About the project
This project targets mRNA IRES structures of oncogenes using modified oligonucleotides to avoid broad translational inhibition. We will optimise ON modifications, transfection, and efficacy in organoids, focusing on lung and blood cancers. The goal is an adaptable, highly selective technology for precise regulation of multiple oncoproteins.
Translation of cellular mRNAs via initiation at internal ribosome entry sites (IRESs) has received increased attention in recent years due to its emerging significance for many physiological and pathological stress conditions in eukaryotic cells. This cap-independent expression mechanism seems to be a vital survival mechanism in many cancers where the normal translation pathway is compromised. Many oncogenes have been show to contain IRES type RNA sequences, which offer a novel target for personalised cancer therapy.
As part of the Horizon Europe funded project ON-TRACT, the aim of this project is to build on our development of modified ONs for the highly selective targeting of mRNA IRES structures of several oncogenes, thereby avoiding potential confounding effects of broader translational inhibition. We will investigate in the application of different ON modifications, in targeted transfection, evaluation of efficacy in gene regulation (up or down) in organoids, and optimisation of the system towards lung and blood cancer. This will allow us to test an adaptable technology for selective targeting of multiple oncoproteins and to rigorously assess the IRES specificity of our targeting ONs.
You'll receive training in all scientific aspects around DNA chemistry, organic synthesis, purification and analysis. As this project is part of a European Doctoral Network, there are several network wide training weeks at different European locations planned, where both scientific as well as transferable skills training will be delivered.
The School of Chemistry and Chemical Engineering is committed to promoting equality, diversity inclusivity as demonstrated by our Athena SWAN award. We welcome all applicants regardless of their gender, ethnicity, disability, sexual orientation or age, and will give full consideration to applicants seeking flexible working patterns and those who have taken a career break. The University has a generous maternity policy, onsite childcare facilities, and offers a range of benefits to help ensure employees’ well-being and work-life balance. The University of Southampton is committed to sustainability and has been awarded the Platinum EcoAward.
In addition to the University of Southampton supervisor, this project has the following external supervisors:
- Professor Florian Hollfelder (University of Cambridge)
- Dr Rosanne Veerman (Strike Pharma)
