Stem cell derived signals in intestinal stem cell homeostasis and cancer

The epithelia that perform vital roles throughout the body as linings and sites of exchange are constantly turned over throughout life. Cells that are lost must be replaced by stem cell division and failure to balance loss and replacement has severe consequences. An underproduction of cells could compromise tissue function and an overproduction is a hallmark of cancer (and the majority of cancers develop in epithelia). Intestinal stem cells (ISCs) are therefore tightly regulated by niche signals, tuning their behaviour to meet the needs of the tissue. While many studies have focussed on signals to stem cells from the niche, recent research has suggested that stem cells themselves may be important sources of signals.

We use the fruit fly Drosophila melanogaster to understand how ISCs are regulated. Drosophila ISC fate and the signals that regulate them are highly conserved with mammalian ISCs. Combined with the wide range of genetic tools available to manipulate them, this makes Drosophila ISCs an excellent model system. Our recent work has identified a set of secreted proteins expressed specifically in Drosophila ISCs. The majority of these have equivalent human genes, which are expressed in the human intestine. This project will characterise the function and regulation of stem cell secreted proteins in the Drosophila intestine and assess whether their functions are conserved in human ISCs.

The student will learn Drosophila genetics and a range of molecular biology techniques such as cloning and qRT-PCR. They will have full training in confocal microscopy for immunofluorescence imaging of the intestine in our Bioimaging Facility. They may also have the chance to perform electron microscopy and next generation sequencing depending on how the project develops. Through our collaborator, Rakesh Heer (Newcastle University), they will have the opportunity to translate their findings to human intestinal tissue and organoid cultures, providing a broad training in stem cell biology from flies to humans. The student will join a recently established, growing team sharing a newly refurbished lab in the Department of BIosicences, Durham University. We share lab space with four other groups working on invertebrate models of health and disease with whom we have weekly joint lab meetings. We also meet for regular seminars with the other groups in the wider ’Animal Cells and Systems’ division and have an exciting programme of department seminars that span the full range of Biosciences.

If you have any questions or would like to discuss the project in more detail please contact the supervisor ([Email Address Removed]). To apply, submit a CV and covering letter, detailing reasons for applying, to the supervisor by 31st March 2020.