Nick Guydosh

A.B. 2001 Harvard University
M.Phil 2003 Cambridge University

I became part of the Block lab in the summer of 2003 with an interest in applying the first-rate optical trapping technology in the lab to some intricate questions in enzyme mechanism. In particular, I am interested in understanding how the chemical and mechanical cycles on each head of the kinesin motor are coupled to produce motion from the energy released during ATP hydrolysis. I am also interested in understanding how this mechanochemical cycle on each head remains synchronized with that on the partner head. Synchrony of the heads is essential for keeping one head attached to the microtubule track at all times and enabling kinesin to move processively over long distances.

I am approaching this problem by measuring the motion of single molecules of truncated, monomeric and full-length, dimeric kinesin constructs in the presence of nucleotide analogs that slow or inhibit steps in the biochemical cycle. Initial results have shown that the front head of kinesin is inhibited when the rear head is tightly bound to the microtubule and that it is the ATP binding step within the kinetic cycle that triggers kinesin to take an 8-nm mechanical step along the microtubule.

I was born and raised near Binghamton, NY. I first discovered my interest in molecular biophysics and Stanford University while working as a summer REU student, under Professor Steve Boxer here, on techniques for control of supported lipid bilayers. I developed my interest further, under Professor Sunney Xie at Harvard, where I learned the techniques of single molecule fluorescence detection and conformational dynamics of flavin enzymes. I then took a year on a Churchill Scholarship to learn more about protein structure, stability, and the kinetics of folding through research under Professor Sir Alan Fersht, at the MRC and Cambridge University. This was the time I also finally figured out how to find a good pint, pilot a punt, and learn greetings in myriad foreign languages. Following this, I came to Stanford in the fall of 2002 to start a Ph.D. in biophysics.