First, we alter the chemistry of adhesion molecules systematically and measure the resulting affect on adhesion in carefully constructed assays. This algorithm represents a wonderful tool to test systematically the relationship between adhesion molecule properties and cell adhesion in ways that are not feasible experimentally. Our efforts in cell adhesion research have led to a number of fundamental insights. Also, we were the first lab to calculate the complete phase diagram of adhesion, relating adhesion molecule properties to the dynamics of adhesion. Future work in this area will focus on systematic alteration of adhesion molecule function, analysis of structure-function relationships of adhesion molecules, and the development of mutated forms of adhesion molecules with altered structure.
Viruses are fascinating, compact biological packages whose sole goal is to infect host cells.
A step in the viral infection cascade is membrane fusion, where the outer lipid bilayer of the virus fuses with a membrane of the host cells. The coalescence of these two membranes allows the genetic material of the virus to enter the host cell nucleus. This fusion is mediated by proteins on the viral surface, which are designed to cause membrane coalescence, often at low pH. We have been interested in the mechanism of fusion, and how it is controlled by the physical chemistry of the viral adhesion molecules and the lipid chemistry of the cell membranes. We have studied how small fragments of the fusion molecule on influenza virus destabilizes biomembranes. Our long term goal is to reconstitute the fusion activity of viral molecules into larger structures, such as vesicles and cells, to measure the mechanics and dynamics of fusion using micropipette aspiration, in which the fusing membranes are held in close proximity and known applied force by small diameter micropipettes.