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OptoBETA SIGNED

Multicellular regulation of insulin secretion from pancreatic islets

Total Cost €

EC-Contrib. €

Partnership

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Outcomes and
results

OptoBETA project word cloud

Explore the words cloud of the OptoBETA project. It provides you a very rough idea of what is the project "OptoBETA" about.

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Project "OptoBETA" data sheet

The following table provides information about the project.

Coordinator	THE UNIVERSITY OF BIRMINGHAM Organization address address: Edgbaston city: BIRMINGHAM postcode: B15 2TT website: www.bham.ac.uk contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.
Coordinator Country	United Kingdom [UK]
Project website	https://www.birmingham.ac.uk/staff/profiles/metabolism-systems/hodson-david.aspx
Total cost	1˙681˙468 €
EC max contribution	1˙681˙468 € (100%)
Programme	1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
Code Call	ERC-2016-STG
Funding Scheme	ERC-STG
Starting year	2017
Duration (year-month-day)	from 2017-06-01 to 2022-05-31

Partnership

Take a look of project's partnership.

#	participants	country	role	EC contrib. [€]
1	THE UNIVERSITY OF BIRMINGHAM THE UNIVERSITY OF BIRMINGHAM Organization address address: Edgbaston city: BIRMINGHAM postcode: B15 2TT website: www.bham.ac.uk contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.	UK (BIRMINGHAM)	coordinator	1˙681˙468.00

Map

Project objective

Type 2 diabetes mellitus, one of the major healthcare challenges of our time, is characterized by failure of beta cells to functionally adapt to increased peripheral insulin resistance. The resulting chronic elevations in blood glucose concentration are associated with heart, kidney, liver, nerve and retinal disease, as well as cancer. Here, by combining novel optogenetic, photopharmacological and innovative imaging approaches, we aim to unravel the complexity underlying the multicellular regulation of insulin secretion from islets of Langerhans during health and disease. In particular, we will examine a role for privileged pacemakers/hubs in orchestrating population responses to stimuli, identify what makes these specialized cells unique at the RNA/protein level, and understand how they contribute to islet development and failure. Furthermore, we will address whether the intraislet regulation of insulin secretion operates in vivo to determine glucose homeostasis, focusing on the neural-endocrine interface. Lastly, the mechanisms underlying islet cross-talk will be investigated directly in situ within the pancreas of living mice, paying close attention to the roles of the vasculature and secreted factors. As such, these studies should unveil a new route for restoration of insulin secretion in man, as well as provide the foundation for the de novo construction of islets for transplantation.

