Development of Photoactive Transition Metal 5-Membered Ring Quinone Methideanalogs
Potential Anti-cancer and Anti-tumor Drug Design
Neil Allison, PhD
Department of Chemistry & Biochemistry, University of Arkansas, Fayetteville

The quinone methide moiety has been reported to be possible bioreductive alkylators of DNA as well as alkylators of nucleic acid bases. A goal of the Allison research group is to study the preparation and chemistry of 5-membered ring quinone methide analogs that are bonded to a transition metal. In contrast to quinone methides, we can vary the metal and ligands to control reactivity.

Pre-requisite courses: Organic Chemistry I and II.

Bioinformatics students:  No

Bioseparation systems design
Robert R. Beitle, PhD & Ralph Henry, PhD
Ralph E. Martin Department of Chemical Engineering, and Department of Biological Sciences, University of Arkansas, Fayetteville

This joint project between biological science (Ralph Henry) and chemical engineering (Robert Beitle) introduces a new and powerful concept by which recombinant proteins of commercial, therapeutic, or academic interest may be isolated when affinity tail technology is used to dictate purification. Work will focus on the optimization of protein purification via the technique of Immobilized Metal Affinity Chromatography (IMAC). We have cataloged genomic proteins of Escherichia coli that bind chelated metal ions during IMAC. Based on our results it has been established that eight proteins constitute over 50% of the potential contaminating genomic proteins of E. coli. When these eight are eliminated or mutated via genetic means the purification process will be greatly improved. Anticipated benefits would include but not be limited to reductions in (i) the regiment of chromatography, (ii) column capacity loss due to contaminating protein adsorption, and (iii) complexity of elution protocols since the number of proteins to be resolved are less.  Such an effort to date has not been documented in literature.

 

Students are sought with background in (i) molecular biology, (ii) chemical or biological engineering, or (iii) math sciences. Specific tasks would likely be (i) collecting proteome data, (ii) scaling the lMAC process to larger systems, or (iii) modeling the system.

Pre-requisite courses: None

Bioinformatics students: Yes

Quantitative proteomic analysis of the protein complexes functioning in programmed cell death

Yuchun Du, Ph.D.
Department of Biological Sciences, University of Arkansas, Fayetteville

Mass spectrometry based quantitative proteomics involves using stable isotope to differentially label proteins or peptides, and mass spectrometry to compare the relative abundance of the proteins in different samples. Research in Du laboratory focuses on using multidisciplinary approaches including techniques from quantitative proteomics, biochemistry and cell biology to identify and characterize protein complexes that play critical roles in programmed cell death. 

Pre-requisite courses:  None

Bioinformatics students:  Yes

Control of Immune Responses
Cell Signaling in Immune Memory and Stability of Genes in the Immune System
Jeannine Durdik, PhD
Department of Biological Sciences, University of Arkansas, Fayetteville

The Durdik laboratory studies the control of immune responses, considering a competition between allergic and inflammatory responses. The ability to make a protective immune response by preferentially inducing inflammatory responses is being tested by chemically modifying recombinant antigens from bird pathogens. A second research area of cell signaling in immune memory is being examined using pentoxifylline, a phosphodiesterase inhibiting drug, which, when given during the development of a primary response, enhances the memory responses of T cells. The mechanism by which pentoxifylline decreases death in responding lymphocytes is being explored. In a third project, the stability of genes is considered in testing the hypothesis, that double-stranded break repair of DNA in older individuals is impaired and that this affects the development of lymphocytes in aged animals.

Pre-requisite courses: None

Bioinformatics students:  Yes

Development of Photoactivated Ruthenium Complexes to study Biological Electron Transfer
Bill Durham, PhD & Frank Millett, PhD
Department of Chemistry and Biochemistry, University of Arkansas, Fayetteville

This laboratory is involved in developing novel photoactivated ruthenium complexes to study biological electron transfer reactions. Currently mitochondrial electron transfer in several proteins involved in the electron transport chain, including cytochrome c, cytochrome oxidase, and cytochrome bc1 is being studied.

