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Grant #P20RR016454
funded by
NIH
NCRR

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Boise State University and the Boise VA Medical Center Prospective
Mentors
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Name:
Institute:
Department:
Email:
Website:
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Dr. Tim Anderson
Boise State University
Computer Science
tim@cs.boisestate.ed
http://cs.boisestate.edu/~tim/
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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 |
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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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Email:
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Dr. Henry Charlier
Boise State University
Chemistry Department
hcharlier@chem.boisestate.edu
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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
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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:
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Cloning, expression
and purification of Giardia lamblia MTA nucleosidase and MTR kinase
salvage enzymes.
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Biochemical
characterization of native and recombinant Giardia lamblia MTA
nucleosidase and MTR kinase enzymes (substrate specificity, Km, Kcat).
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Creation of MTA
nucleosidase and MTR kinase knock-out mutants of Giardia lamblia, E.
coli, or Klebsiella pneumoniae.
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Analysis of MTA
nucleosidase and MTR kinase gene expression during growth cycle /
culture condition changes.
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Analysis of enzyme
inhibitors for antimicrobial activity including ability to interfere
with quorum sensing dependent biofilm formation and pigment production.
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Quantitation of quorum
sensing signal molecule production as a function of MTA nucleosidase
activity.
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Proteomic analysis of
cytoplasmic and membrane proteins in normal and MTA deficient tumor
cells.
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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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Email:
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Dr. Kevin Feris
Boise State University
Biology
kevinferis@boisestate.edu
http://www.boisestate.edu/biology/ |
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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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Name:
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Dr.
Amit Jain
Boise State University
Computer Science
Department
amit@cs.boisestate.edu
http://cs.boisestate.edu/~amit
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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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Name:
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Email:
Website:
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Dr.
Cheryl Jorcyk
Boise State University
Biology Department
cjorcyk@boisestate.edu
http://www.boisestate.edu/biology/jorcyk.htm
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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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Email:
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Dr.
Byung I. Kim
Boise State University
Physics Department
ByungKim@boisestate.edu
http://www.boisestate.edu/physics/kim
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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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Name:
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Email:
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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
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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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Email:
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Dr. Owen McDougal
Boise State University
Chemistry
owenmcdougal@boisestate.edu
http://chemistry.boisestate.edu/people/owenmcdougal/index.html
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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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Name:
Institute:
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Email:
Website:
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Dr. Julia Oxford
Boise State University
Biology Department
joxford@boisestate.edu
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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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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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Name:
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Department:
Email:
Website:
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Dr. Dale D. Russell
Boise State University
Chemistry
drussell@boisestate.edu
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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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Name:
Institute:
Department:
Email:
Website:
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Dr.
Michelle Sabick
Boise State University
Mechanical Engineering
MSabick@boisestate.edu
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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:
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The effect of shoe
cleat pattern on traction on artificial turf surfaces
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Motions of the
shoulder during clinical tests for labral tears
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Musculoskeletal
modeling of the female knee joint for assessment of ACL injury
risk
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Morphologic
differences between healthy and damaged anterior cruciate
ligaments
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Name:
Institute:
Department:
Email:
Website:
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Dr. Marion Scheepers
Boise State University
Mathematics
marion@math.boisestate.edu
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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
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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
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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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