Research in the Müller lab focuses on developing and applying chemical biology tools elucidate how proteins are controlled by molecular on/off switches, so-called post-translational modifications. We are particularly interested in modifications of the polypeptide backbone, and how these and more traditional modifications are involved in cellular life and death decisions. To answer these questions, we use semi-synthesis to generate ‘designer’ proteins – including the tumour suppressor p53, viral anticancer proteins and histones – allowing us to directly measure the structural and functional consequences of modifications. In parallel, we develop novel strategies to discover backbone modifications and their roles in molecular ageing and signalling. Manuel is a Wellcome Trust/Royal Society Sir Henry Dale Fellow.
People
PhD Student
PhD Student
PhD Student
PhD Student
Postdoctoral Research Associate
PhD Student
Themes
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.
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.
Protein semi-synthesis
We employ cutting edge protein semi-synthesis methods to prepare site-specifically modified proteins: chemical peptide synthesis enables the incorporation of diverse modifications and chemoselective ligation strategies permit the precise attachment of synthetic fragments to large recombinant proteins. Full-length proteins generated in this way enable us to directly measure how post-translational modifications control functional properties in biochemical, biophysical and cellular assays.
Publications
Awards
2021 Chemistry Biology Interface Division early career award: Norman Heatley Award, Royal Society of Chemistry
2016-2021 Sir Henry Dale Fellowship, Wellcome Trust and the Royal Society
People
PhD Student
PhD Student
PhD Student
PhD Student
Postdoctoral Research Associate
PhD Student
Themes
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.
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.
Protein semi-synthesis
We employ cutting edge protein semi-synthesis methods to prepare site-specifically modified proteins: chemical peptide synthesis enables the incorporation of diverse modifications and chemoselective ligation strategies permit the precise attachment of synthetic fragments to large recombinant proteins. Full-length proteins generated in this way enable us to directly measure how post-translational modifications control functional properties in biochemical, biophysical and cellular assays.
Publications
Awards
2021 Chemistry Biology Interface Division early career award: Norman Heatley Award, Royal Society of Chemistry
2016-2021 Sir Henry Dale Fellowship, Wellcome Trust and the Royal Society
Group lead
Reader in Chemical Biology
Contact us
Britannia House
7 Trinity Street – 112A
London
SE1 1DB