PhD Studentship: How do non-coding enhancer RNAs regulate epigenetic-enzymes and chromatin in healt

Only a small amount of the genome contains genes that code for proteins. In fact, much of the genome is transcribed into RNA, but the importance of these non-coding RNAs is only just becoming clear. In the Bose lab, we study one type, called enhancer RNAs (eRNAs), that come from regulatory DNA sequences called enhancers. All the cell-types in multicellular organisms rely on enhancers to control the gene-expression patterns that maintain a cells’ identity. Different enhancers have different abilities to promote gene expression, and their mutation and aberrant usage is prevalent in and causative for many human diseases, including cancer. However, the mechanisms underlying these disease outcomes remain poorly understood. Our work has shown that eRNAs can regulate gene expression by interacting with the epigenetic-enzymes that control the structure of chromatin. We want to understand the mechanisms that eRNAs use to generate different enhancer activities, and to understand how de-regulation of these activities leads to disease and cancer.

The successful PhD candidate will join our newly established, multidisciplinary research group as the part of the Sheffield Institute for Nucleic Acids (SInFoNiA) and Department of Molecular Biology and Biotechnology at the University of Sheffield. The project will address exciting and relevant questions in this fast-moving field, providing a deep understanding of how chromatin can regulate gene expression and the importance of non-coding RNAs in this process. The PhD will offer a broad, interdisciplinary training in modern functional-genomics, RNA biology and biochemistry, with opportunities to develop structural cryo-EM and biophysical aspects of the project. The candidate will be part of an exciting and dynamic graduate research program within SInFoNiA, and will also enjoy extensive interactions and support from biologists, biophysicists and structural biologists in the Department and within the Imagine: Imaging life project.

The successful PhD candidate will have demonstrated enthusiasm, understanding and motivation for studying aspects of gene-regulation, RNA and chromatin biology. You should have, or expect to achieve, a first or upper second class UK honours degree or equivalent. This should be in a relevant area (For example: Molecular Biology, Biochemistry, Biophysics, Genetics).

For informal enquiries and further information about the project, please contact Dr Daniel Bose (d.bose@sheffield.ac.uk).

Funding Notes

• Full tuition fees (UK and EU).
• Annual, tax-free maintenance stipend at the standard RCUK rate (2016/17 is £14,296).
• Research Training Support Grant to cover international travel, secondments and exchanges.
• These scholarships fund up to 3.5 years full-time study, subject to satisfactory progress.

Eligibility:

• You should have, or expect to achieve, a first or upper second class UK honours degree or equivalent. This should be in a relevant area (e.g. Molecular Biology, Biochemistry, Biophysics, Genetics).

Scholarships are awarded on a competitive basis - applications are assessed on the basis of academic success and qualifications,
experience, research background
 

References

Bose, D.A., Donahue, G., Reinberg, D., Shiekhattar, R., Bonasio, R., and Berger, S.L. (2017). RNA Binding to CBP Stimulates
Histone Acetylation and Transcription. Cell 168, 135–149.e22.

Adelman, K., and Egan, E. (2017). Non-coding RNA: More uses for genomic junk. Nature 543, 183–185.