EPSRC DTP PhD project: A biomolecular toolkit for visualising and quantifying RNA-protein interactions in zebrafish

   Department of Life Sciences

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  Dr Nikolas Nikolaou  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

About the Project

The University of Bath is inviting applications for the following PhD project commencing on 30 September 2024 under the supervision of Dr Nikolas Nikolaou in the Department of Life Sciences with co-supervison from Prof Sofia Pascu (Chemistry) and Dr Ian Eggleston (Life Sciences).

Eligible applicants will be considered for a fully-funded studentship – for more information, see the Funding Notes section below.

Overview of the Research:

Key references:

  1. Nikolaou, N., Gordon, P.M., Hamid, F., Taylor, R., Lloyd-Jones, J., Makeyev, E.V., Houart, C. (2022) Cytoplasmic pool of U1 spliceosome protein SNRNP70 shapes the axonal transcriptome and regulates motor connectivity. Current Biology https://doi.org/10.1016/j.cub.2022.10.048 
  2. Exner, R. M., Cortezon-Tamarit, F., Ge, H., Pourzand, C., Pascu, S. (2022). Unravelling the Chemistry of meso-Cl Tricarbocyanine Dyes in Conjugation Reactions for the Creation of Peptide Bonds. ACS Bio & Med Chem Au. https://doi.org/10.1021/acsbiomedchemau.2c00053 

This is a project at the interface of chemical biology and biological chemistry with a focus in the biophysical investigation of RNA-protein complexes using new synthetic molecular imaging tools. It is of relevance to the Healthcare Technologies remit of the EPSRC and builds on our collaboration spanning biophysical research in model organisms (Nikolaou), peptide chemistry (Eggleston), and bioinorganic synthetic chemistry for imaging chemistry (Pascu). RNA-protein interactions play an integral part in several important biological functions that include: (i) transcription, (ii) translation, and (iii) regulation of gene expression, and their role is particularly important in neurons. This project will help unravel the mechanisms by which the activities of axonal RNA-binding proteins (RBPs) regulate the wiring of brain cells. Our recent work on the cytoplasmic function of SNRNP70 in motor neurons (Nikolaou et al., 2022) contributed to the recent state-of-the-art showing that neuronal connectivity depends on the activities of axonal RBPs to regulate mRNA localisation and processing. Many RBPs have been implicated to neurological diseases, indicating the importance of axonal RNA-protein interactions in neurons. The aim of this project is to design and produce synthetic probes for monitoring RNA-protein dynamics in neurons using the translucency of zebrafish embryos/larvae, where all components of a neural circuit are intact.

We will achieve the aim of the project by following these approaches:

(1)   generate short synthetic peptides fused to fluorophores (Exner et al., 2022), which can recognise RBPs of interest and record their localisation over time.

(2)   generate fluorescent protein-nucleic acids to report the localisation of known RNAs interacting with candidate RBPs of interest in the nucleus and axons.

(3)   confirm and validate RNA-protein interactions and use Förster-resonance-energy-transfer (FRET) coupled with fluorescence-lifetime-imaging-microscopy (FLIM) to visualise such interactions in living cells.

This should be a straight-forward alternative to the current methods, requiring the manipulation of cells to overexpress either the protein of interest fused to a fluorescent protein or fluorescently tagged transcripts. These methods are limited in that the overexpression of proteins and mRNA transcripts in cells could lead to unwanted effects. This project will suit someone who is keen on working at the interface between biology, biological chemistry, and chemical biology, is enthusiastic about studying RNA-protein complexes in cells and organisms and wants to determine new synthetic approaches to imaging RNA-protein localisation and function.

Project keywords: biophysical characterisation in model organisms, such as zebrafish; RNA binding proteins (RBP); RNA-protein interactions in living cells; functional near-infrared (NIR) emitting tags and synthetic peptides; peptide synthesis; fluorescent peptide nucleic acids.

Candidate Requirements:

Applicants should hold, or expect to receive, a First Class or good Upper Second Class UK Honours degree (or the equivalent) in Biology, Biochemistry, Chemistry or Natural Sciences. A master’s level qualification would also be advantageous but is not essential.

Non-UK applicants must meet our English language entry requirement.

Enquiries and Applications:

Applicants are encouraged to contact Dr Nikolas Nikolaou on email address [Email Address Removed] before applying to find out more about the project and to discuss their suitability for the role.

Formal applications should be made via the University of Bath’s online application form for a PhD in Biochemistry

In the ‘Funding your studies’ section of the application form, please select ‘EPSRC DTP’ from the first drop-down menu. In the ‘Your PhD project’ section, please quote the project title and lead supervisor’s name in the appropriate fields. Failure to complete these steps will cause a delay in processing your application and may cause you to miss the deadline.

More information about applying for a PhD at Bath may be found on our website.

Equality, Diversity and Inclusion:

We value a diverse research environment and aim to be an inclusive university, where difference is celebrated and respected. We welcome and encourage applications from under-represented groups.

If you have circumstances that you feel we should be aware of that have affected your educational attainment, then please feel free to tell us about it in your application form. The best way to do this is a short paragraph at the end of your personal statement.

Biological Sciences (4) Chemistry (6)

Funding Notes

Candidates applying for this project may be considered for a 3.5-year Engineering and Physical Sciences Research Council (EPSRC DTP) studentship. Funding covers tuition fees, a stipend (£18,622 per annum, 2023/24 rate) and research/training expenses (£1,000 per annum). EPSRC DTP studentships are open to both Home and International students; however, in line with guidance from UK Research and Innovation (UKRI), the number of awards available to International candidates will be limited to 30% of the total.

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