Pre-requisite courses: None

Bioinformatics students:  Yes

Miniature Biosensors and Bioassays

Ingrid Fritsch, PhD

Department of Chemistry and Biochemistry, University of Arkansas, Fayetteville

Research in the Fritsch lab involves bioanalytical chemistry. It includes interfacing various materials that are suitable for miniature biosensors and bioassays with selected biological compounds. Projects include immobilization of molecules onto surfaces, studies of stability of activity, microfluidics to achieve automation and manipulate nanoliter to picoliter volumes and electrochemical detection of pathogens and biomarkers important in medical diagnostics and environmental applications.  In certain cases, we write computer simulations that can be used in combination with experiments to better understand results and design new biosensor and bioassay devices.

Pre-requisite courses:  Freshman Chemistry & organic chemistry

Bioinformatics students:  Yes

Molecular Biology of Plant Immunity

Fiona L. Goggin, Ph.D. 

Department of Entomology, University of Arkansas, Fayetteville.

The Goggin laboratory uses molecular and genomic tools to study the mechanisms through which plants defend themselves against attack by insects and other herbivores.  The ultimate goal of this work is to identify means of enhancing herbivore resistance in crop plants in order to reduce yield losses and pesticide usage.  Our laboratory can offer training in standard techniques for gene expression analysis (eg. quantitative RT-PCR) as well as techniques to suppress expression of genes that have been selected for functional analysis (eg. virus-induced gene silencing). web site: http://entomology.uark.edu/faculty/goggin.html

Pre-requisite courses: None

Bioinformatics students:  Possibly

Protein Targeting
Ralph Henry, PhD & Suresh Kumar, PhD

Department of Biological Sciences, Department of Chemistry and Biochemistry, University of Arkansas, Fayetteville

A joint laboratory project focuses on proteins that function to target newly synthesized proteins to biological membranes. A combination of biochemical and biophysical tools, including PCR-based cloning and large-scale expression/purification of proteins, will be used to investigate protein-protein interactions between these components, specifically interactions that result in targeting to receptors and transporters at the membrane.

Pre-requisite courses: cell biology

Bioinformatics students:  No

Molecular Adaptations to Life at High pH;
Virulence Genes of the Intestinal Pathogen Clostridium difficile
Mack Ivey, PhD
Department of Biological Chemistry, University of Arkansas, Fayetteville

Research in the Ivey laboratory focuses on the biochemical and genetic mechanisms by which bacteria respond to their ionic environment. Microbiological, molecular genetic and biochemical techniques are used in the investigation of an unusual ATP synthase isolated from a bacterium that lives in extreme environments. A second project involves the molecular characterization of ion transporters and other potential virulence determinants in the intestinal pathogen Clostridium difficile.

Pre-requisite courses: None

Bioinformatics students:  Yes

In silico and In vitro Study of Reactive Oxygen Species and Nitric Oxide

Interactions in the Microcirculation

Mahendra Kavdia, Ph.D.

Department of Biomedical Engineering, University of Arkansas, Fayetteville

The Kavdia Laboratory uses experimental and computational methodologies to model biological systems and apply these methodologies to understand underlying mechanisms of disease.  The research focus is to provide quantitative understanding of nitric oxide (NO) and reactive oxygen species (ROS) interactions in physiology and pathophysiology at the molecular and cellular level. Understanding of these molecular interactions and biotransport  NO and ROS is clinically important and may provide therapeutic opportunities in areas as diverse as sickle cell anemia, pulmonary hypertension, septic shock, NO inhalation, and blood substitutes (HBOCs), cardiovascular disorders, diabetes related vascular complications, atherosclerosis , ischemic-reperfusion injuries.   

Pre-requisite courses: None

Bioinformatics students:  Yes

Biophysics of Membrane Channels
Roger Koeppe, PhD  

Department of Chemistry and Biochemistry, University of Arkansas, Fayetteville

To study the biophysics of membrane channels, the synthesis, labeling and purification of membrane-active peptides are used. Protein/lipid structural and dynamic interactions are analyzed using deuterium magnetic resonance spectroscopy, circular dichroism spectroscopy, and other methods.

Pre-requisite courses: None

Bioinformatics students:  No

Synthesis of Anti-Cancer Natural Products
Matt McIntosh, PhD
Department of Chemistry and Biochemistry, University of Arkansas, Fayetteville

The McIntosh group is involved in the synthesis of natural products with potential anti-cancer activity. The research program will develop novel synthetic methods and apply these methods to the synthesis of complex organic molecules.

