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ALAN FRIEDMAN
| Associate Professor LILY B-129 494-5911 CV: Link |
Our research seeks to understand biological structure and its relationship to function by employing a combination of experimentation (structural biology/biophysics) and computation (computational biology/bioinformatics) to answer questions that neither can answer alone. The questions include elucidating structural information from challenging systems and interpreting the interactions that are revealed by structure elucidation to understand function.
In elucidating structural information we use the unique ability of computational methods to simulate outcomes and sift through enormous numbers of possibilities in order to plan the most informative experiments to conduct. We then employ traditional biophysical and biochemical techniques (e.g. crystallography, solution x-ray scattering, ultracentrifugation, cross-linking, site-directed mutagenesis) particularly in variant and hybrid methodologies that we are developing (e.g. planned disulfide-trapping, planned stability mutagenesis and decomposition of x-ray scattering from heterogeneous solutions) to probe the real behavior of these systems. The data is then analyzed also with the help of computational methods of our own devising.
In interpreting structure to explain function we have developed a series of methods for making and using chimeras of homologous proteins to probe the interactions between protein units. These methods also employ computation to design the most informative sets of chimeras. Chimeras are then created robotically using our recently-developed gene assembly planning and robotic control software and analyzed for stability and activity by well-established means. Here too, computational models and analyses help us interpret the experimental data.
The model biological systems that we employ for both kinds of studies are drawn from our longstanding interests in the damage that results to macromolecules upon aging and their repair by cellular processes and by the interaction of organisms as they form symbiotic, mutualistic or parasitic relationships. These are both questions where macromolecular structure intersects with important evolutionary strategies to determine the health and longevity of organisms and ecosystems.
Education
Ph.D., Yale, 1989
Professional Faculty Research
(Structural biology) Structural cell biology of infection, immunity, and aging.
Other Activities
- Argonne Labs, Argonne, Illinois, July 10, 2003. Site visit review for the BioCAT beamline as a collaborating investigator.
Faculty Presentations
- Combining bioinformatics and rapid experimentation in protein structure: multimodel discrimination of protein fold, Department of Biochemistry, Case Western Reserve University, Cleveland, Ohio, June 20, 2003.
- Protein expression and characterization to enable multimodel discrimination of protein and protein complex structures, DOE-sponsored discussion of a Protein Purification and Characterization Facility, Argonne National Labs, February 4, 2004.