Suresh K. Joseph, PhD

Structure, function, and regulation of the inositol trisphosphate receptor (IP3R); biosynthesis and assembly of IP3R homo- and heteroligomers; mechanisms of proteosomal and lysosomal degradation of IP3R.

An elevation of the free calcium concentration in the cytoplasmic compartment is an integral component of the mechanism by which cells respond to many hormones, growth-factors and neurotransmitters. D- myo-Inositol 1,4,5-trisphosphate (IP3) is an intracellular messenger mediating the hormonal mobilization of Ca2+ from intracellular stores. This molecule interacts with a specific IP3 receptor ( IP3R ) that has been purified and shown to be a ligand-gated calcium channel. The work in my lab is focused on studying the structure, function and regulation of IP3 receptors.

The current projects in our lab include:

• Examining the gating mechanism by which IP3 binding leads to opening of the channel
• Identifying key residues in the ion conduction pore by mutagenesis
• Studying the molecular mechanism of the large structural changes in the receptor induced by calcium binding
• Investigating the role of the IP3R in apoptosis, particularly with reference to the finding that the channel is phosphorylated by Akt kinase.
• Studying the biosynthesis and degradation of IP3Rs. A major interest is the mechanism of agonist-mediated degradation which involves the ubiquitin/proteasome pathway.

The long-term goal is to understand how these proteins function in individual cells to generate complex spatial and temporal patterns in their Ca2+ transients and how such signals are decoded to alter physiological responses.

PhD, University of Bristol (1978)