Pre-requisite courses: 1 year of organic chemistry

Bioinformatics students:  No

The Role of Differential Gene Expression in Candida albicans Pathogenesis
David S. McNabb, PhD
Department of Biological Sciences, University of Arkansas, Fayetteville

The McNabb laboratory studies the mechanisms by which the regulated expression of various genes in Candida albicans affects the pathogenic properties of this opportunistic human pathogen. Approaches include molecular genetic techniques, the biochemistry of protein-nucleic acid interactions, the analysis of gene expression using whole-genome microarrays, and the use of animal models and tissue culture to study the pathogenic properties of various C albicans mutants that are generated in the laboratory.

Pre-requisite courses:  None

Bioinformatics students:  Yes

Bio-Medical Applications of Colloidal Nanocrystals
Xiaogang Peng, PhD

Department of Chemistry and Biochemistry, University of Arkansas, Fayetteville

Research in Dr. Peng’s laboratory will explore the use of colloidal nanocrystals for the detection and manipulation of biological targets. Colloidal nanocrystals are nanometer-sized crystals that can be dispersed in solution. In principle, those tiny crystals should be unique tools for biomedical research, for both diagnostic, as well as treatment protocols. Dr. Peng’s group is regarded as one of the leading groups in the world in the synthesis and manipulation of colloidal nanocrystals.

Pre-requisite courses: None

Bioinformatics students:  No

Mitotic Chromosome Segregation in Yeast
Inés Pinto, PhD

Department of Biological Sciences, University of Arkansas, Fayetteville

The main goal of Dr. Pinto’s research is to understand how chromatin structure affects chromosome segregation. The budding yeast Saccharomyces cerevisiae is used as a model system. This lower eukaryote offers the advantage of being amenable to many types of analyses, including cell biology, molecular genetics and biochemical techniques. A multi-disciplinary approach is used to investigate a basic biological process.

Pre-requisite courses: None

Bioinformatics students:  No

Genomics, Gene Expression and Mapping Genes affecting

Fertility and Pulmonary Hypertension Syndrome

Doug Rhoads, PhD

Department of Biological Sciences, University of Arkansas, Fayetteville

The Rhoads laboratory uses advanced methods of genome analysis to identify, and map genes involved in development of genetic diseases affecting chickens: Pulmonary Hypertension Syndrome, and Sperm Mobility. The chicken is being used as a medical model to understand these complex traits in humans. We have identified the critical regions and are fine mapping these regions through PCR genotyping and bioinformatic analysis of candidate genes. We are also investigating a large number of novel RNAs produced in the chicken reproductive tract. This project uses plasmid sequencing, bioinformatics, and qPCR to characterize the genes through sequence analysis and expression analysis. Website: http://biscweb.uark.edu/drhoads 
Pre-requisite courses: Cell Biology; Genetics

Bioinformatics students:  Yes

3-Dimensional Structural Analysis of Protein-ligand Complexes
Joshua Sakon, PhD

Department of Chemistry and Biochemistry, University of Arkansas, Fayetteville

Detailed structural studies of medically relevant proteins can reveal subtle features concerning the interaction of the protein and its binding partners. From this information, lead compounds may be developed using structure-based drug design methodology. Techniques include protein isolation, protein crystallization and structural characterization using x-ray crystallography.

Pre-requisite courses: None

Bioinformatics students:  No

Molecular phylogenetics of anaerobic protists (parasites and free-living relatives).

Jeffrey D Silberman, PhD

Department of Biological Sciences, University of Arkansas, Fayetteville

 The Silberman lab takes a multifaceted approach to discovering, describing and inferring the evolutionary history of anaerobic protists. Single cell eukaryotes (i.e., protists) comprise the vast majority and diversity of eukaryotes.  The ability to live and thrive in a multitude of low-oxygen environments (such as anaerobic sediments as well as within the guts of many animals) has evolved independently numerous times.  Molecular techniques (gene isolation and DNA sequencing) and comparative gene analyses are the primary tools used to infer phylogenies. Protist ‘discovery’ is accomplished through culturing experiments and culture-independent gene isolation (i.e., environmental PCR). New-to-science organisms are described via light microscopy and photo-documentation. Lineages of particular interest include Entamoeba, Trichomonads and numerous ‘odd ball’ anaerobic amoebae and flagellates. 

