EPSRC Centre for Doctoral Training in Automated Chemical Synthesis Enabled by Digital Molecular Technologies

Lead Research Organisation: University of Cambridge
Department Name: Chemistry

Abstract

Efficient synthesis remains a bottleneck in the drug discovery process. Access to novel biologically active molecules to treat diseases continues to be a major bottleneck in the pharmaceutical industry, costing many lives and many £millions per year in healthcare investment and loss in productivity. In 2016, the Pharmaceutical Industry's estimated annual global spend on research and development (R&D) was over $157 billion. At a national level, the pharmaceutical sector accounted for almost half of the UK's 2016 £16.5bn R&D expenditure, with £700 million invested in pre-clinical small molecule synthesis, and 995 pharmaceutical related enterprises (big pharma, SMEs, biotech & CROs) employing around 23,000 personnel in UK R&D. The impact of this sector and its output on the nation's productivity is indisputable and worthy of investment in new approaches and technologies to fuel further innovation and development.

With an increasing focus on precision medicine and genetic understanding of disease there will be to a dramatic increase in the number of potent and highly selective molecular targets; identifying genetically informed targets could double success rates in clinical development (Nat. Gen. 2015, 47, 856). However, despite tremendous advances in chemical research, we still cannot prepare all the molecules of potential interest for drug development due to cost constraints and tight commercial timelines. By way of example, Merck quote that 55% of the time, a benchmarked catalytic reaction fails to deliver the desired product; this statistic will be representative across pharma and will apply to many comparable processes. If more than half of the cornerstone reactions we attempt fail, then we face considerable challenges that will demand a radical and innovative a step change in synthesis. Such a paradigm shift in synthesis logic will need to be driven by a new generation of highly skilled academic and industry researchers who can combine innovative chemical synthesis and technological advances with fluency in the current revolution in data-driven science, machine learning methods and artificial intelligence. Synthetic chemists with such a set of skills do not exist anywhere in the world, yet the worldwide demand for individuals with the ability to work across these disciplines is increasing rapidly, and will be uniquely addressed by this proposed CDT. By training the next generation of researchers to tackle problems in synthetic chemistry using digital molecular technologies, we will create a unique, highly skilled research workforce that will address these challenges and place UK academic and industrial sectors at the frontier of molecule building science.

The aspiration of next-generation chemical synthesis should be to prepare any molecule of interest without being limited by the synthetic methodologies and preparation technologies we have relied on to date. Synthetic chemists with the necessary set of such skills and exposure to the new technologies, required to innovate beyond the current limitations and deliver the paradigm shift needed to meet future biomedical challenges, are lacking in both academia and industry.

To meet these challenges, the University of Cambridge proposes to establish a Centre of Doctoral Training in Automated Chemical Synthesis Enabled by Digital Molecular Technologies to recruit, train and develop the next generation of researchers to innovate and lead chemical synthesis of the future.

Planned Impact

Who might benefit from this research? How might they benefit from this research?

Students
(a) The major beneficiaries of the CDT will, of course, be the students that train on the program. They will be equipped with a set of skills that will be highly desirable in the organic molecule making industries. Although the proposal is directing towards a need in the pharmaceutical industry, the training and research skills are totally transferable to industries like the argochemical sector (this is an almost seamless transition as the nature of the needs are near identical to that of pharma) but also the fine chemicals industries, CRO's who serve all of these industries. With some adaptation of the skills accrued then the students will also be able to apply their knowledge to problems in the materials industries, like polymers, organic electronics and chemical biology.

(b) Synthesis will also be evolving in academia and students equipped with skills in digital molecular technologies will be at a significant advantage in being apply to implement the skills acquired while training on the CDT. These students could be the rising stars of academia in 10 years time.

(c) The non-research based training will benefit the students by providing a set of transferable skills that will see them thrive in any chosen career.

(d) The industry contacts that will be generated from the variety of interactions planned in the CDT will give students both experience and insight into the machinations of the industrial sector, helping them to gain a different training experience (form industry taught courses) and hands on experience in industrial laboratories.

(e) All student in UCAM will be able to benefit in some way form the CDT. Training courses will not be restricted to CDT students (only courses that require payment will be CDT only, and even then, we will endeavour to make additional places available for non-CDT students). The overall standard of training for all students wil be raised by a CDT, meaning that benefit will be realised across the students of the associated departments. In additional, non CDT students can also be inspired by the research of the CDT and can immerse new techniques into their own groups.

Academic researchers in related fields (PIs)
(a) new research knowledge that results from this program will benefit PIs in UCAM and across the academic community. All research will be pre-competitive, with any commercial interests managed by Cambridge Enterprise

(b) a change in mnidset of how synthetic research is carried out

(c) new collaborations will be generated withing UCAM, but also externally on a national and international level.

