies being conducted in the IOSMBRL include evaluating the effectiveness of an exercise intervention on the incidence of ACL injuries in high school athletes, injury mechanisms in little league baseball pitchers, the interaction between shoes and artificial turf on injuries in football players, and diagnosis of labral injuries in the shoulder.

Summer Project:

 

  • The effect of shoe cleat pattern on traction on artificial turf surfaces
  • Motions of the shoulder during clinical tests for labral tears
  • Musculoskeletal modeling of the female knee joint for assessment of ACL injury risk
  • Morphologic differences between healthy and damaged anterior cruciate ligaments

 

 

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Dr. Marion Scheepers

Boise State University

Mathematics

marion@math.boisestate.edu

 

Research:

My research interest are new computing paradigms, cryptology, game theory and mathematical logic (Set theory.  Molecular processes in biology have very strong analogies with theoretical models of computing. Certain protists, the ciliates, have two types of nuclei, one type somatic and the other type germline, in the same cell. The germline nucleus is an encrypted version of the somatic nucleus. Following conjugation, the new germline nucleus resulting from the conjugation is decrypted to form the new somatic nucleus, while the pre-conjugation nuclei are destroyed. This decryption process as well as the enzymes involved in it are of considerable interest because of the multiple potential applications of these processes and bio-technology.

Summer Project:

The project for this summer will involve isolating and identifying ciliates collected from the wild in Idaho, developing culturing protocols for these, characterizing their nuclear DNA and investigating transformation methods that can be successfully applied to these.

 

 

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Dr.  Juliette K. Tinker

Boise State University

Biology Department

juliettetinker@boisestate.edu

http://www.boisestate.edu/biology/tinker

 

 

Research:

 

     My research has focused on the development and characterization of bacterial enterotoxins as molecular tools and potential vaccines. The protein toxin secreted by the bacterium Vibrio cholerae, cholera toxin (CT), has long been known as a potent immunomodulator. When administered orally with other antigens of interest, this toxin can elicit a strong antibody response directed to the antigen of interest, indicating it has potential to act as an important oral vaccine adjuvant. Vaccine adjuvants are much needed "helpers" to stimulate immune responses to poorly immunogenic antigens. To date, there is only one vaccine adjuvant approved for use in humans, and there are no approved adjuvants that are effective when delivered orally. Bacterial enterotoxins, including CT and the E.coli heat-labile toxins (LTI and LTII), are extremely potent adjuvants when delivered orally in animal models, however, they are toxic, and not applicable for humans. My laboratory has developed chimeras that eliminate the toxic portion of the CT molecule while retaining the receptor-binding and adjuvant activity of the molecule. We are working to express and purify these proteins within the periplasm of E.coli so that the chimeras can be introduced into animal models and the immune response characterized. In addition, I am interested in better understanding the trafficking and signaling of these molecules within the eukaryotic cell, as well as characterizing novel bacterial toxins that may act as modulators of the immune system.

 

Summer Project:

 

     One potential project would be to construct plasmid vectors that will express Yersinia pestis antigens as a chimera with cholera toxin (CT) and E.coli heat-labile toxin (LT). These plasmids will be introduced into E.coli to allow production and purification of Yersinia pestis-CT or LT chimeric proteins. Ultimately, these proteins will be tested in mice as novel vaccines against infection with the plague bacterium.

 

     A second project in my lab would be analyzing the trafficking patterns of enterotoxin chimeras in tissue culture using fluorescence microscopy. We have constructed a number of fluorescent CT and LT chimeras which are of great value to examine the endocytosis pathway utilized by these toxins in eukayotic cells. Ultimately, this project will aid in better understanding of how these important bacterial toxins cause disease.    

 

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Dr. Don Warner

Boise State University

Chemistry Department

dwarner@boisestate.edu

 

 

Research:

 

    

An aziridinomitosene, a compound related to the clinically used anticancer agent mitomycin C, has recently been shown to form DNA interstrand cross-links under non-reductive conditions. The occurrence of the cross-link is significant for two reasons. First, mitomycin C prohibits cell proliferation via the formation of rare interstrand DNA cross-links. Second, aziridinomitosenes were previously thought to be responsible solely for formation of less toxic DNA monoadducts. Several factors may facilitate this previously unobserved cytotoxic event, including the presence of additional electrophilic sites on the quinone ring at C-6 and C-7. Evidence suggests that the C-1 and C-10 electrophilic sites are key to cross-link formation, as is the case with mitomycin C, but the molecular structure of the cross-link is not known. Of particular interest is a newly synthesized 6-methyl substituted aziridinomitosene which we now report to be more potent in arresting cell division in human promyelocytic leukemia (HL-60) cells than both mitomycin C and doxorubicin (see figure).  This compound and other target aziridinomitosenes will be characterized with regards to reduction potential, aziridine nitrogen pKa, solvolytic stability, and DNA alkylating ability.  This will help clarify the importance of various electrophilic sites on the molecule and lead to a better understanding of DNA-mitosene interactions.

 

Summer Project:

 

  

A student working in my lab would undertake one of several potential projects, depending upon specific career goals and interests. For example, a student could gain advanced organic chemistry skills through the synthesis of aziridinomitosene analogs, gain biochemistry skills by examining the propensity of the analogs to form DNA or DNA-protein cross-links, or gain computational chemistry skills by modeling DNA-aziridinomitosene adducts on the computer. Thus, projects are designed to accommodate the scientific interests of individual students.

 Since August 2002, approximately 38 students have worked in my undergraduate lab. These students have been incredibly hard-working and productive. As a result of their dedication, 22 students have been co-authors on poster presentations at local, regional, and national meetings. Further, we are currently preparing three manuscripts that will have eight different undergraduate student authors.

 

 

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