Pre-requisite courses: None

Bioinformatics students: yes

In Vivo Microdialysis Sampling Studies for Monitoring Signaling Molecules.

Julie Stenken, Ph.D.

Department of Chemistry & Biochemistry Chemical Biology, University of Arkansas

Our bioanalytical chemistry laboratory focuses on making direct measurements as well as improving the ability to make measurements within awake and freely moving mammalian systems.   Microdialysis sampling is a widely used and successful sample collection method to obtain analytically-clean samples from very complex matrices such as mammalian tissues, bioreactors, or environmental samples.  There are numerous potential projects that could be tailored for students and faculty within the Arkansas INBRE program.  Our current major focus has been aimed towards improving peptide and protein sampling using the microdialysis sampling approach.  Systems of interest include: 1. Detection of cytokines and matrix metalloproteinases in situ within wound sites.  2. Modulation of cytokines and MMPs during wound healing. 3. Measurement of neuropeptides related to addiction. 4. Measurement of peptides and proteins (e.g., insulin, leptin) related to obesity and metabolic syndrome.  Common analytical techniques frequently used in this laboratory include ELISA, HPLC, flow cytometry-based immunoassays, and mass spectrometry.  

Course Prerequisites:   Freshmen Chemistry. 

Bioinformatics Students:  Yes.  

Engineering Protein Stability and Structure
Wesley Stites, PhD
Department of Chemistry and Biochemistry, University of Arkansas, Fayetteville

The leading cause of premature death in smokers is cardiovascular disease. Diabetics also suffer from increased cardiovascular disease. This results, in part, from the hypercoagulable state associated with these conditions. However, the molecular cause(s) of the elevated risk of cardiovascular disease and the prothrombotic state of smokers and diabetics remain unknown. It is well known that oxidative stress is increased in both conditions. In smokers, it is established that oxidation of methionine residues takes place in α1-antitrypsin in lungs and that this leads to emphysema. Thrombomodulin is a key regulator of blood clotting and is found on the endothelium. Oxidation of methionine 388 in thrombomodulin is known to slow the rate at which the thrombomodulin-thrombin complex activates protein C, a protein which, in turn, degrades the factors which activate thrombin and lead to clot formation. In analogy to the cause of emphysema, we hypothesize that oxidation of this methionine is elevated in smokers relative to non-smokers and, perhaps, in conditions such as diabetes that impose oxidative stress on the body. Evidence for the hypothesis has been found and we continue work to prove or disprove it.  More generally, aside from smoking, aging and diseases such as diabetes are also well known to be accompanied by oxidative stress and many complications of these conditions appear related to this stress. Oxidative stress has been shown to be linked to oxidation of methionine side chains in proteins to the sulfoxide form. Methionine sulfoxide formation has also been shown to affect the biological activity of proteins other than thrombomodulin and may be a general regulatory mechanism. However, no systematic effort has been made to survey the human proteome for this oxidative modification nor to determine how it changes with age, disease state, or smoking status. This is, in part, due to the fact that it is fairly difficult to detect this modification. The development of methods to detect methionine sulfoxide formation in the proteome is another project ongoing in our laboratory.

Pre-requisite courses: none

Bioinformatics students:  Yes

Bioanalytical Mass Spectrometry

Charles L. Wilkins, PhD

Department of Chemistry & Biochemistry, University of Arkansas, Fayetteville

Our research involves development and use of advanced mass spectrometric methods for application in a variety of proteomics-related studies. Among those techniques are Fourier transform and matrix-assisted time-of-flight mass spectrometry for direct analysis of intact cells from bacteria and other organisms. In this way, it is possible to use characteristic protein and lipid mass spectral patterns for classification down to the strain level. Using the same whole cell methodology, we are also developing ways of monitoring recombinant bacteria and fungal protein expression systems to follow the process of producing specific over-expressed proteins. This allows detection of undesired variants that may be produced and permits estimates of the efficiency of the particular expression systems. Identification of proteins detected is also of use in searching for biomarkers that can serve as potential sensor elements for devices designed to rapidly and specifically detect pathogenic organisms or toxins.

Pre-requisite Courses: Freshman Chemistry and Organic Chemistry

Bioinformatics students: Yes

Information for Mentors

Mentors at University of Arkansas at Little Rock

Mentors at University of Arkansas for Medical Sciences