Project 1: CRISPR Library Screening to Identify Endogenous HEK293 Genes Impacting AAV Production
Supervisors: Prof. Niall Barron and Assoc. Prof. Colin Clarke
CRISPR library screening has proven powerful for identifying genetic determinants of cellular phenotypes, including cancer mechanisms, bioreactor behaviour, and viral restriction. This unbiased approach allows genome wide interrogation through gene knockout or activation. This project will apply CRISPR screening to a suspension adapted HEK293 cell line to identify genes that enhance or inhibit AAV production. A human CRISPR guide RNA library will generate a knock out population. Cells producing high and low AAV levels will be isolated, sequenced, and analysed to identify enriched guide RNAs and target genes. Key genes will be validated via targeted knockouts and assessed for AAV yield following triple transfection.
How to apply:
Project 1 applicants should email: a cover letter (including your motivation statement outlining why you wish to do a PhD and why you are suited to this project), a CV, and contact details for your academic referees to [email protected]
Informal enquiries to [email protected]. Funding includes a €25,000 annual stipend plus fees for four years.
Project 2: Improving rAAV Safety through Glycoengineering
Supervisor: Dr Ioscani Jiménez del Val
Recombinant AAVs are the leading gene therapy vectors, with eight approved therapies and more than 250 in clinical trials. However, doses required for efficacy can trigger immune responses that reduce effectiveness and, in rare cases, cause severe adverse outcomes. rAAV capsids contain complex glycans, with high‑mannose structures known to stimulate immune recognition. Recent studies show most rAAV glycans are high‑mannose.
This project aims to convert pathogenic glycans into non‑immunogenic structures. Initial work will focus on in vitro enzymatic glycan remodelling. Following demonstration of immunological benefit, HEK293 cells will be genetically engineered to directly produce glycoengineered rAAV. The project combines enzyme catalysis, molecular biology, cell culture, assay development, and data analytics.
How to apply:
Applicants should submit a cover letter, CV, and motivation letter via https://forms.gle/ZTjUWotqvodkr9nK7 by 31/05/2026. Informal enquiries to [email protected]. Funding includes a €25,000 annual stipend plus fees for four years.
Project 3: Process Analytical Technology Applications for Monitoring AAV Production
Supervisor: Dr Jonathan Bones
This project focuses on developing process analytical technologies (PAT) for monitoring AAV production during cell culture. While PAT is widely used for chemical synthesis and protein biologics, its use for AAV is limited by viral complexity and low expression. The project will explore inline, online, and at‑line analytical methods supported by automated sampling in small‑scale bioreactors. Students will operate bioreactors, deploy spectroscopic and integrated analytical tools, generate large datasets, and apply multivariate and statistical approaches to enable advanced process control.
How to apply:
Applicants should email a covering letter, motivation statement (outlining why you would like to do a PhD), CV, and referee details to [email protected]. Informal enquiries to [email protected]. Funding includes a €25,000 annual stipend plus fees for four years.
