Number of awards
Start date and duration
September 2020 for 3.5 years
Posttranslational modifications (PTMs) on histones play important roles in chromatin structure/function and transcriptional regulation, and abnormal PTMs are implicated in the onset and progression of many diseases.
Therapeutic strategies to target epigenetic proteins have shown promise, with a number of anti-cancer drugs currently in clinical use. Plant Homeodomain (PHD) fingers are small protein domains with zinc-binding motifs, often found as part of chromatin associated epigenetic proteins. Many PHD-fingers recognise and bind to histone PTMs, such as lysine methylation, thus are known as epigenetic “reader” domains. They can recruit protein / protein complexes or modulate the activity of their associated epigenetic enzymes - such as histone lysine demethylases and methyltransferases - and play critical roles in epigenetic regulation.
Mutations, amplifications and translocations of PHD-finger containing proteins have been linked to multiple diseases, and some PHD-fingers have been identified as potential cancer targets. There are currently no chemical probes against PHD-finger domains; chemical probes are urgently needed to further understand the biological roles of these important reader domain protein family.
The overall aim of this project is to develop high quality probes for the PHD-finger domains, in particular for PHD-fingers that can modulate the catalytic functions of associated histone demethylases or methyltransferases. This project will involve the biochemical and biophysical characterisation of PHD-fingers, the development of peptide-based probes, as well as target-specific cell-based assays, working at the interface of chemistry and biology.
The student will be well-supported in an integrated team and will work in a recently refurbished state-of-the-art chemical biology laboratory in the Bedson Building. Some aspects of the work will be carried out in collaboration with the epigenetics team in the Chemistry Department at University of Oxford.
Engineering and Physical Sciences Research Council (EPSRC)
Name of supervisor(s)
Professor Akane Kawamura (https://bit.ly/2U3oqvX
), Chair of Chemical Biology, Chemistry, School of Natural and Environmental Sciences
Successful candidates will have an excellent Master’s level degree in chemistry or chemical biology or a related subject. Outstanding Bachelor degrees plus relevant experience will also be considered.
The award is available to UK/EU applicants only. Depending on how you meet the EPSRC’s eligibility criteria, you may be entitled to a full or a partial award.
How to apply
You must apply through the University’s online postgraduate application system (https://bit.ly/3b9Tsbd
You will need to:
insert the programme code 8100F in the programme of study section
select ‘PhD in chemistry- Chemistry’ as the programme of study
insert the studentship code NES032 in the studentship/partnership reference field
attach a covering letter and CV. The covering letter must state the title of the studentship, quote reference code NES032 and state how your interests and experience relate to the project
attach degree transcripts and certificates and, if English is not your first language, a copy of your English language qualifications
Akane Kawamura. E-mail: [email protected]