BIOGENESIS AND STRUCTURE-FUNCTIONANALYSIS OF THE MSCS MECHANOSENSITIVE CHANNEL IN E COLINEW INVESTIGATORS AWARD

Biogenesis and Structure-Function analysis of the MscS Mechanosensitive channel in Escherichia coli

Bacterial cells have developed many ways to adapt to changes in their environment. These adaptive mechanisms aid cell survival and so an understanding of these systems will provide novel therapeutic targets. One example is the mechanosensitive channels, MscL and MscS. Ion channels are involved in many life processes. They are gated conduits permitting ions and solutes to travel across cell membranes. The mechanosensitive channels are proteins embedded in the membrane that act as pressure valves. When bacteria are transferred from concentrated to more dilute environments they experience a rapid inflow of water, which increases pressure directed from the cell interior onto the surrounding cell membrane. This raises the lateral pressure, i.e. the stretch within the bacterial cell membrane, which above a certain threshold causes MscS and MscL to gate. The open channels allow passage of internal cell contents, which relieves the internal pressure and allows cell survival. Cells lacking the channels lyse when transferred from concentrated to dilute environments. I am interested in the structure of MscS, the gating mechanism, and how the channel assembles in the bacterial cell membrane. I will use molecular and biochemical techniques to define regions of the protein essential for these processes and therefore essential for proper channel function. I will gain a better understanding of the molecular mechanisms that occur during MscS channel gating and how this channel is formed in cells. The proposed research will investigate fundamental aspects of MscS gating and assembly, which will be relevant to other MS channels.