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Drosophila as a model to study local and systemic regulation of intestinal homeostasis


Cell Biology of Cancer

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Dr J Cordero No more applications being accepted Funded PhD Project (European/UK Students Only)

About the Project

Long-term maintenance of self-renewing epithelia relies on tight coordination of tissue intrinsic and systemic signals. How these signals influence each other to preserve tissue homeostasis and organismal health is unclear.

The adult intestine is a major organ with vital physiological, endocrine, immune and metabolic roles. These functions are achieved by specialized cells such as absorptive enterocytes and secretory enteroendocrine cells, which are generated and replenished by intestinal stem cells. Additionally, the intestine interacts remotely or directly with multiple tissues and organs.

Work in our laboratory is devoted to understanding cellular and molecular mechanisms regulating intestinal stem cells proliferation during tissue homeostasis, regeneration and tumourigenesis, through the use of Drosophila and mammalian model systems (1). We are also interested in understanding how the intestine interacts with other tissues and organs to maintain whole-body health and how these interactions are deregulated in cancer (2, 3). Our research has direct implications in health and disease as it can aid the identification of approaches to restore intestinal regeneration as well as the development of therapies aimed to prevent malignant transformation in the intestine and alleviate the systemic consequences of intestinal malfunction.

Projects in the lab that will be available for development through this studentship include:

1-Understanding the role and regulation of gut-associated tissues such as the vasculature and enteric neurons in intestinal stem cell proliferation.

2-Studying local and systemic functions of enteroendocrine cells during intestinal regeneration.

These projects will primarily entail work on adult Drosophila, followed by translation of key results into a suitable mammalian paradigm, mainly mouse intestinal models

The Cancer Research UK Beatson Institute in Glasgow is one of the world-leading centres for cancer research. The Institute provides an outstanding research environment, underpinned by state-of-the-art core services and advanced technologies with special emphasis on imaging, metabolomics and in vivo models of cancer.

To apply, please click on the ’Visit Website’ button, which will take you to the Beatson Institute website where you should fill in the application form. Please do not email your CV.

References

• Parvy JP1, Yu Y, Dostalova A, Kondo S, Kurjan A, Bulet P, Lemaitre B, Vidal M, Cordero JB1. The antimicrobial peptide Defensin cooperates with Tumour Necrosis Factor to drive tumour cell death in Drosophila. Elife. 2019 Jul 30;8. pii: e45061. doi: 10.7554/eLife.45061.

• Johansson J*, Naszai M*, Hodder M, Pickering K, Miller BW, Ridgway RA, Yu Y, Peschard P, Brachmann B, Campbell AD, Cordero, JB1, Sansom, OJ1. RAL GTPases drive intestinal stem cell function and regeneration through internalization of WNT signalosomes. Cell Stem Cell. Apr 4;24(4):592-607.e7. doi: 10.1016/j.stem.2019.02.002.

• Scopelliti A1*, Bauer C*, Yu Y, Zhang T, Krüspig B, Murphy DJ, Vidal M, Maddocks OK, Cordero JB1. A neuronal relay mediates a nutrient responsive gut/fat body axis regulating energy homeostasis in adult Drosophila. Cell Metab. Oct 15. pii: S1550-4131(18)30629-6. doi: 10.1016/j.cmet.2018.09.021.


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