Publications

List of publications.
year	authors and title	journal	last update
2019	Sophie R. Sayers, Rebecca L. Beavil, Nicholas H. F. Fine, Guo C. Huang, Pratik Choudhary, Kamila J. Pacholarz, Perdita E. Barran, Sam Butterworth, Charlotte E. Mills, J. Kennedy Cruickshank, Marta P. Silvestre, Sally D. Poppitt, Anne-Thea McGill, Gareth G. Lavery, David J. Hodson, Paul W. Caton Structure-functional changes in eNAMPT at high concentrations mediate mouse and human beta cell dysfunction in type 2 diabetes published pages: , ISSN: 0012-186X, DOI: 10.1007/s00125-019-05029-y	Diabetologia	2019-12-16
2019	Rebecca J. Thompson, Alice Fletcher, Katie Brookes, Hannah Nieto, Mohammed M. Alshahrani, Jonathan W. Mueller, Nicholas H.F. Fine, David J. Hodson, Kristien Boelaert, Martin L. Read, Vicki E. Smith, Christopher J. McCabe Dimerization of the Sodium/Iodide Symporter published pages: 1485-1498, ISSN: 1050-7256, DOI: 10.1089/thy.2019.0034	Thyroid 29/10	2019-12-16
2019	Daniela Nasteska, Katrina Viloria, Lewis Everett, David J. Hodson Informing Î²-cell regeneration strategies using studies of heterogeneity published pages: S49-S59, ISSN: 2212-8778, DOI: 10.1016/j.molmet.2019.06.004	Molecular Metabolism 27	2019-12-16
2019	Siew H. Yip, Nicola RomanÃ², Papillon Gustafson, David J. Hodson, Eloise J. Williams, Ilona C. Kokay, Agnes O. Martin, Patrice Mollard, David R. Grattan, Stephen J. Bunn Elevated Prolactin during Pregnancy Drives a Phenotypic Switch in Mouse Hypothalamic Dopaminergic Neurons published pages: 1787-1799.e5, ISSN: 2211-1247, DOI: 10.1016/j.celrep.2019.01.067	Cell Reports 26/7	2019-12-16
2019	Michael W. O\'Reilly, Connar S.J. Westgate, Catherine Hornby, Hannah Botfield, Angela E. Taylor, Keira Markey, James L. Mitchell, William J. Scotton, Susan P. Mollan, Andreas Yiangou, Carl Jenkinson, Lorna C. Gilligan, Mark Sherlock, James Gibney, Jeremy W. Tomlinson, Gareth G. Lavery, David J. Hodson, Wiebke Arlt, Alexandra J. Sinclair A unique androgen excess signature in idiopathic intracranial hypertension is linked to cerebrospinal fluid dynamics published pages: , ISSN: 2379-3708, DOI: 10.1172/jci.insight.125348	JCI Insight	2019-12-16
2017	Zenobia B. Mehta, Natalie R. Johnston, Marie-Sophie Nguyen-Tu, Johannes Broichhagen, Peter Schultz, Dean P. Larner, Isabelle Leclerc, Dirk Trauner, Guy A. Rutter, David J. Hodson Remote control of glucose homeostasis in vivo using photopharmacology published pages: , ISSN: 2045-2322, DOI: 10.1038/s41598-017-00397-0	Scientific Reports 7/1	2019-05-14
2017	Jaimini Cegla, Ben J Jones, James V Gardiner, David J Hodson, Thomas Marjot, Emma R McGlone, Tricia M Tan, Stephen R Bloom RAMP2 Influences Glucagon Receptor Pharmacology via Trafficking and Signaling published pages: 2680-2693, ISSN: 0013-7227, DOI: 10.1210/en.2016-1755	Endocrinology 158/8	2019-05-14
2017	Ryan K. Mitchell, Marie-Sophie Nguyen-Tu, Pauline Chabosseau, Rebecca M. Callingham, Timothy J. Pullen, Rebecca Cheung, Isabelle Leclerc, David J. Hodson, Guy A. Rutter The transcription factor Pax6 is required for pancreatic Î² cell identity, glucose-regulated ATP synthesis, and Ca 2+ dynamics in adult mice published pages: 8892-8906, ISSN: 0021-9258, DOI: 10.1074/jbc.M117.784629	Journal of Biological Chemistry 292/21	2019-05-14
2018	Guadalupe Navarro, Camille Allard, Jamie J. Morford, Weiwei Xu, Suhuan Liu, Adrien J.R. Molinas, Sierra M. Butcher, Nicholas H.F. Fine, Manuel Blandino-Rosano, Venkata N. Sure, Sangho Yu, Rui Zhang, Heike MÃ¼nzberg, David A. Jacobson, Prasad V. Katakam, David J. Hodson, Ernesto Bernal-Mizrachi, Andrea Zsombok, Franck Mauvais-Jarvis Androgen excess in pancreatic Î² cells and neurons predisposes female mice to type 2 diabetes published pages: , ISSN: 2379-3708, DOI: 10.1172/jci.insight.98607	JCI Insight 3/12	2019-05-14
