LIDo banner

Apply now

Find out more about the different routes to entry and our eligibility criteria

Dissecting p53 signaling with Chemical Biology

Manual Muller research image

The tumor suppressor protein p53 plays a central role in orchestrating the cellular response to genotoxic damage. Specifically, p53 can induce DNA damage repair processes or in extreme cases initiate controlled cell death (apoptosis). Mutations in p53 are frequently found in cancers, highlighting its importance in maintaining healthy cell populations. p53 is tightly controlled by diverse post-translational modifications, but the molecular details of how individual modification and combinations thereof contribute to p53 activity are poorly understood. This project uses synthetic protein chemistry (Müller lab) to investigate the biological outputs (Tavassoli lab) of specific p53 modifications.

Disciplines and Techniques
Project supervisor/s
Dr. Manuel Müller
Manuel is interested in the chemical biology approach to reveal when, where and how protein backbone modifications contribute to biological regulation.
King's College London
Professor Mahvash Tavassoli
Mahvash is interested in the study of cell cycle regulation and apoptosis machinery with the aim of developing molecular strategies to improve the detection and treatment of head and neck cancers.
King's College University
References
The multiple mechanisms that regulate p53 activity and cell fate
Hafner, A et al.
Nature Reviews Mol. Cell Biol. 20: 199.
2019
Semisynthesis of proteins by expressed protein ligation
Muir, T
Annual review of biochemistry 72: 249
2003
Histones: At the Crossroads of Peptide and Protein Chemistry
Müller, M and Muir, T.
Chemical Reviews115: 2296.
2015
p53 polymorphism influences response in cancer chemotherapy via modulation of p73-dependent apoptosis
Bergamaschi, D et al.
Cancer Cell. 3:387
2003
p53 is upregulated in Alzheimer’s disease and induces tau phosphorylation in HEK293a cells
Hooper, C et al
Neurosci. Lett. 418:34.
2007