About the Project
ELAV/Hu proteins comprise a family of highly conserved RNA binding proteins predominantly expressed in neurons where they have roles in regulating synaptic connectivity important for learning and memory. Aberrant regulation of ELAV/Hu proteins has been linked to neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease. In addition, a number of cancers aberrantly express ELAV/Hu proteins including glioblastoma, pancreatic, colorectal and lung cancers, but the molecular mechanisms…
leading to these diseases are not understood.
RNA binding proteins bind short motifs. These motifs, however, are degenerate and highly redundant in the genome. How they exactly generate specificity to filter the correct targets in such a degenerate sequence space, is currently not clear, but likely includes combinatorial interactions of RNA binding proteins.
We have discovered that ELAV/Hu proteins can multimerize. Now we will employ cryoEM to build a structure for multimeric ELAV complexes bound to RNA and test the role of multimerization mediated RNA recognition in neurodegeneration and cancer using a Drosophila genetic model.
Eligibility
Candidates are expected to hold (or be about to obtain) a minimum upper second class honours degree (or equivalent) in Molecular Genetics, Structural Biology or a related area. Candidates with experience in Structural Biology, Drosophila genetics or with an interest in mRNA processing are encouraged to apply.
Before you Apply
Applicants must make direct contact with preferred supervisors before applying. It is your responsibility to make arrangements to meet with potential supervisors, prior to submitting a formal online application.
How to Apply
To be considered for this project you MUST submit a formal online application form – on the application form select PhD Structural Biology. Full details on how to apply can be found on the Website: How to apply for postgraduate research at The University of Manchester
If you have any queries regarding making an application please contact our admissions team FBMH.doctoralacademy.admissions@manchester.ac.uk
Equality, Diversity and Inclusion
Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website: Equality, diversity and inclusion (EDI | Postgraduate Research | Biology, Medicine and Health | University of Manchester
Funding Notes
Applications are invited from self-funded students. This project has a Band 1 (low) fee. Details of our different fee bands can be found on our website View Website
References
Dix, T., McQuarrie, D.W.J., Brauer, U., Tian Y.W., Haussmann, I. U., Li, M., Futterer, K. and Soller, M. (2026) Multimerization of ELAV in Drosophila is essential for directing neuronal alternative splicing and polyadenylation programs. Genes & Development, in press.
https://doi.org/10.1101/gad.353688.126
McQuarrie, D. and Soller, M. (2024). Phylogenomic instructed target analysis reveals ELAV complex binding to multiple optimally spaced U-rich motifs. Nucleic Acid Research 52: 12712-26.
Ustaoglu, P., Gill, J.K., Doubovetzky, N., Haussmann, I.U., Dix, T.C., Arnold, R., Devaud J.M. and Soller, M. (2021) Dynamically expressed single ELAV/Hu orthologue elavl2 of bees is required for learning and memory. Communications Biology, 4: 1234.
Zaharieva, E., Haussmann, I. U., Brauer, U. and Soller, M. (2015) Concentration and localization of co-expressed ELAV/Hu family proteins control specificity of mRNA processing. Mol. Cell. Biol. 35: 3104-3115.
Soller, M. and White, K. (2005). ELAV multimerizes on conserved AU4-6 motifs important for ewg splicing regulation. Mol. Cell. Biol. 25: 7580-7591.