Researchers at the Francis Crick Institute and GSK will extend their ongoing collaboration to advance the discovery of new drug targets in a £11.5million effort, thanks to a ‘Prosperity Partnership’ grant from the Engineering and Physical Sciences Research Council (EPSRC) and matching funds from GSK announced today (Friday).
Together the teams will develop and industrialise emerging technology in chemical biology based upon ‘reactive fragment’ screening.
Recent advances in genetics and genomics have helped researchers understand how subtle genetic variations can drive the onset and development of disease - genetically validated targets are at least twice as likely to become registered medicines.
Typically, researchers start their efforts by identifying specific protein targets implicated in disease and then conduct recurrent screening of millions of chemical compounds against purified samples of these proteins. It then takes many months to identify the most promising compounds to take forward into drug development. Reactive fragment screening has the potential to simultaneously identify drug targets and prototype molecules, which can control target function in cells.
The technology is based on the use of ‘fragments’, essentially stripped-down versions of drug molecules, which in this application can be screened rapidly and directly in human cells. Then, highly sensitive analysis using mass-spectrometry based ‘chemoproteomics’, is used to build a map of the specific interacting proteins, which are captured by each fragment molecule in a disease-relevant context.
This technology could enable protein targets to be advanced into full drug discovery at a faster pace and with higher levels of confidence than previously possible.
Simon Boulton, Group Leader and project lead at the Crick, said: “By adopting advanced computational techniques, we can combine our genetic and chemical understanding of disease-causing proteins, to accelerate the development of new treatments.
“We already have plans in place to work with diverse groups from across the institute to employ this technology in a variety of disease settings, from identifying fragments that cause loss of viability in cancer cells, to exploring significant targetable proteins in malaria infection.”
Business Secretary Kwasi Kwarteng said: “As we build back better through innovation, we are putting the funding and structures in place so those at the top of their field – in business, research and academia – can develop world class products and technologies that could change all our lives for the better. The partnerships we are throwing our weight behind today all have innovation at their core.
“When I visited the Francis Crick Institute this week, it was fantastic to see their ongoing work with GSK to speed up the development of new medicines. The coronavirus pandemic has taught us how vital collaboration is between industry and science and I hope partnerships like this will help in our efforts to prepare for and respond to future pandemics.
“By bringing together business and research expertise in regions across the UK, we will help to drive local economic growth and create highly skilled jobs, all while cementing the UK’s status as a science superpower.”
Tony Wood, Senior Vice President of Medicinal Science & Technology at GSK, said: “Industrialising this technology expands our work with the Crick and directly supports GSK’s R&D ambition to improve industry success rates by developing more genetically validated targets. Together we will integrate cutting-edge functional genomics and machine learning technologies with next generation chemistry to identify novel targets and help more patients.”
This Prosperity Partnership builds on the Crick’s connections with GSK through our pre-competitive Biomedical LinkLabs. GSK scientists are embedded within the Crick, providing invaluable insight into translational science and benefitting from the world class fundamental research in our labs.
Veronique Birault, Director of Translation at the Crick, said: “This partnership exemplifies the future of biomedical research, where translation is accelerated by the convergence of industry and academia expertise and integrated collaborative work.
“Reactive fragment screening has the potential to revolutionise the discovery of new treatments and we are grateful to EPSRC and GSK for taking this pioneering step with us.”