Dr. John A. Tainer
The University of Texas MD Anderson Cancer Center
Department of Molecular and Cellular Oncology
My laboratory's research centers on connecting structures of nano to micro-scale macromolecular machines to seeing, predicting, and controlling biological outcomes for cancer, health, and biotechnology. Research includes developing advanced methods to integrate X-ray crystallography and X-ray scattering (SAXS) at our MD Anderson synchrotron beamline facilities (see sibyls.als.lbl.gov) with results from EM and NMR and with single molecule measurements to achieve accurate, comprehensive visualizations with functional flexibility. We focus on the characterization of keystone complexes, conformational changes, and interfaces controlling stress responses. We emphasize characterizations of connections joining aspects of reactive oxygen control, genome integrity, cell proliferation, pathogenesis, and cell death, as well as DNA transcription, replication, recombination, and repair. We are particularly interested in developing predictive mechanistic knowledge pertaining to how macromolecular machines control assembly, conformation and chemistry for the regulation and control of stress response networks impacting biological outcomes at the organism level. Exemplary projects on macromolecular machines include complexes and interactions of MRE11-RAD50-NBS1, DNA-PK, RAD51-RAD51C, FEN1-PCNA, DNA2, TFIIH, superoxide dismutase, and DNA repair helicase and nuclease complexes relevant to human health, bio-manufacturing and synthetic biology. Our structural biology results furthermore furnish inspiration for the design of protein assemblies such as cages for medicine and synthetic biology. General goals for these projects are to enable a quantitative, predictive knowledge of stress responses for biology and medicine. Specific goals are to uncover health implications from human genome polymorphisms and to develop allosteric inhibitors as enabling tools to control reactive oxygen and DNA damage response pathways for medicine and biology.
We have sequences from the world most extreme thermophilic organism - these will would allow a rotation student to express and purify otherwise challenging targets that promise to unveil fundamental mechanisms for stress responses to DNA damage and replication stalling relevant to cancer.