Wednesday 16 July 2008: (Leiden) Extra Fysisch Colloquium, Harald Janovjak (14:00 hrs)



Harald Janovjak, Department of Molcular & Cell Biology, Univ. of California, Berkeley

Controlling Protein Structure and Function: With a Light Saber – and Force Powers

LION: Time: 14:00 hrs, Location: De Sitterzaal – Oortgebouw

The structure-function relationship of proteins steers physiological processes in all living organisms. My work focuses on novel biophysical techniques to (i) understand protein structure and folding in vitro and (ii) elucidate functional roles of specific proteins in native cellular contexts. We established atomic force microscopy to mechanically probe the stability of membrane proteins on a single-molecule level. In particular, we determined the parameters defining the energy landscapes of membrane proteins, such as co-existing (un) folding pathways and energy roughness, and followed single proteins non-invasively through the folding process. The ongoing challenge is to understand protein structure and function in native cellular environments. Cellular forces, e.g. those generated by motor proteins, have periodic signatures. We devised a novel molecular dynamics simulation approach to gain first insight into the nano-mechanical response of proteins subjected to periodic forces. Even for small proteins we observed a very complex behavior that included shifts in unfolding pathways and transient refolding. We consider our results a first step towards a theoretical framework for protein stability in vivo. To elucidate functional roles of specific proteins in cellular networks, we developed nano-technological tools to control protein function using light. Light can be applied to living cells non-invasively, spatially focused and under rapid temporal control. Several concepts to control cellular processes using light will be introduced. Using small optical switch molecules we were able to manipulate the structure and function of glutamate receptors as a first step towards remote controlling cellular processes.