Dr. Malcolm’s research interests focus on how bacteria sense their environment and how we can utilize that machinery as potential targets for antibiotics. Some of the novel targets are members of the MscS (mechanosensitive channel of small conductance) superfamily. The MscS superfamily is composed of fifteen unique subfamilies all containing significant homology to the E. coli MscS homologue, such as the bacterial cyclic nucleotide (bCNG) gated and the MscCG, the MscS variant in Corynebacterium glutamicum, subfamilies. E. coli MscS gates in response to tension in the membrane and plays a role in cell survival in response to hypo-osmotic shock. Preliminary evidence suggests that many of the members in the MscS superfamily undergo similar molecular transitions within their unique gating cycles. We will study how members of the MscS superfamily of ion channels gate in response to different stimuli applied to the bacterial membrane through patch clamp electrophysiology. In some bacterial genomes multiple bCNG channel genes have been identified and biochemical analysis of heterologous expression indicates that these two bCNG channels form heteromultimers. In addition to multiple bCNG homologues many bacterial genomes encode for several MscS superfamily members, we will utilize RNA analysis to determine if the mRNA levels of these superfamily members change in response to different growth conditions.
