Being about to join a medical school, I have a growing interest in G protein coupled receptors (GPCRs). The reason is that 30% of the 800 known GPCRs are drug targets, and some of them are the targets of multiple drugs (half of the drugs target a GPCR, according to an interesting article in the current issue of The Scientist). GPCRs appear to control many processes, eg appetite, smell, heartbeat, sleep, etc. Some are involved in development (e.g. GPR50-null mutant mice never begin puberty), while at least another one can mediate retroviral entry (eg CCR5, targeted by anti-HIV Maraviroc). GPCRs usually bind a ligand, but some of them simply block other GPCRs by dimerizing with them (eg GPR50 blocks MT1 this way).
Could computational/systems biology help understand how GPCRs work ? Maybe. I am curious to see what the GPCR co-expression network (eg across human tissues) is like and how that correlates with drug targeting, whether that can predict heterodimerization or drug side effects. Since there is a lot of data about transcriptional response to drug treatment (eg, with the Connectivity Map from the Broad), it seems to me that it would also be interesting to ask how the transcriptional program upon treatment with drugs targeting different GPCRs actually differ (and whether there is some overlap). Also I am curious to see where GPCRs are expressed in the brain. If anybody has any other ideas, or is interested in working on some of these problems, please shoot me an email.
