Fully funded PhD studentship in our lab!

Written By SWM

We are offering a fully funded PhD project focused on engineering fluorescently tagged prions in human cells via genetic code expansion and bio-orthogonal labeling. The successful candidate will employ cutting-edge imaging techniques, such as single-molecule localisation microscopy (SMLM) and cryo-correlative light and electron microscopy (cryo-CLEM), to study prion dynamics and structures in situ at high resolution.

Application Deadline: 18 May 2025

〰️

Application Deadline: 18 May 2025 〰️

Engineering human cells to propagate fluorescent prions for live monitoring of prion infection dynamics and in situ prion structure determination

Duration: Fully funded 3-year studentship

Start date: October 2025

Hosted by: Dr Szymon W. Manka, Senior Lecturer in Structural Biology, Section of Structural and Synthetic Biology, Department of Infectious Disease, Imperial College London, South Kensington Campus

Overview: The molecular mechanisms underlying prion protein (PrPC) conversion into infectious prion assemblies are poorly understood due to the lack of tools for real-time tracking of prion propagation at sufficient resolution. To advance our understanding of pathogenic pathways related to human prion diseases at the nanoscale level, it is essential to develop a fluorescent tagging method that can label prions under live, native conditions. This approach will help capture intermediate states and transient interactions with cellular factors that may be relevant to human prion diseases.

The project will utilise genetic code expansion (GCE) technology to site-specifically incorporate a fluorescently-taggable non-canonical amino acid (ncAA) into ovine (sheep) PrP expressed in human nerve-like cells devoid of endogenous (human) PrP for safety reasons. Previous work in the Manka lab involved incorporating an ncAA-compatible with tetrazine-based click chemistry into PrPC in mouse neuroblastoma N2a cells and primary mouse cortico-hippocampal neurons, resulting in a fluorescently labelled PrPC with only a single amino acid modification that supported mouse prion propagation (manuscript in preparation). Building on this success, we aim to implement the same technology in human cell lines that can be differentiated into functional neurons, for increased relevance to human prion diseases. By fluorescently co-tagging potential prion interaction partners identified through genome-wide CRISPR screens conducted in the Aguzzi lab we hope to pinpoint and structurally characterise nascent prions together with their disease-relevant interactors in the native context using single-molecule localisation microscopy (SMLM) and cryo-correlative light and electron microscopy (cryo-CLEM).

How to apply: Please send your CV, a cover letter and details of at least two referees to smanka@ic.ac.uk by 18 May 2025, inclusive.

In the cover letter, please explain:

  • what motivates you to do scientific research and pursue a PhD,

  • why you are interested in this project and our lab,

  • your qualities, skills and any experience that has helped prepare you to start a PhD.

Student eligibility: Applicants must have or expect to gain the equivalent of a UK Upper Second class or higher undergraduate degree in a relevant subject, including (but not limited to) molecular biology or biochemistry. A Masters degree is desirable but not essential. Applicants are also required to meet Imperial College’s English language requirements. Please, see the following link: https://www.imperial.ac.uk/study/ug/apply/requirements/english/.

For further details please contact Dr Manka at smanka@ic.ac.uk

SWM
Next

Perspective on what the novel CWD prion structure means for the prion field