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Research overview

Dr Paul Clarke, RNA Biology and Molecular Therapeutics

The RNA Biology and Molecular Therapeutics Team works within the multidisciplinary environment of the Division of Cancer Therapeutics to identify novel targets for drug discovery and to support the discovery of new small-molecule therapeutics to inhibit these targets.

Specifically, we aim to carry out cutting-edge research into the roles of RNA binding proteins and their complexes in cancer and to target the addiction or dependency of cancer cells on these proteins or complexes through the discovery of innovative and effective drugs.

RNA has a key role in enabling the flow of genetic information from DNA to proteins. It has become increasingly clear that mutation altered expression or activity of the cellular machinery required for processing, modification, translation, and turnover of RNAs have a critical role in the etiology of cancer.

We currently support validation and mechanism of action studies for commercially partnered drug discovery projects targeting RNA binding proteins that regulate splicing and protein synthesis initiation.

We employ a multi-disciplinary approach, integrating molecular and cellular biology with global profiling to determine the molecular impact of target modulation by genetic methods or small molecules on RNA binding, pre-mRNA processing and ribosome binding to mRNA. We use PROTAC-based strategies for validation of targets and their binding pockets, using bi-functional small molecules to induce target protein degradation.

We plan to build on these activities and introduce RNA oligo-PROTAC target validation methods and to expand our drug discovery activities to a wider class of RNA binding proteins that modulate RNA structure and processing.

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