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LRRK2 Direct-to-Biology Targeted Protein Degradation Assay Development and Screen: PIPS placement with Sygnature Discovery

Callum Ellis

Sygnature Discovery

The objective for Callum’s placement was to develop and test an assay that would be used to test 350 potential drugs. These drugs were targeted protein degraders using an approach called directed to biology in which the drugs are made in a crude reaction which can be used directly on cells, without the need for further purification. These drugs were designed to target a protein called LRRK2 which is implicated Parkinson’s Disease.

As part of his work Callum designed an assay using AlphaLISA and Toxilight technology, to optimize cell seeding density, feasibility of the technology, identify and test cost saving measures. Callum then used this assay to run a successful drug screen for 350 compounds to test their efficacy in degrading LRRK2, identifying over 40 compounds to take forward for further screening and optimization.

This placement allowed him to develop skills in assay design, development and optimization using novel technologies and innovative approaches to drug discovery and testing. He learned how to use various pieces of equipment including ECHO machines for nanolitre dispensing and used automation machines to expedite laboratory process and reduce potential variance and error. Callum used various pieces of analysis software, and built his understanding of structural drug design in the PROTAC/targeted protein degrader space, and delivered a presentation of his work to the bioscience and chemistry departments at the end of his placement.

This placement has allowed Callum to expand his network and understand more about CRO/drug discovery roles and solidified his desire to work in industry.