Characterisation of Niche-derived signals controlling Intestinal Stem Cell proliferation and gut homeostasis

Hovedområde:Cell biology
Målgruppe:Biology, Molecular Biomedicine, Biochemistry

Gut physiology and immunity are regulated by multiple signals emanating from the external environment (e.g. microbial derivatives) and other organs including the brain and the adipose tissues. Despite the physiological divergence between insects and mammals, studies have shown that flies represent a model that is well suited for studying intestinal stem cell physiology during ageing, stress, and infection. At steady-state turnover rates, the intestine undergoes complete self-renewal every 4-5 days, a process which is highly accelerated in response to damage of the gut epithelium. This capacity for self-renewal relies on the proliferative activity of the intestinal stem cells (ISC), which is tightly coupled with cell loss to maintain intestinal homeostasis. Failure to balance ISC proliferation with cell loss can trigger a number of gut-related pathologies including colorectal cancer. ISC proliferation is controlled by multiple local signals released from neighboring cell populations, the ISC niche. The ISC niche consists of the enterocytes (ECs) making up the majority of the gut epithelium, the enteroendocrine (EE) cells, and the visceral muscles (VMs) that surround the gut. To identify signals emanating from the ISC niche that control ISC proliferation, we recently conducted a large-scale RNAi-based genetic screen in adult flies, where we knocked down 800 secreted peptides specifically in the ECs, the EE cells, or the VMs. We screened for signals that are important for maintaining gut barrier function under homeostatic conditions and/or signals required for the ISC-mediated regenerative growth response induced by bacterial assaults. We are particularly interested in the stress-induced signals promoting ISC-dependent tissue self-renewal, since the same signals tend to initiate ISC tumorigenesis in predisposed individuals.

The proposed Master projects will be centered around the characterization of specific candidate genes and their roles in controlling ISC proliferation under homeostatic and stress conditions and will involve a mix of techniques including molecular biology, imaging and genetics. The work will take place at the Cell and Neurobiology Section at the institute of Biology. If this sounds interesting to you, let us know, and we can explain you in more details. Also check out our homepage:

As we are externally affiliated with DanStem, you will be participating in weekly meetings at SUND:

Anvendte metoder:Genetics, Survival assays, gut dissections and measurements of Stem Cell proliferation, metabolic measurements, qPCRs, cloning, generation of transgenic flies, Immuno-blotting, confocal microscopy
Keywords:Stem Cells, Drosophila, Gut, Physiology, Regeneration
Vejleder(e): Ditte Andersen, Julien Colombani