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Islet Biology Laboratory

pancreatic islets, beta cells, transplantation...

A section of a pancreatic islet from a
mouse under the confocal microscope

Research Summary

Our research focuses on the islets of Langerhans in the pancreas, which house the only cell type capable of producing insulin – the beta cell. In particular, we are interested in the molecules that are involved in intercellular communication within the islet during high glucose, inflammatory assaults, revascularisation and transplantation. We have close collaborations with the Australian Islet Consortium, which is running the first Australian clinical trial for islet transplantation as a treatment for Type 1 diabetes.

Research Projects

We are investigating how beta cells ‘talk’ to neighbouring vascular endothelial cells which may up tiny pancreatic blood vessels. If we can identify the important soluble factors or cell surface molecules involved, we may find new targets for diabetes. Techniques include RNAseq transcriptome analysis, proteomics, cell culture and magnetic bead-based separation.

This is a collaborative project with Assoc Prof Damien Keating and Dr Heshan Peiris (Molecular and Cellular Neuroscience Laboratory), examining the importance of an endogenous calcineurin inhibitor for beta cell survival and function. Techniques include confocal microscopy, tissue culture, ELISA and RT-PCR.

This project is run in conjunction with the Centre for Clinical and Experimental Transplantation (Central and Northern Adelaide Renal and Transplantation Service, www.ccet.org.au/about-us) and aims to improve the survival and function of pancreatic islets during transplantation. Techniques include cell culture, microsurgery and experimental gene therapy.

This project is run in collaboration with Dr Claudine Bonder (Centre for Cancer Biology, SA Pathology). We are investigating the potential of vascular progenitor cells (the building blocks of blood vessels) to speed the repair and revascularisation of transplanted islets. Techniques include primary cell isolation, angiogenesis assays, Q-PCR and siRNA knock-down techniques.

In collaboration with Dr Michael Jackson (Immunology, Allergy & Arthritis) we are investigating the potential of fibroblast growth factor-based proteins in improving pancreatic islet survival. Techniques include cell culture, ELISA and Q-PCR.

Selected Publications

Coleman MA, Jessup CF, Bridge JA, Overgaard NH, Penko D, Walters S, Borg DJ, Galea R, Forbes JM, Thomas R, Coates PT, Grey ST, Wells JW, Steptoe RJ (2016) Antigen-encoding bone marrow terminates islet-directed memory CD8+ T-cell responses to alleviate islet transplant rejection. Diabetes, 65(5):1328-1340

 

Peiris H, Duffield MD, Fadista J, Jessup CF, Kashmir V, Genders AJ, McGee SL, Martin AM, Saiedi M, Morton N, Carter R, Cousin MA, Kokotos AC, Oskolkov N, Volkov P, Hough TA, Fisher EM, Tybulewicz VL, Busciglio J, Coskun PE, Becker A, Belichenko PV, Mobley WC, Ryan MT, Chan JY, Laybutt DR, Coates PT, Yang S, Ling C, Groop L, Pritchard MA, Keating DJ (2016) A Syntenic Cross Species Aneuploidy Genetic Screen Links RCAN1 Expression to β-Cell Mitochondrial Dysfunction in Type 2 Diabetes. PLoS Genetics, 12(5):e1006033

 

Raghupathi R, Jessup CF, Lumsden AL and Keating DJ (2016) Fusion pore size limits 5-HT release from single enterochromaffin cell vesicles. Journal of Cellular Physiology, 231(7):1593-600

 

Penko D, Rojas-Canales D, Mohanasundaram D, Peiris HS, Sun WY, Drogemuller CJ, Coates PTH, Bonder CS and Jessup CF (2015) Endothelial progenitor cells influence islet engraftment and beta cell function. Cell Transplantation, 24(1):37-48

 

Canlas J, Holt P, Carroll A, Rix S, Ryan P, Davies L, Matusica D, Pitson SM, Jessup CF, Gibbins IL, Haberberger RV (2015) Sphingosine kinase 2-deficiency mediated changes in spinal pain processing. Frontiers in Molecular Neuroscience, 8:29

 

Peiris H, Dubach D, Jessup CF, Unterweger P, Raghupathi R, Muyderman H, Zanin MP, Mackenzie K, Pritchard MA, Keating DJ (2014) RCAN1 regulates mitochondrial function and increases susceptibility to oxidative stress in mammalian cells. Oxidative Medicine & Cellular Longevity, 2014:520316

 

Peiris HS, Bonder CS, Keating DJ, Coates PTH and Jessup CF (2014) The beta cell/EC axis: how do islet cells and endothelial cells talk to each other? Review. Diabetes, 63(1):3-11

 

Hughes A, Mohanasundaram D, Kireta S, Jessup CF, Drogemuller CJ and Coates PTH (2013) An insulin-like growth factor-II (IGF-II) anti-apoptotic strategy improves islet cell survival for transplantation. Transplantation, 95(5):671-678

 

Appleby SL, Jessup CF, Mortimer LA, Kirk K, Brereton HM, Coster DJ, Tan CK and Williams KA (2013) Expression of an anti-CD4 single chain antibody fragment from the donor cornea can prolong corneal allograft survival in inbred rats. British Journal of Ophthalmology, 97(1):101-5

 

Rojas-Canales D, Krishnan R, Jessup CF, Coates PTH (2012) Early exposure of interferon-gamma inhibits signal transducer and activator of transcription-6 signalling and nuclear factor kB activation in a short-term monocyte-derived dendritic cell culture promoting ‘FAST’ regulatory dendritic cells. Clinical and Experimental Immunology, 167(3):447-58

 

Peiris H, Raghupathi R, Jessup CF, Zanin MP, Mohanasundaram D, Mackenzie KD, Chataway T, Clarke JN, Brealey J, Coates PT, Pritchard MA, Keating DJ (2012) Increased expression of the glucose-responsive gene, RCAN1, causes hypoinsulinemia, β-cell dysfunction, and diabetes. Endocrinology, 153(11):5212-21

 

Fernandes RA, Shore DA, Vuong MT, Yu C, Zhu X, Pereira-Lopes S, Brouwer H, Fennelly JA, Jessup C, Evans EJ, Wilson IA, Davis SJ (2012) T Cell Receptors are Structures Capable of Initiating Signaling in the Absence of Large Conformational Rearrangements. Journal of Biological Chemistry, 287(16):13324-35

 

Penko D, Mohanasundaram D, Sen S, Drogemuller C, Mee C, Bonder CS, Coates PT, Jessup CF (2011) Incorporation of endothelial progenitor cells into mosaic pseudoislets. Islets, 3(3):73-9

 

Jessup CF, Bonder CS, Pitson SM, Coates PTH (2011) The sphingolipid rheostat: a potential target for improving pancreatic islet survival and function. Endocrine, Metabolic & Immune Disorders - Drug Targets, 11(4):262-72

 

Mohanasundaram D, Drogemuller C, Brealey J, Jessup CF, Milner C, Murgia C, Lang CJ, Milton A, Zalewski PD, Russ GR, Coates PT (2011) Ultrastructural analysis, zinc transporters, glucose transporters and hormone expression in new world primate (Callithrix jacchus) and human pancreatic islets. General and Comparative Endocrinology, 174(2):71-9

 


Investigator

  • Claire Jessup, VC Research Fellow, BBiotech(Hons), PhD


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