Research

We study how stem cells interpret signals from their environment to choose their fate, what mechanisms underlie fate changes and how these decisions made by single cells are coordinated with the broader environment of the tissue and organism.

Niche signals and competitiveness

We have identified 3 major conserved signalling pathways that control the competitive ability of cyst stem cells (CySCs) in the testis, these are Hedgehog (Hh), Hippo (Hpo) and Ras/MAPK. Importantly, Ras/MAPK acts in a very similar manner in Drosophila CySCs and in mouse intestinal stem cells, suggesting our work will help understand fundamental stem cell behaviours. Ras gain of function leads to intestinal tumours, and the first step involves the mutant stem cell out-competing neighbouring wild type cells.
We use live imaging to follow stem cell replacement dynamics and study how these signals affect stem cell behaviour. We are also using large-scale sequencing approaches to find transcriptional targets of each signal, and find genes that could identify competitive stem cells.

Leaving the niche: stem cell behaviour during early differentiation

Just like self-renewal and competing to remain in the niche, differentiation is an active process that requires coordination across a tissue and active signalling. We identified a signal that promotes differentiation. This is the PI3K/Tor pathway, the major regulator of cellular growth. Moreover we showed that differentiation and cell cycle exit are coordinated through changes in metabolism. We are now actively investigating how metabolism influences differentiation.

In recent work, we have also shown that differentiation is regulated post-transcriptionally and that a new translational regulation mechanism controls cell fate decisions. We seek to identify how different translational modes regulate different transcripts.

Coordinating cell metabolism with tissue and organism needs

While we tend to study cells in isolation, organisms need to coordinate cell behaviour for tissues to function. We study this coordination in the testes, where we are examining how somatic cyst cells are wired metabolically to support germ cell needs.

As well as local interactions, there are systemic signals that coordinate stem cell behaviour with the nutritional status of the animal. We study how organismal metabolism controls stem cell behaviour in the testis, and how this changes during periods of starvation.