Just as steel girders support modern skyscrapers, actin filaments give cells their shape and strength. But actin has many other roles: it drives cells to migrate and change shape; its regulation is crucial in preventing cancer, tumor metastasis, and immunodeficiency disorders; and the actin cytoskeleton is rearranged by bacteria and viruses when they infect cells.
Michael Rosen wants to learn how signals from outside the cell regulate the actin cytoskeleton. A chemist by training, he studies the physical basis of that information flow by examining the three-dimensional arrangements of atoms in individual actin molecules and how they interact with their binding partners. Colleagues say his broad technical expertise and ability to complement these structural studies with an array of biophysical and biochemical techniques have brought him to the forefront of the field.
To reorganize the actin cytoskeleton and set itself in motion, the cell needs to create new actin filaments. Actin molecules floating around inside the cell tend to shun each other. But individual molecules will congregate and form a filament once they spy a cluster of two or three actin molecules. Rosen's laboratory helped show how the two main triggering molecules work to start the linear filament growth.
Much of the work by Rosen and others is moving on from the mechanics of individual molecules to the complex behavior of molecules and cells in living systems, the core of systems biology. Rosen wants to model the additional properties of circuits that are not present in any given molecule in the network. The large and multifaceted proteins in the actin signaling networks provide a test case to model the dynamic cellular events and eventually to identify points of therapeutic intervention.
