This opportunity will remain open until the position has been filled.
Post-translational modifications (PTMs) of histones are known to direct chromatin structure and thus gene transcription. This so called “histone code” hypothesises that the combination of PTMs on different histones are a driving force that regulate DNA packing and thus the ability of different genes to be accessible for transcription or ‘silenced’. Work from our groups and others have also defined specific histone codes as markers of cancer and other diseases.
Using novel technology recently developed in our lab for the cell-wide identification of sites of non-canonical phosphorylation (NCP) on e.g. histidine, lysine, arginine using mass spectrometry, we have identified NCP sites on numerous histone proteins and enzymes that regulate histone PTM status. These findings raise the possibility that the histone code, as we understand it, may very well be incomplete. This project aims to re-define the histone code and its regulation, using methods that are compatible with retaining sites of non-canonical phosphorylation. Furthermore, we will explore the relationship between this re-defined histone code and chromatin structure, and thus the implications for transcriptional regulation.
This project is a collaboration between active research groups in Liverpool and Newcastle.
· Claire Eyers (Director, Centre for Proteome Research, https://www.liverpool.ac.uk/cpr/; Twitter: @ClaireEEyers) – https://www.liverpool.ac.uk/integrative-biology/staff/claire-eyers/
· Jonathan Higgins https://www.ncl.ac.uk/medical-sciences/people/profile/jonathanhiggins-1.html
· Andy Jones (Director, Computational Biology Facility, https://www.liverpool.ac.uk/computational-biology-facility/; Twitter: @andy___jones) – https://www.liverpool.ac.uk/integrative-biology/staff/andrew-jones/
By combining our unique areas of expertise in MS-based PTM discovery and analysis, and chromosome biology, we are in an ideal position to undertake these studies. Our main objectives are:
1. Characterise PTMs (including NCP) on chromatin-associated proteins, correlating with respect to chromatic states (e.g. heterochromatin, euchromatin, mitotic chromatin). We will redefine the PTM complement (the histone code) and explore the interplay between different PTMs (either on the same site, different sites) as a function of chromatin structure.
2. Using bioinformatic and computational approaches, predict the roles of identified NCPs on histone modifying enzymes, validating function using a range of biochemical and cell biology assays to explore the effect of NCP on enzymatic activity and complex formation.
You will receive broad training in phosphorylation-mediated signalling and chromosome biology. Specific training will be provided in cutting edge proteomics techniques and the associated computational analysis tools for protein/proteomics data and pathway interrogation, making you highly employable across the field of biological sciences.
For any enquiries please contact Professor Claire Eyers: [Email Address Removed]
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