Department of Chemistry and Biochemistry

Faculty: Timothy C. Mueser, Ph.D.

Office: WO 4211
Phone: (419) 530-1510
Fax: (419) 530-4033

Professional Background:
B.S. Chemistry, Eureka College, 1983;
Ph.D. Chemistry, University of Nebraska-Lincoln, 1989;
Iowa Cardiovascular Center Institutional Research Fellow, University of Iowa, 1992;
NIH Postdoctoral Fellow, University of Iowa, 1993;
NIH IRTA Fellow, NIAMS National Institute of Health, 1993-1998;
NIH Senior Staff Fellow, NIAMS National Institute of Health, 1998-2000.


Research Interests:
Biophysical chemistry and macromolecular crystallography.
Visualizing protein:protein and protein:DNA complexes using X-ray crystallography.
Analysis of PLP dependent enzymes and nucleases using neutron crystallography.

Prof. Mueser’s Ph.D dissertation research at The University of Nebraska – Lincoln under the guidance of Prof. Lawrence J. Parkhurst involved the development of a piezo-modulated laser excitation fluorescence polarization stopped-flow for rapid reaction studies of protein:ligand interactions. Postdoctoral research involved single-crystal X-ray diffraction studies of vertebrate hemoglobins conducted at the University of Iowa – Iowa City in the laboratory of Prof. Arthur Arnone. Staff Scientist position at the National Institutes of Health was in the laboratory of Dr. Craig Hyde who solved the crystal structures of porcine aspartate aminotransferase (AAT) in a collaboration with Prof. Arnone and Prof. David Metzler at Iowa State University, Ames Iowa. Craig also solved the structure of tryptophan synthase (TS) in a collaboration with Dr. David Davies, and Dr. Edith Miles at the National Institutes of Health, Bethesda Md. AAT and TS are the focus of our current neutron diffraction studies of PLP dependent enzymes. While at NIH, structural studies of the bacteriophage T4 DNA replication system were begun in collaboration with Dr. Nancy G. Nossal, Chief, Laboratory of Molecular and Cellular Biology, NIDDK National Institutes of Health. The structures of T4 RNase H, a 5' to 3' exonuclease of the RAD2 family of enzymes, and the gene 59 helicase assembly protein, a structure specific DNA binding protein were completed.

The University of Toledo:
Research here continued the research on bacteriophage T4, a virus that infects bacteria, which is well established as a model system for understanding the complex interactions required for DNA replication, repair, and recombination. We have reported studies on the analysis of gp59 with the gp41 helicase, the T4 RNH in complex with branched DNA, and the gp59:gp32 complex (supported by an NSF CAREER award). A review “Structural analysis of bacteriophage T4 DNA replication: a review in the Virology Journal series on bacteriophage T4 and its relatives” provides an overview of this work.

Neutron Diffraction: 
During a sabbatical at Oak Ridge National Labs with Dr. Paul Langan and Dr. Leighton Coates, neutron scattering and diffraction methods were added to the research program. Neutron diffraction allows the visualization of protons (deuterons) which are absent in X-ray diffraction structures. The neutron diffraction structure of liganded R-state hemoglobin allowed comparison of the protonation state of residues involved in the Bohr effect. We have recently completed the neutron structure of AAT (Nature Comm in press) in collaboration with Dr. Andrey Kovalevsky and Dr. Jerry Parks, ORNL, and Dr. Matthew Blakeley, ILL Grenoble. Steven Dajnowicz has been awarded a Battelle ORNL GO! fellowship and is completing his Ph.D. dissertation research at ORNL.

Microgravity Research:
The low flux of neutron sources necessitates the need for very large (>1 mm^3) crystals. A collaboration with Prof. Constance Schall, University of Toledo Dept. of Chem. Eng., investigates the effect of protein solubility on crystallization. These studies led to crystallization trials on the International Space Station delivered by SpaceX 4. Our current research, funded by CASIS/NASA, is to use microgravity to improve crystallization growth for neutron diffraction. Our next flight will include hydrogenated and perdeuterated PLP dependent enzymes, AAT and TS, and the T4 RNH and T4RNH:gp32 complexes.

Last Updated: 6/27/22