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Research overview

In essence I am interested in cell signalling with a particular emphasis on those involved in the control of exocytosis. The molecular mechanisms (stimulus-secretion coupling) which control regulated secretion still remain only partially characterised and this is especially true for secretion of hormones from endocrine glands. My interests in stimulus-secretion coupling mechanisms started when I undertook my Ph.D research project in the Department of Pharmacology at the University of Glasgow looking at the involvement of cAMP in the control of prolactin secretion from rat GH3 anterior pituitary tumour cells. This interest in cell signalling continued into my postdoctoral research project at the NIH where I focused upon the interaction between cAMP and calcium ions upon secretion from what has now become my model secretory system of choice the mouse AtT-20 anterior pituitary cell line. I discovered that increases in cAMP stimulated hormone secretion from these cells by a dual action of both enhancing calcium entry into the cells and potentiating the effects of calcium upon the secretory apparatus. This post-calcium, late stage point of interaction has been the focus of my researches ever since. This led me to consider a role for G-proteins in the late stages of the endocrine secretory pathway, the G-exocytosis (Ge) postulated by Gomperts at the time of my postdoctoral studies. At this point I started using electrically permeabilised cells to permit the control of intracellular calcium concentrations and I observed the ability of GTP analogues to stimulate secretion from AtT-20 cells in the absence of any changes intracellular calcium ions. This confirmed a role for Ge in AtT-20 cells and that this was the point of interaction between cAMP and calcium I had observed earlier. The search for the identity of Ge has led me to believe it to be one of the following G-proteins; Gz, G12, G13 or ARF6.My interest in finding the point of interaction between G-proteins and calcium signalling pathways has led me to consider the role of neuronal calcium sensor 1 (NCS-1) in stimulus-secretion coupling in AtT-20 cells. Using a NCS-1 overexpressing cell line we have shown a role for NCS-1 in the secretory pathway in AtT-20 cells. The connection between NCS-1 and Ge is being sought.

Research publications

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