Howard Hughes Medical Institute Investigator
Luis Alvarez Professor of Physics
Professor of Molecular & Cell Biology
Professor of Chemistry
University of California, Berkeley

Tuesday, May 27th, 2008
Clark Center Auditorium
Stanford University

Poster presentations from
ME382 Medical Device Design and Evaluation Project Class,
Biomechanical Engineering and the Stanford Biodesign Innovation Program

Posters available for viewing in the Clark Center Courtyard at 2:30 p.m.

Lecture by Carlos Bustamante, Ph.D.
4:35 p.m. to 5:45 p.m.

Reception
5:45 - 7:00 p.m.
Clark Center Courtyard
Stanford University

For further information, please see:
http://www.stanford.edu/group/biomech/distinguished.html
Or contact Melanie Cole at mcole@stanford.edu or 650-723-8024
For parking near the Clark Center at Roth Way, please see the google map link

Abstract of Lecture

As part of their infection cycle, many viruses must package their newly replicated genomes inside a protein capsid to insure proper transport and delivery to other host cells. Bacteriophage_phi29 packages its 6.6 mm long double-stranded DNA into a 42 nm dia. x 54 nm high capsid via a portal complex that possesses 5 ATPases that hydrolyze ATP. This process is remarkable because entropic, electrostatic, and bending energies of the DNA must be overcome to package the DNA to near-crystalline density. We have used optical tweezers to pull on single DNA molecules as they are packaged, thus demonstrating that the portal complex is a force generating motor. We find that this motor can work against loads of up to ~57 picoNewtons on average, making it one of the strongest molecular motors ever reported. Movements of over 5 mm are observed, indicating high processivity. We establish the force-velocity relationship of the motor and find that the rate-limiting step of the motor's cycle is force dependent even at low loads. Interestingly, the packaging rate decreases as the prohead is filled, indicating that an internal pressure builds up due to DNA compression. We estimate that at the end of packaging the capsid pressure is ~6 MegaPascals, corresponding to an internal force of ~52 pN acting on the motor. We have also investigated the coordination between the mechanical and the chemical steps in the motor operation and have proposed the first putative cycle for this molecular machine. We determine, within this cycle, the step at which the chemical energy is converted into mechanical work and we characterize the nature of the interactions between the motor and the DNA. Finally, high resolution optical tweezers experiments are enabling us to investigate in detail the operation of this motor and the coordination among ATPases during the overall cycle.

Previous Distinguished Lecturers

2007 Van C. Mow, Ph.D.
Columbia University


2006 Jay D. Humphrey, Ph.D.
Texas A&M University


2005 Farshid Guilak, Ph.D.
Duke University


2004 Roger D. Kamm, Ph.D.
Massachusetts Institute of Technology


2003 Stephen C. Cowin, Ph.D.
The City College, New York, New York


2002 Robert M. Nerem, Ph.D.
Georgia Institute of Technology


2001 Shu Chien, M.D., Ph.D.
University of California, San Diego


2000 Peter S. Walker, Ph.D.
Cooper Union Research Foundation, New York


1999 Savio L-Y. Woo, Ph.D.
University of Pittsburgh


1998 Peter Davies, Ph.D.
University of Pennsylvania


1997 R. McNeill Alexander, Ph.D., FRS
University of Leeds


1996 Donald E. Ingber, MD, Ph.D.
Harvard Medical School


1995 Albert B. Schultz, Ph.D.
University of Michigan


1994 Timothy M. Wright, Ph.D.
Cornell University Medical College


1993 Yuan-Cheng Fung, Ph.D.
University of California, San Diego


1992 Thomas A. McMahon, Ph.D.
Harvard University