Signalling Dynamics in Intestinal Stem Cell Homeostasis and Ageing

Intestinal stem cells (ISCs) are tightly regulated to balance differentiation with proliferation and maintain homeostasis. However, in the ageing intestine this balance is lost resulting in the dysplasia and declining tissue function that are associated with mortality. Drosophila ISCs are regulated by the same conserved signalling pathways that regulate mammalian epithelial stem cells making them an excellent model for homeostasis and ageing.

While the major signalling pathways involved in regulation are known, the temporal dynamics of the signals and how they work together sequentially or synchronously to regulate fate are poorly understood. A major challenge in stem cell biology is that while signalling events may occur on a timescale of seconds the impact on cell fate may not be seen for many hours.

This project aims to understand the importance of signalling dynamics in stem cell regulation in vivo through three main objectives: 1. Measure signalling pathway dynamics in ISCs in vivo during homeostasis and ageing through live intravital imaging. 2. Characterise the regulatory mechanisms that drive these dynamics.

3. Manipulate dynamics to change cell fate.

Together these objectives will characterise the role of signalling dynamics in stem cell homeostasis and age-related mis-regulation in an important model system relevant to human intestinal health.