Research Associate - Oligonucleotide Immune Therapies

Research Associate - Oligonucleotide Immune Therapies
University of Cambridge
Cambridge, United Kingdom
GBP 33,002 - GBP 46,049 per year
Advanced therapies based on modified mRNA and antisense oligonucleotides are transforming the treatment of cancer, neurodegenerative disease and infection, but their full potential will only be realised if they can be designed to be both powerful and safe. This post will develop new experimental systems to understand how these therapeutics activate innate immune pathways, and to use that knowledge to make them "safer by design". The successful candidate will work at the interface of RNA biology, immunology and toxicology, building models that identify when immune activation is harmful, when it can be harnessed for therapeutic benefit, and how these responses can be engineered in the next generation of nucleic acid medicines.
A Research Associate is required to establish new experimental models to understand how nucleic acid therapeutics, including antisense oligonucleotides and modified mRNA therapeutics, activate innate immune signalling pathways in complex models. The post will sit within a new collaborative programme between the laboratories of James Thaventhiran, Marion MacFarlane and Anne Willis at the MRC Toxicology Unit and AstraZeneca R&D, and foster collaboration with Menna Clatworthy, Fotios Sampaziotis and Eoin McKinney at CITIID, University of Cambridge. They will work within an MRC-funded Prosperity Partnership with AstraZeneca, improving cell models, to enable high-throughput quantification of the contribution of immune cells and immune signalling to the oligonucleotide tissue response.
The central aim of the post is to develop robust, mechanistically informative systems that can detect and dissect immune activation by therapeutic nucleic acids. The post-holder will use these models to identify the molecular features and cellular pathways that determine inflammatory, toxic or therapeutically useful responses. They will then test strategies to modify these responses, either to reduce unwanted toxicity or to enhance therapeutic efficacy. The project will provide an opportunity to work across cellular immunology, RNA biology, translational toxicology and advanced pre-clinical models. Depending on the direction of the work, this includes reporter cell-model generation, CRISPR or perturbation-based approaches, transcriptomic and proteomic analysis, modified mRNA and ASO delivery systems, murine models, and ex vivo perfused human organ systems.
The post is intended to support the development of an outstanding early-career scientist towards research independence. The successful candidate will be encouraged to generate a coherent body of preliminary data over the first two years in post, with the aim of developing a competitive postdoctoral fellowship application to schemes such as those offered by Wellcome, MRC, Cancer Research UK or equivalent funders.
The post would suit a highly motivated scientist with a strong background in innate immunology, advanced organoid/3D culture models, RNA biology, molecular cell biology, medicines safety, nucleic acid therapeutics or related disciplines. We are particularly interested in candidates who can combine rigorous experimental biology with the intellectual drive to shape a new area of translational research. Applicants must hold, or be close to completing, a PhD in a relevant discipline.
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Deadline 13 October
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University of Cambridge