Graduate Studies Faculty
Michael S. Chapman, Ph.D.
Programs:Biochemistry & Molecular Biology
Program in Molecular & Cellular Biosciences
Research Interests:Virus structural biology; Gene therapy vectors; Enzyme mechanism & dynamics; X-ray crystallography; Experimental biophysics, biochemsitry & molecular biology; Computational methods; » Click here for more about Dr. Chapman's research » PubMed Listing
Preceptor RotationsAcademic Term Available Fall 2016 Yes Winter 2016 Yes Spring 2016 Yes Fall 2017 Yes Winter 2017 Yes Spring 2017 Yes
Faculty MentorshipDr. Chapman is available as a mentor for 2016-2017.
Michael Chapman earned a B.Sc.(Hons) in Cellular & Molecular Biology from King's College (1982), and an M.Sc. in Crystallography from Birkbeck College (1983), also within the University of London. His Ph.D. in Biochemistry from the University of California, Los Angeles (1987) researched the atomic structure of the photosynthetic enzyme, RuBisCO, with David Eisenberg. Post-doctoral research at Purdue University, with Michael Rossmann, involved structural studies of parvoviruses and picornaviruses. He spent 13 years on the faculty of Florida State University, ending in 2006 as Professor of Chemistry & Biochemistry and Director of the Center for Biomolecular Computer Modeling & Simulation. He joined the faculty of OHSU in the Fall of 2006.
- Projects are in three areas that combine structural and functional studies to elucidate the workings and interactions of biological macromolecules:
• Viral-host interactions, underpinning the development of vectors for in vivo gene therapy vectors.
• Enzyme structural dynamics and mechanism.
• Computational methods for improving structures derived from biophysical data.
Structual Biology of Viral-Host Interactions
Adeno-associated Virus (AAV) is being developed as a vector for gene therapy - to transport DNA into cells to remedy the effects of genetic defects. The outer protein shells of viruses are responsible for receptor attachment in cell entry and are recognized by antibodies in immune neutralization. Studies focus on the virus structure and its interactions with host molecules by x-ray crystallography, electron microscopy and molecular biology. The motivation is both pure & applied, to advance the fundamental understanding of viral-host interactions, to learn how to re-target vectors to different cells, and how to evade immune neutralization of therapeutic vectors.
Enzyme Mechanism & Dynamics
The Protein Data Bank provides still images of 80,000 structures. Althouth it is well known that macromolecules are not static, but highly dynamic, technical challenges leave only a handful with motions characterized in the timescales that are crucial for function. Nothing is known about the protein dynamics at the heart of bringing substrates into a reactive configuration in the active site of a multi-substrate enzyme. We are addressing this gap with biophysical studies of arginine kinase, using a combination of x-ray crystallography and NMR spectroscopy to characterize the structural transitions and rates of motion at critical points in the reaction pathway. With arginine kinase, we have developed a model system that is accessible to the required techniques with which we are learning the fundamental general principles of how proteins operate.
Structure Refinement - Methods development
Biomolecular complexes and cellular machines can sometimes be divided into components for study by x-ray crystallography, but their intact size usually demands electron microscopy, a lower resolution technique. Hybrid methods build models of the complex from known component structures. The Chapman group is developing methods for refining complex structures so that they best fit the available electron microscopy data while remaining consistent with the physics of molecular interactions. The emerging methods are tested on our own investigation of virus-host interactions, and applied to studies of conformational change in other complexes such as the ribosome.
Further details of the research & publications of the Chapman group are available at http://xtal.ohsu.edu/