Introduction

The Next Generation Chemistry for Medicine theme at the Rosalind Franklin Institute brings the techniques of organic chemistry to bear on living systems. By investigating natural mechanisms using chemical approaches, scientists can generate fresh insights into complex biology.

Professor Ben Davis leads the Next Generation Chemistry theme. For nearly two decades, his research group at Oxford University has focused on improving our chemical understanding of biomolecular structure and function – particularly in proteins and carbohydrates. The manipulation of these biomolecules has a host of potential biotechnological applications, including the development of new disease therapeutics.

Professor Davis says: ‘One of the things we’re deeply interested in at The Franklin is the notion of being able to program the functional information that is found in biological molecules like proteins, sugars or lipids. What we’re exploring is how to insert information precisely into these molecules to alter their function. Instead of “gene editing”, you might call it protein editing – and I can see it developing into a hugely exciting area.’

A recent avenue of particular interest to scientists in the Next Generation Chemistry theme is the use of light as a benign trigger for activating (or deactivating) biological function in proteins, making and breaking chemical bonds to alter the information inside these ‘workhorse’ molecules. Medicine is the natural direction for much of this work, with conceivable applications in drug and vaccine development, as well as the therapeutic use of protein editing itself through the enhancement of ‘deficient’ proteins or the introduction of synthetic proteins into the body. But, says Professor Davis, the generation of chemical insights into the field of biology will be of much broader benefit and applicability.

He says: ‘The sense of excitement around The Franklin is remarkable. People here are driven by an ethos of collaboration and a desire to solve fundamental problems in life science, which will be transformational in bringing a deep understanding of chemistry into the heart of biology and physiology.’

This collaborative, problem-solving approach has been demonstrated clearly during the coronavirus pandemic. An early question surrounding the SARS-CoV-2 virus was whether it might be exploiting carbohydrate molecules to enter hosts. With evidence unclear, scientists from The Franklin’s Next Generation Chemistry and Structural Biology programmes worked alongside international colleagues to unpick the problem and, in remarkably quick time, produced a new picture of the role of host carbohydrate interactions in COVID-19 infection.

Professor Davis adds: ‘There are real synergies with the other themes at The Franklin, such as Structural Biology, Correlated Imaging and Biological Mass Spectrometry, which offer great opportunities for collaboration. There are also significant opportunities around high-throughput methodologies in this type of chemistry, and the use of AI and machine learning techniques for algorithm-based discovery.’

Professor Ben Davis

Science Director, Next Generation Chemistry

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Theme Leader

Professor Ben Davis

Science Director, Next Generation Chemistry

Ben Davis got his B.A. (1993) and D.Phil. (1996) from the University of Oxford. During this time he learnt the beauty of carbohydrate chemistry under the supervision of Professor George Fleet. He then spent two years as a postdoctoral fellow […]

Post-translational mutagenesis and synthetic biologics

With this project, we aim to develop chemical editing tools for biological systems. Cellular processes, such as movement or cell-cell communication dominate many functions in higher organisms but are only understood in gross terms. Control of cells through the “editing” of functional biomolecules could allow reprogramming of events as diverse as inflammatory response to tissue formation.

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Mechanistic Proteomics

This project aims to understand mechanistic biology at the molecular level by examining the structure of key workhorse biomolecules. Multi-scale models suitable for precise biomolecule editing and programming and interrogation by widescale gene-product-omics will be established with a focus on the exploitation, control and understanding of chemical structure. One goal is to fully exploit the >4000 serum proteins that are predicted to exist as potential quantifiable biomarkers.

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High Throughput Drug Discovery Laboratory

The High Throughput Drug 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.

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