Gut/body interactions in intestinal regeneration and tumourigenesis

Prof Julia Cordero & Dr Saverio Tardito

APPLY HERE

Labs: Local and Systemic Functions of the Intestine in Health and Disease and Oncometabolism
Duration: 4 years, starting Oct 2023
Closing Date: 6th January 2023

Project Description

The adult intestine is a major barrier epithelium and coordinator of multi-organ functions. As such, disruptions to intestinal homeostasis have profound impact in gut and whole organismal health. Stem cells constantly repair the intestinal epithelium by adjusting their proliferation and differentiation to tissue intrinsic as well as micro- and macro-environmental signals. How these signals integrate to control intestinal and whole-body homeostasis is largely unknown. Addressing this gap in knowledge is central to an improved understanding of intestinal pathophysiology and its systemic consequences.
Combining Drosophila and mammalian model systems the Cordero laboratory has discovered fundamental mechanisms driving intestinal regeneration and tumourigenesis and outlined complex inter-organ signaling regulating health and disease. Building up on these findings, this PhD project aims to.

1. Characterise systemic outputs associated with the process of intestinal regeneration and tumourigenesis, including metabolic and behavioural changes.
2. Identify the intestinal signals and mechanisms driving such whole-body changes.
3. Characterise the functional significance of changes identified in Aim 1, to intestinal health and tumourigenesis.

For informal enquiries or further details on the project, please contact Prof Julia Cordero (Julia.Cordero@glasgow.ac.uk)

APPLY HERE

Publications

Medina A, Bellec K, Polcowñuk S, Cordero JB. Investigating local and systemic intestinal signalling in health and disease with Drosophila. Dis Model Mech. 2022; 15:dmm049332

Nászai M, Bellec K, Yu Y, Román-Fernández A, Sandilands E, Johansson J, Campbell AD, Norman JC, Sansom OJ, Bryant DM, Cordero JB. RAL GTPases mediate EGFR-driven intestinal stem cell proliferation and tumourigenesis. Elife. 2021 Jun 7;10:e63807

Perochon J, Yu Y, Aughey GN, Medina AB, Southall TD, Cordero JB. Dynamic adult tracheal plasticity drives stem cell adaptation to changes in intestinal homeostasis in Drosophila. Nat Cell Biol. 2021; 23:485–496

Johansson J, Naszai M, Hodder M, Pickering K, Miller BW, Ridgway RA, Yu Y, Peschard P, Brachmann B, Campbell AD, Cordero, JB1, Sansom, OJ. RAL GTPases drive intestinal stem cell function and regeneration through internalization of WNT signalosomes. Cell Stem Cell. Apr 4;24(4):592-607.e7. Commentary in Cell Stem Cell 2019 Apr 4;24:499-500.

Scopelliti A, Bauer C, Yu Y, Zhang T, Krüspig B, Murphy DJ, Vidal M, Maddocks OK, Cordero JB. A neuronal relay mediates a nutrient responsive gut/fat body axis regulating energy homeostasis in adult Drosophila. Cell Metab. 2019 Feb 5;29:269-284.e10.

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