Research — Biochemistry and Molecular Biophysics

(M15 900)
Cross-listed with L41 (Bio) 590

Wayne M. Barnes, PhD
2nd Floor McDonnell Science Building
We are developing a new way to sequence DNA, under the “$1000 Genome Project”.  This project involves the addition of experimental fluorescent probes to DNA polymerase, with the goal of watching a single molecule flicker as it copies DNA.  Student involvement may be at the level of making mutations and purifying mutant enzymes, testing ways to prepare the templates, or testing observations of working molecules.

T7 RNA polymerase is used to expresss our proteins, and we have double and triple mutants of it that improve expression of problematic proteins, but we only have theory as to how they work better:  we think they are slower, and that slower is better.  Student involvement may be in constructing comparative strains that use the enzyme, and measuring the speed somehow, in vivo and in vitro.

Peter M. J. Burgers, PhD
1st Floor South Building
Molecular biology of DNA replication, DNA damage response mechanisms, and DNA repair in eukaryotes.

Carl Frieden, PhD
2nd Floor McDonnell Science Building
Investigation of apolipoproteins E as they relate to Alzheimer’s Disease. Mechanisms of protein aggregation. Fibril formation and bacterial infections.

Eric A. Galburt, PhD
2nd Floor McDonnell Science Building
Use of single-molecule biophysical techniques such as magnetic and optical trapping to study DNA transcription.

Roberto Galletto, PhD
2nd Floor McDonnell Science Building
Mechanistic studies of DNA motor proteins and telomere binding proteins; single-molecule approaches.

Kathleen Hall, PhD
2nd Floor North Building
RNA structure/function. RNA protein interactions. NMR spectroscopy.

Timothy M. Lohman, PhD
2nd Floor North Building
Biophysical chemistry of proteins, nucleic acids and their mechanism of interaction. Mechanisms of DNA unwinding and translocation by helicases and SSB proteins.

Garland R. Marshall, PhD
2nd Floor Cancer Research Building, Center for Chemical Genomics
Targeting Epigenetic Control in Pathology. A major concern regarding the use of therapeutics targeting the epigenetic control of gene expression is undesirable side effects, particularly those associated with fetal development. Despite the intense interest in targeting histone deacetylases (HDACs, eleven zinc-based enzymes expressed in humans) for multiple therapeutic applications and the fact that two non-specific HDACIs are already FDA-approved in oncology, isoform-specific HDACIs are not available. Professor Marshall and his collaborators in Rome have a comprehensive program to develop isoform-specific inhibitors for applications for reversing HIV latency with Professor Lee Ratner for treatment of HIV, with Dr. Michael D. Onkin for treatment of uveal melanoma, and for potential antiparasitics with Professors Dan Goldberg, Eva Istvan, Makedonka Mitreva and Audrey Odom. Two uniquely specific inhibitors of HDAC6 have already been discovered in the Marshall lab in the past month.

The research involves bioinformatics to identify homologs of HDACs in parasites, molecular modeling to generate homology models of target proteins, virtual screening to identify potential inhibitors and bioassays to quantitate efficacy. Projects can be customized to fit individual preferences.

Linda Pike, PhD
1st Floor South Building
Mechanism of EGF and ErbB receptor function.  We use a combination of radioligand binding and molecular imaging via luciferase fragment complementation to study the interactions of ErbB family receptors.  The goal is to gain insight into structure/function relationships within these receptors to better understand how to target them therapeutically.

Gregory Bowman, PhD
253C McDonnell Medical Sciences Building
Systems Biophysics. We combine simulation and experiment to understand the conformational changes proteins undergo and how these changes allow information to flow, both within single proteins and within networks of interacting proteins. Two major application areas are (1) understanding hidden allosteric sites and the opportunities they present for drug design and (2) understanding the molecular mechanisms of vision, especially the origins of inherited forms of blindness. To facilitate these applications, we also develop enhanced sampling algorithms for simulating long timescale dynamics of proteins and nucleic acids