Cell Biology
Our department, based on the second floor of the Sir Alexander Fleming Building at the South Kensington Campus, was established in September 2006 and forms part of the Division’s and the College’s strategic thrust for researching the molecular basis of diabetes. Our focus is on the molecular and cellular mechanisms involved in the control of insulin release and hypothalamic activity in health and disease.
The department presently comprises three PIs.
β-cell physiology
My group is interested in the molecular mechanisms by which glucose regulates the secretion of insulin both acutely and in the longer term. We are using a combination of state of the art imaging approaches and transgenic models to address these problems. Particular interests include understanding the mechanics of the secretory event itself and how this may be affected in models of Type II diabetes.
Nipkov spinning disc image capture
Individual secretory events were monitored using rapid spinning discu confocal imaging of NPY.Venus, a convenient insulin surrogate.
β-cell development
Understanding how beta cells develop from fetal pancreatic precursor cells is an important challenge which will be necessary in order to provide supplies of “artificial” beta cells for use in transplantation therapy of type I diabetes.
Hypothalamic nutrient sensing
Subsets of neurons in the ventromedial hypothalamus respond to hormones, nutrients and other stimuli to control satiety and feeding. The activity of these neurons therefore provides the potential target for drugs to control over-eating and obesity. We are dissecting the intracellular signalling pathways through which regulatory stimuli control the firing of these cells.
Imaging insulin release by total internal reflection fluorescence (TIRF)
News
Think zinc: molecular sensor could reveal zinc's role in diseases
Imperial College press release: http://www3.imperial.ac.uk/newsandeventspggrp/imperialcollege/newssummary/news_1-9-2009-16-5-1?newsid=72602
Positions Available
PhD Studentship in Cell Biology - Central control of insulin secretion: roles of AMPK and LKB1
Full scholarship, covering home/EU fees and a bursary over three years.
Applications consisting of a CV and short personal statement should be sent to Professor Guy Rutter (g.rutter@imperial.ac.uk) by 1st May 2010.
For further details:
Rutter group publications
Selected publications
Sun, G., Tarasov, A.I., McGinty, J., McDonald, A., daSilvaXavier, G., Gorman, T., Marley, A., French, P.M., Parker, H., Gribble, F., Reimann, F., Viollet, B., Leclerc, I., Rutter, G.A. Ablation of AMPKα1 and α2 from pancreatic beta cells and RIP.Cre neurons suppresses insulin release in vivo. Diabetologia, in press, (2010)
Meur, G., Simon, A., Harun, N., Dechaume, A., Bonneford, A., Virally, M., Fetita, S., Tarasov, A.I., Boesgaard, T.W., Pedersen, O., Hansen, T., Polak, M., Gautier, J-F, Froguel, P., Rutter, G. A., Vaxillaire, M. Insulin gene mutations resulting in a MODY phenotype: marked differences in clinical presentation, metabolic status and pathogenic effect through ER retention. Diabetes, In press (2010)
Vinkenborg, J.L., Bellomo, E.A., Nicolson, T.J., Koay, M.S., Merkx, M. Rutter, G.A. Accurate measurement of cytosolic free zinc concentration using eCALWY variants: a toolbox of genetically encoded FRET sensors. Nature Protocols , (2009) http://www/natureprotocols.com/2009///accurate_measurement_of_cytoso.php
Vinkenborg, J.L., Nicolson, T.J., Bellomo, E.A., Koay, M.S., Rutter, G.A.* Merkx, M. Genetically-encoded FRET sensors to monitor Zn2+ homeostasis in living cells. Nature Methods 6(10):737-40 (2009) *corresponding author http://www.nature.com/nmeth/journal/vaop/ncurrent/full/nmeth.1368.html
Lemaire, K., Ravier, M.A., Chimienti, F., Rutter G.A., Gilon, P., Veld, P. Schuit, F. Insulin crystallisation depends on zinc transporter ZnT8 expression, but is not required for normal glucose homeostasis in mice. Proc Natl Acad Sci, 106 (35): 14872-14877 (2009) http://www.pnas.org/content/106/35/14872.full
Lerner, R.G., Depatie, C. Rutter G.A., Screaton R., Balthasar, N. A role for the CREB coactivator TORC2 in the hypothalamic mechanisms linking glucose-sensing with gene regulation. Embo Rep 10(10):1175-81 (2009) http://www.nature.com/embor/journal/vaop/ncurrent/full/embor2009177.html
Nicolson, T.J., Bellomo, E.A., Wijesekara, N., Loder, M.K., Baldwin, J.M., Gyulkhandanyan, A.V., Koshin, V., Tarasov, A.I., Carzaniga, R., Kronenberger, K., Taneja, T.K., da Silva Xavier, G., Libert, S., Froguel, P., Scharfmann, R., Stetsyuk, V., Ravassard, P., Parker, H., Gribble, F.M., Reimann, F., Sladek, R., Hughes, S.J., Johnson, P.R.V., Massebouef, M., Burcelin, R. Baldwin, S.A., Liu, M.m Lara-Lemus, R., Arvan, P., Schuit, F.C., Wheler, M.B., Chiemienti, F., Rutter, G.A. Insulin storage and glucose homeostasis in mice null for the granuel zinc transporter ZnT8 and studies of the type 2 diabetes-associated varients Diabetes, 58(9):2070-83 (2009) http://diabetes.diabetesjournals.org/content/58/9/2070.full