2017	Tom Podewin, Johannes Broichhagen, Christina Frost, Dieter Groneberg, Julia Ast, Helena Meyer-Berg, Nicholas H. F. Fine, Andreas Friebe, Martin Zacharias, David J. Hodson, Dirk Trauner, Anja Hoffmann-RÃ¶der Optical control of a receptor-linked guanylyl cyclase using a photoswitchable peptidic hormone published pages: 4644-4653, ISSN: 2041-6520, DOI: 10.1039/c6sc05044a	Chemical Science 8/6	2019-04-18
2017	Ben J. Jones, Rosario Scopelliti, Alejandra Tomas, Stephen R. Bloom, David J. Hodson, Johannes Broichhagen Potent Prearranged Positive Allosteric Modulators of the Glucagon-like Peptide-1 Receptor published pages: 501-505, ISSN: 2191-1363, DOI: 10.1002/open.201700062	ChemistryOpen 6/4	2019-04-18
2018	Sharan Janjuha, Sumeet Pal Singh, Anastasia Tsakmaki, S Neda Mousavy Gharavy, Priyanka Murawala, Judith Konantz, Sarah Birke, David J Hodson, Guy A Rutter, Gavin A Bewick, Nikolay Ninov Age-related islet inflammation marks the proliferative decline of pancreatic beta-cells in zebrafish published pages: , ISSN: 2050-084X, DOI: 10.7554/eLife.32965	eLife 7	2019-04-18
2018	James A. Frank, Johannes Broichhagen, Dmytro A. Yushchenko, Dirk Trauner, Carsten Schultz, David J. Hodson Optical tools for understanding the complexity of Î²-cell signalling and insulin release published pages: 721-737, ISSN: 1759-5029, DOI: 10.1038/s41574-018-0105-2	Nature Reviews Endocrinology 14/12	2019-04-18
2018	Daniela Nasteska, David J Hodson The role of beta cell heterogeneity in islet function and insulin release published pages: R43-R60, ISSN: 0952-5041, DOI: 10.1530/JME-18-0011	Journal of Molecular Endocrinology 61/1	2019-04-18
2018	Tom Podewin, Julia Ast, Johannes Broichhagen, Nicholas H. F. Fine, Daniela Nasteska, Philipp Leippe, Manuel Gailer, Teresa Buenaventura, Nisha Kanda, Ben J. Jones, Celine Mâ€™Kadmi, Jean-Louis Baneres, Jacky Marie, Alejandra Tomas, Dirk Trauner, Anja Hoffmann-RÃ¶der, David J. Hodson Conditional and Reversible Activation of Class A and B G Protein-Coupled Receptors Using Tethered Pharmacology published pages: 166-179, ISSN: 2374-7943, DOI: 10.1021/acscentsci.7b00237	ACS Central Science 4/2	2019-04-18
2017	James Allen Frank, Dmytro A. Yushchenko, Nicholas H. F. Fine, Margherita Duca, Mevlut Citir, Johannes Broichhagen, David J. Hodson, Carsten Schultz, Dirk Trauner Optical control of GPR40 signalling in pancreatic Î²-cells published pages: 7604-7610, ISSN: 2041-6520, DOI: 10.1039/c7sc01475a	Chem. Sci. 8/11	2019-04-18
2018	Richard K.P. Benninger, David J. Hodson New Understanding of Î²-Cell Heterogeneity and In Situ Islet Function published pages: 537-547, ISSN: 0012-1797, DOI: 10.2337/dbi17-0040	Diabetes 67/4	2019-04-18
2018	Richard K. P. Benninger, Craig Dorrell, David J. Hodson, Guy A. Rutter The Impact of Pancreatic Beta Cell Heterogeneity on Type 1 Diabetes Pathogenesis published pages: , ISSN: 1534-4827, DOI: 10.1007/s11892-018-1085-2	Current Diabetes Reports 18/11	2019-04-18
2018	Kate E.R. Hollinshead, Haydn Munford, Katherine L. Eales, Chiara Bardella, Chunjie Li, Cristina Escribano-Gonzalez, Alpesh Thakker, Yannic Nonnenmacher, Katarina Kluckova, Mark Jeeves, Robert Murren, Federica Cuozzo, Dan Ye, Giulio Laurenti, Wei Zhu, Karsten Hiller, David J. Hodson, Wei Hua, Ian P. Tomlinson, Christian Ludwig, Ying Mao, Daniel A. Tennant Oncogenic IDH1 Mutations Promote Enhanced Proline Synthesis through PYCR1 to Support the Maintenance of Mitochondrial Redox Homeostasis published pages: 3107-3114, ISSN: 2211-1247, DOI: 10.1016/j.celrep.2018.02.084	Cell Reports 22/12	2019-04-18

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