Ageing & Stress Response

In Simple Terms

When a cell meets stress, such as running short of nutrients or too much light, it reacts within seconds by changing which proteins it makes. It pauses most of its message reading and switches to the instructions it needs to survive. This rapid response is largely controlled at the translation step, before the message is even converted into protein. As cells age, this quick reflex becomes slower and less accurate, which may be part of why ageing tissues cope less well with challenges. We study how the reflex works when it is healthy, and how it drifts over a lifetime.

The Science

Using TCP-seq to capture ribosome and pre-initiation complex positions before and after a stress, together with STE modelling and RISER for real-time enrichment of RNA classes during sequencing, we resolve the earliest translational events that reprogramme protein synthesis. Yeast under glucose starvation provides a tractable model of acute initiation-phase control, and we extend the same framework to light stress and recovery in plants and to translational changes associated with cell ageing. The goal is a mechanistic account of how initiation control sets the speed and fidelity of the stress response, and how that control degrades with age.

Team

• Dr Nikolay ShirokikhLead
• Prof Alice CleynenLead
• Dr Danielle RudlerSenior Postdoctoral Staff Scientist

Tools & Methods

Key Publications

All publications