Meur, G., Simon, A., Harun, N., Dechaume, A., Bonneford, A., Virally, M., Fetita, S., Tarasov, A.I., Boesgaard, T.W., Pedersen, O., Hansen, T., Polak, M., Gautier, J-F, Froguel, P., Rutter, G. A., Vaxillaire, M. Insulin gene mutations resulting in a MODY phenotype: marked differences in clinical presentation, metabolic status and pathogenic effect through ER retention. Diabetes, In press [IF= 8.398] (2009)
Noordeen, N., Khera, T.K., Sun, G., Longbottom, E.R., da Silva Xavier, G., Rutter, G.A., Leclerc, I., ChREBP i a negative regulator of ARNT/HIF-1β gene expression in pancreatic islet β-cells. Diabetes, in press (2009)
Vinkenborg, J.L., Bellomo, E.A., Nicolson, T.J., Koay, M.S., Merkx, M. Rutter, G.A. Accurate measurement of cytosolic free zinc concentration using eCALWY variants: a toolbox of genetically encoded FRET sensors. Nat Protocols [IF=4.1], in press 2009) http://www/natureprotocols.com/2009/09/22/accurate_measurement_of_cytoso.php
Vinkenborg, J.L., Nicolson, T.J., Bellomo, E.A., Koay, M.S., Rutter, G.A.* Merkx, M. Genetically-encoded FRET sensors to monitor Zn2+ homeostasis in living cells. Nat Methods in press (2009) *corresponding author http://www.nature.com/nmeth/journal/vaop/ncurrent/full/nmeth.1368.html
McDonald, A., Fogarty, S., Leclerc, I., Hill, E., Hardie, D.G., and Rutter, G.A. Control of insulin granule dynamics by AMPK-dependent KLC1 phosphorylation. Islets, in press (2009)
Lemaire, K., Ravier, M.A., Chimienti, F., Rutter G.A., Gilon, P., Veld, P. Schuit, F. Insulin crystallisation depends on zinc transporter ZnT8 expression, but is not required for normal glucose homeostasis in mice. Proc Natl Acad Sci, in press (2009) http://www.pnas.org/content/106/35/14872.full
Lerner, R.G., Depatie, C. Rutter G.A., Screaton R., Balthasar, N. A role for the CREB coactivator TORC2 in the hypothalamic mechanisms linking glucose-sensing with gene regulation. Embo Rep in press (2009) http://www.nature.com/embor/journal/vaop/ncurrent/full/embor2009177.html
Nicolson, T.J., Bellomo, E.A., Wijesekara, N., Loder, M.K., Baldwin, J.M., Gyulkhandanyan, A.V., Koshin, V., Tarasov, A.I., Carzaniga, R., Kronenberger, K., Taneja, T.K., da Silva Xavier, G., Libert, S., Froguel, P., Scharfmann, R., Stetsyuk, V., Ravassard, P., Parker, H., Gribble, F.M., Reimann, F., Sladek, R., Hughes, S.J., Johnson, P.R.V., Massebouef, M., Burcelin, R. Baldwin, S.A., Liu, M.m Lara-Lemus, R., Arvan, P., Schuit, F.C., Wheler, M.B., Chiemienti, F., Rutter, G.A. Insulin storage and glucose homeostasis in mice null for the granuel zinc transporter ZnT8 and studies of the type 2 diabetes-associated varients Diabetes, Jun 19 [EPub ahead of print] (2009) http://diabetes.diabetesjournals.org/content/58/9/2070.full
da Silva Xavier, G., Loder, M., McDonald, A., Carzaniga, R., Kronenberger, K., Barg, S. and Rutter, G.A. TCF7L2 regulates late events in insulin secretion from pancreatic islet β-cells. Diabetes, 58 (4): 894-905 (2009) http://diabetes.diabetesjournals.org/content/58/4/894.full
Tarasov, A.I., Nicolson, T., Riveline, J-P, Taneja, T.K., Baldwin, S.A., Baldwin, J., Charpentier, G., Gautier, J-F, Froguel, P, Vaxillaire, M, Rutter, G.A. A rare mutation in ABCC8/SUR1 leading to altered KATP channel activity and β-cell glucose sensing is associated with type 2 diabetes mellitus in adults. Diabetes. 57(6), 1595-1604 (2008) http://diabetes.diabetesjournals.org/content/57/6/1595.full
daSilvaXavier, G, Rutter, J., and Rutter G.A. Involvement of PAS kinase in the stimulation of preproinsulin and pancreatic duodenum homeobox-1 gene expression by glucose. Proc Natl Acad Sci. 101(22), 8319-8324 (2004) http://www.pnas.org/content/101/22/8319.full
daSilva Xavier, G., Leclerc, I., Salt, I. Doiron, B., Hardie, D.G., Kahn, A., Rutter, G.A. Role of AMP-activated protein kinase in the regulation by glucose of islet b-cell gene expression Proc. Natl. Acad. Sci 97, 4023-4028 (2000) http://www.pnas.org/content/97/8/4023.full
Jouaville, L.S, Bastianutto, C., Pinton, P., Rutter, G.A. Rizzuto, R. Regulation of mitochondrial ATP synthesis by calcium: evidence for a long term, Ca2+-triggered, mitochondrial activation. Proc. Natl. Acad. Sci. 96, 13807-13812 (1999) http://www.pnas.org/content/96/24/13807.full
Rutter, G.A., Burnett, P. Rizzuto, R., Brini, M., Pozzan, T., Tavaré, J.M. and Denton, R.M. Digital imaging of intramitochondrial Ca2+ with recombinant targeted aequorin: significance for the regulation of pyruvate dehydrogenase activity. Proc. Natl. Acad. Sci. 93, 5489-5494 (1996) http://www.pnas.org/content/93/11/5489.full.pdf+html
