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OptoBETA SIGNED

Multicellular regulation of insulin secretion from pancreatic islets

Total Cost €

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EC-Contrib. €

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Partnership

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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 UK (BIRMINGHAM) coordinator 1˙681˙468.00

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 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

year authors and title journal last update
List of publications.
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 β-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 Romanò, 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 β 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 Münzberg, David A. Jacobson, Prasad V. Katakam, David J. Hodson, Ernesto Bernal-Mizrachi, Andrea Zsombok, Franck Mauvais-Jarvis
Androgen excess in pancreatic β 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-Röder
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 β-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 M’Kadmi, Jean-Louis Baneres, Jacky Marie, Alejandra Tomas, Dirk Trauner, Anja Hoffmann-Röder, 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 β-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 β-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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