(d) better, more closely aligned, interactions with industry as a result of knowledge transfer

(e) access to outstanding students

Broader public
(a) in principle, more potential medicines could be made available by the research of this CDT.

Economy
(a) a new highly skilled workforce literate in disciplines essential to industry needs will be available
(b) higher productivity in industry, faster access to new medicines
(c) spin out opportunities will create jobs and will stimulate the economy
(d) automation will not remove the need for skilled people, it will allow the researchers to think of solutions to the problems we dont yet understand leading to us being able to discover solutions faster

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
EP/S024220/1 31/05/2019 30/11/2027
2276995 Studentship EP/S024220/1 30/09/2019 29/09/2023 Daniel Wigh
2276523 Studentship EP/S024220/1 30/09/2019 31/12/2022 Rory Geeson
2276993 Studentship EP/S024220/1 30/09/2019 29/09/2023 Milo Smith
2276992 Studentship EP/S024220/1 30/09/2019 29/09/2023 Oliver Griffiths
2276986 Studentship EP/S024220/1 30/09/2019 29/09/2023 Elena Gelzinyte
2468554 Studentship EP/S024220/1 30/09/2020 29/09/2024 Thomas Wharton
2468412 Studentship EP/S024220/1 30/09/2020 29/09/2024 Joseph Phelps
2468566 Studentship EP/S024220/1 30/09/2020 29/09/2024 Katarzyna Zator
2468409 Studentship EP/S024220/1 30/09/2020 29/09/2024 Mia Kapun
2468368 Studentship EP/S024220/1 30/09/2020 29/09/2024 Marcus Grocott
2468419 Studentship EP/S024220/1 30/09/2020 29/09/2024 Lars Schaaf
2468416 Studentship EP/S024220/1 30/09/2020 29/09/2024 James Robinson
2468366 Studentship EP/S024220/1 30/09/2020 29/09/2024 Hannah Adams
2638490 Studentship EP/S024220/1 30/09/2021 29/09/2025 Ruslan Kotlyarov
2638405 Studentship EP/S024220/1 30/09/2021 29/09/2025 Rachel Phillips
2638334 Studentship EP/S024220/1 30/09/2021 29/09/2025 Sarah Beaton
2638486 Studentship EP/S024220/1 30/09/2021 29/09/2025 Henrique Marcon
2638493 Studentship EP/S024220/1 30/09/2021 29/09/2025 Kevin Ballu
2638399 Studentship EP/S024220/1 30/09/2021 29/09/2025 Samuel Brookes
2638525 Studentship EP/S024220/1 30/09/2021 29/09/2025 Jack Sydenham
2638412 Studentship EP/S024220/1 30/09/2021 29/09/2025 Katie Beckwith
2638422 Studentship EP/S024220/1 30/09/2021 29/09/2025 Hanna Saik
2751540 Studentship EP/S024220/1 30/09/2022 29/09/2026 Rebekah West
2751535 Studentship EP/S024220/1 30/09/2022 29/09/2026 Domantas Kuryla
2751504 Studentship EP/S024220/1 30/09/2022 29/09/2026 Daniel Davies
2751501 Studentship EP/S024220/1 30/09/2022 29/09/2026 Markus Böcker
2751533 Studentship EP/S024220/1 30/09/2022 29/09/2026 Barbara Kraus
2751539 Studentship EP/S024220/1 30/09/2022 29/09/2026 Eszter Varga-Umbrich
2751532 Studentship EP/S024220/1 30/09/2022 29/09/2026 Francesco Ceccarelli
2751542 Studentship EP/S024220/1 30/09/2022 29/09/2026 Julia Stachyra
2751541 Studentship EP/S024220/1 30/09/2022 29/09/2026 Russell Woodger
2751497 Studentship EP/S024220/1 30/09/2022 29/09/2026 Cecilia Anderson
2751537 Studentship EP/S024220/1 30/09/2022 29/09/2026 Benjamin Sharma
2751538 Studentship EP/S024220/1 30/09/2022 29/09/2026 Paula Teeuwen
2895015 Studentship EP/S024220/1 30/09/2023 29/09/2027 Soleh Anderlini
2895016 Studentship EP/S024220/1 30/09/2023 29/09/2027 Miruna Cretu
2895022 Studentship EP/S024220/1 30/09/2023 29/09/2027 Kohl Ratkovich
2895024 Studentship EP/S024220/1 30/09/2023 29/09/2027 Michael Zhou
2895018 Studentship EP/S024220/1 30/09/2023 29/09/2027 Nathan Harmer
2895765 Studentship EP/S024220/1 30/09/2023 30/03/2027 Alina Lelke
2895017 Studentship EP/S024220/1 30/09/2023 29/09/2027 Darcy Emmet
2895023 Studentship EP/S024220/1 30/09/2023 29/09/2027 Peter Rukovansky
2895021 Studentship EP/S024220/1 30/09/2023 29/09/2027 Laurence Midgley