I began studying the regulation of intracellular Ca2+ signaling initially by identifying genes for intracellular Ca2+ channels in the model genetic organism Drosophila melanogaster while on sabbatical at Brandeis University, Waltham, USA (Hasan and Rosbash, 1992). Amongst these my group went on to study the Inositol 1,4,5-trisphosphate receptor (InsP3R) by generating several classes of mutants in the itpr gene. These mutants were characterized at genetic, molecular and functional levels (Joshi et al., 2004; Sinha and Hasan, 1999; Srikanth et al., 2006; Srikanth et al., 2004; Venkatesh and Hasan, 1997).
Briefly, our recent work has demonstrated that reducing InsP3R function in Drosophila neurons affects feeding and growth in larvae (Agrawal, 2009) and multiple aspects of flight circuit development and function in pupae and adults (Banerjee et al., 2004). These studies have shown that putting InsP3R function back in neurons which either synthesise monoamines (like serotonin) or insulin-like peptides (ILPs) rescues itpr mutant defects in larvae and adults (Agrawal, 2009; Joshi et al., 2004). More recently, projects to understand how itpr mutants respond to changes in regulation of intracellular store Ca2+ (Banerjee et al., 2006; Venkiteswaran and Hasan, 2009) and to stress conditions (S. Manivannan, unpublished) have been initiated. Work from my group has demonstrated for the first time in a physiological context the requirement for store-operated calcium entry downstream of InsP3 signaling in neurons (Agrawal et al., 2010; Hasan and Venkiteswaran, 2010). The results from these studies suggest that genetic and pharmacological methods could be used for controlling intracellular Ca2+ homeostasis in the context of certain neurodegenerative and metabolic diseases.
I have maintained an interest in my early post-doctoral work on Drosophila olfaction in collaboration with the lab of Prof. Veronica Rodrigues. Possible similarities between visual and olfactory transduction had been suggested in the 1990s by early work from the Carlson group. We undertook the study of olfactory transduction in Drosophila. Electrophysiological responses from the Drosophila antennae are normal in itpr mutant alleles (Deshpande et al., 2000; with a small but significant effect on adaptation), but are compromised in null alleles for genes encoding Gq (dgq) and PLCb ?(plcb21C) (Kain et al., 2008). This was the first demonstration of the requirement for PLCb21C in Drosophila olfactory transduction.