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

Year of award: 2016


  • Dr Manuel Mueller

    King's College London

Project summary

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.