The focus of research in the laboratory relates to signal transduction mediated by cyclic nucleotides. We investigate molecular mechanisms of signaling by receptor guanylyl cyclases, phosphodiesterases and novel nucleotide cyclases in bacteria.
The receptor guanylyl cyclase C is a ligand-stimulated guanylyl cyclase that is involved in the maintenance of fluid-homeostasis and intestinal cell division and differentiation. Just as 'turning on' of a signaling pathway is regulated, the 'turning off' of a pathway is also closely monitored within cells, and therefore we study cyclic nucleotide phosphodiesterases, such as the cGMP-binding cGMP-specific phosphodiesterase 5, which is allosterically activated by cGMP, and hydrolyzes cGMP to GMP, thus shutting down cGMP-mediated signaling. We have also identified an evolutionarily conserved novel phosphodiesterase which may have a role to play in neuronal cell biology.
The wealth of genome information coupled with large scale computational analyses have revealed the presence of a large number of Class III nucleotide cyclases, phosphodiesterases and cyclic nucleotide binding proteins in bacteria and archaebacteria. We are involved in carrying out systematic studies on the Class III adenylyl cyclases encoded in the genome of Mycobacterium tuberculosis H37Rv, as well as identifying and characterizing novel cyclic nucleotide phosphodiesterases and cyclic nucleotide binding proteins in mycobacteria.
Our research activities in these areas are described on pages below.