Gating of Bacterial Transporters and Ion Channels involved in Ion Homeostasis. (360G-Wellcome-086903_Z_08_Z)

Ion channels and transporters play major roles in cellular homeostasis, as exemplified by our work on mechanogated (MscS & MscK) and electrophile activated (KefC) channels. We have made considerable progress in understanding the gating of these two channel types including defining the open structure for MscS (submitted for publication) and the structure of the regulatory domain of KefC (in preparation). Our future programme will concentrate on developing these novel insights, but specifically to integrate into our research synthetic chemistry approaches that will provide the basis for interventions via deregulating the activity of these systems. I have identified collaborators at San Diego State University (SDSU) with whom we have undertaken preliminary studies of peptides that appear to interact with mechanosensisitve channels. In addition, our work on KefC gating has reached a crucial stage were more frequent interaction with the crystallographer (Roosild), who is based in Nevada , would be extremely valuable for the development of the structural analysis of gating, but also for defining objectives for synthetic chemistry approaches. Finally, there is a strong metagenomics group at SDSU and with them we will develop methods for analysing channel gene expression in bacterial communities.