Professor Guy A. Rutter

My interests in cell signalling and metabolic control began in 1985 and a PhD with RM (Dick) Denton FRS in Bristol on the regulation by Ca2+ of mitochondrial dehydrogenases. In 1991, I joined Claes Wollheim in Geneva on an MRC Travelling Fellowship where I extended these studies to the control of insulin secretion. I was lucky enough in this two year period to make two discoveries of fairly fundamental importance with respect to -cell metabolism and glucose sensing. Firstly, using recently-developed recombinant mitochondrially-targeted Ca2+ probes, I showed that glucose and other depolarising stimuli cause mitochondrial Ca2+ uptake (1), and that the -cell's metabolic configuration is geared to ensure that the vast majority of glucose carbon is converted to CO2 and water, and hence ATP synthesis, thanks to the absence of lactate dehydrogenase or lactate transport activities (2).

In 1993 I returned to Bristol's burgeoning Biochemistry department. There, I set up single cell approaches to study the secretory responses of -cells to glucose in the newly-instituted MRC Imaging Facility in Bristol (3;4). I was awarded a HEFC Lectureship in 1995, and established a lab focussed on insulin secretion. I was subsequently made a Full Professor of Biochemistry and Cell Biology in 2002 and a Research Leave Fellow of the University and then the Wellcome Trust (2003-2006). With nine others, I was involved in a successful bid for ~£10 m JIF support to establish Bristol's Henry Wellcome Laboratories for Integrated Cell signalling in 2001.

My lab was amongst the first to use of recombinant bioluminescent and fluorescent probes and novel imaging approaches to monitor and manipulate signalling systems in the living ß-cell (5;6). I used these, and mouse genetics, to delineate the role of the fuel-sensitive kinases AMP-activating protein kinase (7-11) and per-arnt-sim (PAS) kinase (12) in glucose sensing, and the cell cycle regulator, ZAC (13) in transient neonatal diabetes. My work on beta-cell physiology was recognised with the Minkowski prize of the European Association for the Study of Diabetes (EASD) in 2004 (14).

Seeking to determine the extent to which the recognition of fuels and hormonal stimuli in the brain may resemble that in the islet, I began a collaboration in 2001 with Mike Ashford wherein we extended to hypothalamic neurons our technologies for imaging ATP, calcium and pyridine nucleotides. Our finding that ATP fluctuated liitle in neurons, but more so in surrounding glia (15), subsequently led to our finding a role for AMPK in the control of glucose-inhibited, AgRP/NPY neurons (16).

My laboratory has enjoyed continuous support from the Wellcome Trust since 1997, as well as grants from MRC, BBSRC, NIH, HFSP, JDRF, EU and DiabetesUK. I served on the Biochemical Society Council (2000-2003), and have sat regularly on NIH (2003, 2007), JDRFI (2001-), DUK and, since 2004, the Wellcome Trust's Physiological Sciences Panel (co-vice chair for 2007-2008). I served as an Editor of the Biochemical Journal from 1999-2004 and as an Editor of Diabetes since 2006. I was recruited to Imperial College in late 2006 to head a new Section of Cell Biology focussed on molecular mechanisms of diabetes and obesity.

Rutter, G. A. et al (1993) J. Biol. Chem. 268, 22385-22390
Sekine, N. et al (1994) J. Biol. Chem. 269, 4895-4902
Rutter, G. A. et al (1995) Curr. Biol. 5, 890-899
Rutter, G. A. et al (1996) Proc. Natl. Acad. Sci. 93, 5489-5494
Pouli, A. E. et al (1998) Biochem J 333(1), 193-199
Tsuboi, T. et al (2000) Curr. Biol. 10, 1307-1310
daSilvaXavier, G. et al (2000) Proc Natl Acad Sci U S A 97, 4023-4028
daSilvaXavier, G. et al (2003) Biochem. J. 371, 761-774
Leclerc, I. et al (2004) Am. J. Physiol Endocrinol. Metab 286, E1023-E1031
Leclerc, I. et al (2004) Diabetes 53, S67-S74
Richards, S. K. et al (2006) J Endocrinol. 187, 225-235
daSilvaXavier, G. et al (2004) Proc. Natl. Acad. Sci. U. S. A 101, 8319-8324
Ma, D. et al (2004) J Cin Invest 14(3),339-348.
Rutter, G. A. (2004) Diabetologia 47(11), 1861-1872
Ainscow, E. K. et al (2002) J. Physiol. (Lond) 544, 429-445
Mountjoy, P. D. et al (2007) Diabetologia 50, 168-177