Fully funded industrial collaboration PhD understanding nucleolus-associated toxicity of antisense oligonucleotides at King’s College London, UK (Worldwide students)
Posted on December 2, 2024
We invite applications from passionate and driven candidates for a unique interdisciplinary PhD position to explore the nucleolus-associated toxicity mechanisms of antisense oligonucleotides (ASOs), an emerging class of gene-specific therapeutics targeting RNA. The successful candidate will develop novel insights into how toxic ASOs interact with subcellular compartments, particularly the nucleolus, influencing ribosomal biogenesis and cell survival.
Application Deadline:
Applications must be complete, including both references, by 11th December 2024
Supervisors:
1. Eugene Makeyev ([email protected])
2. Tracy Nissan ([email protected])
About the project:
Therapeutic ASOs have shown remarkable promise, yet the underlying toxicity mechanisms limit their broader application. This London Interdisciplinary Biosciences Consortium iCASE project will address this challenge by:
1. Investigating the impact of toxic ASOs on nucleolar structure in human cells.
2. Identifying ASO-induced changes in the nucleolar interactome using advanced proximity labelling tools.
3. Examining how ASO-driven nucleolar disruptions influence ribosome production and cell viability.
Working at King’s College London, with a 3-month placement at AstraZeneca’s Cambridge Biomedical Campus, the candidate will receive hands-on training in molecular biology, imaging, proteomics, and proximity labelling, gaining a well-rounded skillset in both academic and industrial settings.
What we offer:
1. A collaborative environment connecting top academic and industrial scientists.
2. Training in advanced imaging, proteomics, and cellular biology techniques.
3. The chance to contribute to BBSRC-priority research with high-impact implications for ASO therapeutics.
Candidate requirements:
Successful applicants will have a BSc (and preferably an MSc) in Life Sciences or related fields, with substantial research experience in molecular biology, biochemistry, or cell biology. A keen interest in RNA biology, subcellular dynamics, and molecular therapies is essential, and experience with imaging, proteomics, or bioinformatics is advantageous.
References:
Crooke, S.T., Baker, B.F., Crooke, R.M., Liang, X.-H. (2021) Antisense technology: an overview and prospectus. Nat Rev Drug Discov 20, 427-453. https://doi.org/10.1038/s41573-021-00162-z
Yap, K., Chung, T.H. and Makeyev, E.V. (2022) Hybridization-proximity labeling reveals spatially ordered interactions of nuclear RNA compartments. Mol Cell 82, 463-478 e411. https://doi.org/10.1016/j.molcel.2021.https://doi.org/10.009
Yap, K., Mukhina, S., Zhang, G., Tan, J.S.C., Ong, H.S. and Makeyev, E.V. (2018) A Short Tandem Repeat-Enriched RNA Assembles a Nuclear Compartment to Control Alternative Splicing and Promote Cell Survival. Mol Cell 72, 525-540 e513. https://doi.org/10.1016/j.molcel.2018.08.041
Funding Notes:
Fully funded place including home (UK) tuition fees and a tax-free stipend in the region of £21,237. Additional funding to cover full overseas fees is available for a maximum of 7 studentships.
Enquiries email name and address:
[email protected]
Application Web Page:
https://www.lido-dtp.ac.uk/apply
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