Engineering functional chromatin elements for high-throughput screening

This is a UK Centre for Mammalian Synthetic Biology Studentship.

Interested individuals must follow Steps 1, 2 and 3 at this link on how to apply:

http://www.ed.ac.uk/biology/prospective-students/postgraduate/pgr/how-to-apply

Supervisors: Dr Abdenour Soufi ([Email Address Removed]) and Prof Susan Rosser ([Email Address Removed])

The association of DNA with histone proteins forms repeating nucleosome units within the chromatin. Specific histone tail modifications such as methylation and acetylation serve as epigenetic marks of promoters and enhancers that control specific gene expression. Chromatin regulatory proteins have emerged as promising targets for drug development – particularly in oncology. For example, BET inhibitors can reverse the cancer phenotype of multiple haematological cancers 1, 2. Many TFs also represent potential therapeutic targets, but despite their central roles in cell identity and tumorigenesis they have been largely regarded as ‘undruggable, because they operate through protein-protein and protein-DNA interactions rather than enzymatic activities. Development of new screening platforms that can facilitate identification of small molecules inhibitors of either chromatin modifiers or TFs would therefore have great value.

We previously showed that reconstituting cell-type specific enhancers into nucleosomes can recapitulate prominent native chromatin features in vitro 3. The goal of this project is to develop a novel drug discovery platform, based on the binding of TFs to enhancer elements within reconstituted chromatin in vitro that will enable screening for modulators of specific TF in specific cellular contexts. The PhD student candidate will be trained on the state of the art synthetic biology techniques. The student will be actively involved in developing bioinformatics tools to integrate and analyse large data sets generated from a variety of experimental approaches. In addition, the student will part of two research groups covering diverse disciplines such as Synthetic Biology, Epigenetics, Stem Cells and regenerative medicine.

Supervisors: Dr Abdenour Soufi and Prof Susan Rosser

http://www.crm.ed.ac.uk/research/group/chromatin-structure-and-cellular-identity

http://rosser.bio.ed.ac.uk

The PhD student will become part of a cohort of graduates students linked to the research of the new UK Centre for Mammalian Synthetic Biology (the ‘Centre’), based at the University of Edinburgh. Through support from the Research Council’s Synthetic Biology for Growth programme and of the BBSRC, EPSRC and MRC, the University has been awarded ~ £18M in funding to establish a national facility for DNA synthesis (the Edinburgh Genome Foundry) and one of six UK Centres of Excellence in Synthetic Biology. Edinburgh’s Centre embeds colleagues from the College of Medicine and Veterinary Medicine, in particular from the Scottish Centre for Regenerative Medicine. More information about our Centre can be found at http://www.synbio.ed.ac.uk and follow us on Twitter @SynthSysEd.

This is an exciting opportunity to be at the cutting edge of this fast moving area of science and technology in world-leading research institutes. We are looking for highly motivated graduates who are enthusiastic about the potential of this new area of science and keen to work across disciplines.