07.12.20

High Throughput Discovery Update

The Franklin is pleased to announce that the High-Throughput Discovery Facility is progressing to the next stage of its establishment. The facility is currently being set up at the University of Leeds and will move to the Franklin Hub next year. This collaboration represents a strong partnership between the Franklin and Leeds’s world-leading Astbury Centre, which will continue grow over the coming years.

Chemistry is key for drug discovery and the facility in coming years will enable the rapid synthesis of novel molecules (small and large), so that we can better understand and modulate novel targets for treating disease. The lab aims to expand the reaction toolkit used in molecular discovery, enabling new regions of therapeutically relevant chemical space to be explored. It has been argued that the current reaction toolkit that underpins many small-molecule drug-discovery workflows, is dominated by around ten reaction classes, that have largely remained unchanged for 30 years. This has been considered one source of the high attrition and stagnation in drug discovery. The High-Throughput Discovery Facility hopes to disrupt this and lead the way in producing new starting points for drug discovery by exploring the functional consequences of parallel manipulation in relevant biological contexts..

Professor Adam Nelson, lead scientist from the University of Leeds, explains: “Currently, drug discovery is a rather conservative process – using a small number of building block types and a limited suite of reactions means we are only exploring a very fraction of drug-relevant chemical space.”

“You can think of chemical space a bit like geographic space – it’s like exploring London and ignoring all the other cities, towns, and countryside.  This might be good for finding an interesting museum, but less good if you want to find the highest point in the UK!”

The High-throughput Discovery facility has been designed to enable greater integration of the individual stages within discovery workflows, with high and matched throughput throughout. This will allow us to exploit, for example, high-throughput crystallographic screening of “poised” fragments that align with less conservative chemistry, harness a reaction toolkit that enables direct fragment elaboration and permit functional evaluation of products within crude reaction mixtures.

The lab aims 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 current reaction toolkit. This will require the integration of algorithmic methods, synthetic chemical methodology, chemical engineering, structural biology, chemical 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 to enable precise biological modulation.

Over the next few months, we will be getting the various pieces of instrumentation for the lab delivered and installed at the University of Leeds and at the new Harwell Building. A burgeoning team high-throughput molecular discovery scientists from collaborating groups will begin to develop and establish methods that will enable new bioactive molecules to be discovered. The facility will fully relocate to the Hub next year

Professor Ben Davis, our Next-Generation Chemistry lead, said: “The High-Throughput Discovery Facility will provide globally significant advances in molecular discovery over the coming years, by exploring new realms of high-throughput methods that have been rarely tested, and is a key part bringing to life the Franklin’s vision for revolutionising how we understand biology, develop biotechnology and treat disease.”

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