Function of post-translational modifications of protein backbones in signalling and molecular ageing

The majority of tasks inside living cells are performed by tiny molecular machines, called proteins. Most proteins are regulated by chemical on/off switches. Malfunction of these switches can have disastrous consequences for the wellbeing of individual cells and entire organisms.

I am fascinated by a class of protein switches that respond to molecular wear and tear to signal for repair processes. However, investigating such processes is extremely challenging due to a lack of means to efficiently detect which of over 30,000 different proteins in a cell are affected by ageing, and our inability to age proteins in a controlled manner.

I propose to develop a suite of chemical biology technologies to illuminate how molecular wear and tear impacts senescence of cells and entire organisms. I will design molecular scalpels that precisely cut proteins only at sites of ablation. This will allow me to identify proteins that are susceptible to ageing. I will chemically install artificially aged components into otherwise young proteins and measure how old components affect the structure and function of molecular machines.

I aim to identify senescence sensors and delineate how they operate in healthy cells and might malfunction in diseases.