High Pressure Research on Protein Structure

Lately I have been applying up to 2 kilobar (200 MPa) to proteins using a simple Beryllium high pressure cell, and collecting crystallographic data on crystals of a mutant of lysozyme. The mutant is interesting because it has a large cavity created by mutating Leu99 to Alanine. (Image courtesy of Michael Quillin, University of Oregon) Measuring the cavity requires some sophistication. I currently use software based on the Alpha shapes research of Herbert Edelsbrunner. Incidentally, I have ported some of his code to the Mac OSX operating system. If you are interested in this, please contact me and I'll tell you how to fix their code for Mac. I believe that under their license agreement, I am not allowed to redistribute the fixed code. In any case, we have found some curious things about the mutant protein's behavior under pressure, none of which I currently at liberty to broadcast here. Let it suffice to say that we are examining our results carefully.

Older Work

Research on Membrane Proteins

I study a number of things having to do with membrane proteins--proteins that do their work in the membranes of cells. Proteins in cell membranes help provide structure to the membrane, act as pores for salts, help communicate with the rest of the body through hormone receptors, and recieve light signals, the first step in vision. Bacteria use a protein similar to the proteins involved in vision, but for different purposes: navigation and to gather energy from sunlight.

A majority of protein structures are determined by use of X-ray diffraction, and this requires crystals of the proteins. This leads to a difficulty: most crystals are grown out of solutions in water. But membrane proteins don't like being in water--they want to be in a membrane. Recent techniques have managed to crystallize bacteriorhodopsin (bR) out of a membrane like structure, a liquid crystal of lipids called a "bicontinuous cubic phase". I am attempting to understand the physics that underlies this technique.

Below, you'll find three presentations which should give you a rough introduction to what I do. They are aimed at a somewhat technical audience. Feel free to e-mail me if you have questions about this work. You'll also find technical references in each presentation.

Bacteriorhodopsin function

Membrane Protein Crystallization

Membrane Protein Crystallization (a more recent presentation for a CHESS Journal Club meeting)

I am also working with scientists at the Cornell High Energy Synchrotron Source (CHESS) to develop methods to study the tiny crystals made using these techniques. This will involve a great deal of work, and it is just beginning. More on this as it develops.