Unravelling the enigma of why humans require seven distinct histone deacetylase complexes – implications for therapeutic intervention
There are seven families of class I histone deacetylase complexes that play a role in many cellular processes, such as cancer, cell cycle progression and DNA repair. Investigating how these HDAC complexes act to control gene expression and their interactions with other proteins should lead to an understanding of their influence in the cell.
HDAC inhibitors are currently used to treat some cancers, epilepsy and schizophrenia. They are also promising therapeutics for a number of other diseases such as spinal muscular atrophy, Friedrich’s ataxia, Alzheimer’s disease, HIV infection and heart disease. An understanding of the structure and function of the different histone deacetylase complexes will allow inhibitors to be designed against specific complexes to reduce side effects (for a review Millard et al. 2017).
We hope to unravel the contributions of each HDAC complex to gene expression in the cell using a range of techniques such as: Chromatin immunoprecipitation using anti-FLAG antibodies to enable comparison between genome locations of the seven complexes; Protac-mediated destruction of the complexes to identify changes in gene expression and histone acetylation using RNAseq and ChIP; Mass spectrometric analysis of the proteomes associated with each of the complexes using the RIME approach.
You must hold (or be about to obtain) a First or an Upper Second Class UK undergraduate degree or an equivalent degree from a recognised EU institution, in an area relevant to the projects you are applying for.
Qualifications (or a combination of qualifications and experience) which demonstrate equivalent ability and attainment will also be considered.
For example, a less than sufficient first degree may be enhanced to meet the requirements by the acquisition of a Distinction at Masters level or significant research experience gained from employment).
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The Studentship provides 3.5 years of Stipend at UKRI rates and Tuition fees at UK/EU rates.