Yale E. Goldman, MD, PhD

Description of Research Expertise

Research Interests
Relating the structural changes to enzymatic reactions and mechanical steps of the energy transduction mechanism by mapping the real-time domain motions of the motor proteins and ribosomal elongation factors.

Key words: Actin, Molecular motor, Motility, Myosin, Structural dynamics, Fluorescence, Muscle, Ribosome, Protein synthesis, G-Protein, ATPase, Laser Photolysis, Caged ATP, Optical Trap.

Description of Research
Motor proteins and GTP-binding proteins (G-proteins) share many structural and functional attributes. Muscle is a prototype biological energy transducer that can be understood at a particularly fine level of detail. The nearly crystalline organization of actin and myosin within a fiber allows the reaction sequence to be probed by biophysical, physiological, chemical and structural studies. A cyclic interaction between actin and myosin transforms free energy of splitting ATP into motion and mechanical work. Modified forms of this mechanism power other cell biological motions such as targeted vesicle transport and cell division. We are using novel biophysical techniques, including laser photolysis of ‘caged molecules’, bifunctional fluorescent probes and single molecule fluorescence polarization to map the real-time domain motions of the motor proteins.

Although the ribosome has been studied extensively since the unraveling of the genetic code, how it accomplishes the enormous fidelity of messenger RNA translation into amino acid sequences during protein biosynthesis is not understood. The ribosome is a motor translocating along the mRNA exactly 3 bases per elongation cycle. Energy from splitting GTP by G-protein elongation factors (EFs) is transformed into translational accuracy and maintenance of the reading frame. Codon-anticodon base pairing between mRNA and tRNA ‘reads’ the code, but EF-Tu ‘proofreads’ it. EF-G may be the motor. Powerful techniques developed for studies on motor proteins, including single molecule fluorescence and optical traps, may be applied to understand the structural biology, energetics and function of EFs in their working environment.

Rotation Projects for 2003-2004
- Unconventional Myosins
- Dynein/Myosin Interactions
- Protein Synthesis
- Ribosomal Elongation Factors

Lab personnel:
Dr. Jody Dantzig-Brody, Research Faculty
Rama Kudaravalli, Research Technician
JoAnn Rodgers, Administrative Coordinator
Huy Pham, Research Technician
Graham Dempsey, Research Technician
Jennifer Petrina, Business Administrator
Jennifer Ross, Research Faculty
Yuhong Wang, Research Faculty
Yujie Sun, Research Faculty
Joby Geevarghese, Electrical Engineer

Description of Other Expertise

Academic Experience:
1969 Graduated with highest distinction, Northwestern University;
1975 Upjohn Achievement Award, University of Pennsylvania;
1971-1975 Trainee, Medical Scientist Training Program, University of Pennsylvania;
1975-1977 Research Fellowship, Muscular Dystrophy Association;
1977-1979 National Research Service Award, (NIH);
1980-1985 Research Career Development Award, (NIH);
1982-1985 Ad hoc member of the Physiology Study Section (NIH);
1983-1988 Editorial Board Member, Journal of Physiology (London);
1984-1986 Editor for Special Topic Section of Annual Reviews of Physiology;
1985-1987 Elected Councillor of the Society of General Physiology;
1986 Bowditch Lecturer of the American Physiological Society;
1987 Chairman, Gordon Conference on Muscle: Contractile Proteins;
1989 Lindback Foundation Award for Distinguished Teaching;
1990 Lamport Lecturer of the University of Washington, School of Medicine;
1990-present Elected Councillor (Executive Committee) of Biophysical Society;
1991 Organizer, American Physiological Society Specialty Conference;
1991 Visiting Professor, Osaka University, Japan;
1992-present Editorial Board Member, Biophysical Journal;
1995 Distinguished Speaker for Graduate Student Research Forum, University of Cincinnati