Research Interests

Post-translational modifications of protein backbones

 

The polypeptide backbone makes up approximately 50% of every protein's mass. Originally thought to be inert, emerging evidence suggests that protein backbones are subject to a plethora of site-specific post-translational modifications. Similarly to well-studied modifications of amino acid side chains, backbone modifications can control protein structure and function. We are developing and applying a suite of chemical biology technologies to reveal when, where and how backbone modifications impact biological processes.

Post-translational modifications of protein backbones

Post-translational modifications of the polypeptide backbone.

Molecular ageing

 

Proteins are subject to spontaneous modifications, contributing to senescence phenotypes across all kingdoms of life. For example, asparagine and aspartate residues can rearrange to isoaspartate, and long-lived proteins including eye lens crystalline contain significant amounts of isoaspartate. We aim to elucidate the biochemical, biophysical and cellular mechanisms of isoaspartate formation and explore the exciting possibility that this post-translational modification is harnessed as a molecular timer in biology.

See also:

Tianze's 2020 Biochemistry paper:

DOI: 10.1021/acs.biochem.0c00502

Manuel's 2018 Biochemistry manifesto:

DOI: 10.1021/acs.biochem.7b00861

IsoAspartate as a molecular timer

Iso-aspartate formation as a molecular timer.

Post-translational modifications in cellular life & death decisions

 

We employ cutting-edge protein semi-synthesis methods to prepare site-specifically modified proteins involved in cell death which enables us to investigate how these proteins are controlled by post-translational modifications. We are particular interested in understanding how the tumour suppressor protein p53 is activated in response to cell damage.

See also:

Sofia's & Karola's 2021 Chem Sci paper:

DOI: 10.1039/D1SC00396H

p53.tif

Semi-synthesis of phospho-p53 via native chemical ligation.