High Throughput Discovery Laboratory

The High Throughput Discovery Lab aims to integrate diversity of synthesis with contextual functional effects. Chemistry is a cornerstone of molecular discovery in Biology and the innovative High-throughput Discovery facility, started by Adam Nelson will be integrated with other sub-theme projects to enable the rapid synthesis and, critically, assessment of novel compounds (large and small), so that we can understand, reach and act on disease targets.

The project aims to iteratively expand the reaction toolkit used in molecular manipulation to discovery, enabling new regions of biologically relevant chemical space to be explored. The current reaction toolkit, that underpins traditional drug discovery workflows, has to date been dominated by a small number (<10) of reaction classes that have remained largely unchanged for 30 years. It has been argued that this has contributed to attrition and stagnation in drug discovery. The High-Throughput Discovery facility hopes to disrupt this by using new methods and direct functional assessment in context to lead the way in the production of new starting points for drug discovery with varying modalities.

The facility has been designed to deliver a step-change in molecular discovery: both in increased efficiency, through faster and parallel design-make-test cycles, and effectiveness, by harnessing chemistry that is currently outside the discovery toolkit. This will require the integration of algorithmic methods, synthetic methodology, reaction and chemical engineering, structural biology and biophysics. By embedding high-throughput closed-loop methods in direct functional biological contexts in vitro, in crystallo, and in cellulo, we aim to guide and select data that will refine chemical structures towards precise biological modulation

Project team members:

• Project leader:  Adam Nelson, University of Leeds
• Stefan Lohmann
• Sofia Piticari
• Niamh Morris
• Liang Wu
• Ben Davis

Project Partners:

Astbury Centre

University of Oxford

Diamond Light Source

Evotec

University of Leeds

Max Planck Institute of Molecular Physiology

Funded by:

IMI2 EUbOPEN Initiative

Evotec