“The more academics can help our industrial colleagues, the more impact we can have in producing improved medicines”

A pharmacologist at St John’s has been awarded a prestigious Royal Society Industry Fellowship to work with AstraZeneca on developing life-changing medicines.

The fellowship will enable Dr Graham Ladds to be seconded for four years to AstraZeneca, which was among the first in the world to produce a Covid-19 vaccine with scientists at the University of Oxford.

Dr Ladds, who is a Fellow of St John’s and Reader in Receptor Pharmacology at the University of Cambridge, will work part-time across the Genome Editing and Bioassay Development teams at AstraZeneca’s labs in Cambridge to drive improvements in drug effectiveness and reduce the chances of side effects.

“The ultimate idea is to try to make safe drugs and drugs that have high efficacy,” said Dr Ladds. “All drugs come with associated side effects. That's the biggest problem for any drug discovery programme. The pharmaceutical industry would ideally like a drug that you can give to somebody that only does what it's supposed to do, without any problems.”

Often the side effects of drugs are mild, but sometimes they can be severe and require further medication to combat the symptoms. Dr Ladds will be investigating why side effects occur and how to stop them happening. One way is by studying the actions of G protein-coupled receptors (GPCRs).

GPCRs are receptors that enable cells to sense chemical substances such as hormones, fragrances and drugs in their environment. The cells read their environment and sense the levels of hormones such as adrenalin, serotonin, histamine and dopamine. They can also act as light, smell and flavour receptors, with some located in the eyes and on the tongue.

Humans have around 800 different GPCRs in our bodies and about half of all drug therapies act using these receptors – including beta blockers for heart conditions and blood pressure, antihistamines for allergies, and psychiatric drugs. But not enough is known about how GPCR signalling works.

In many studies, cells are manipulated to enable their rapid growth under laboratory conditions, which means they lose any relationship with native – or ‘primary’ – cells.

“Despite decades of research on GPCR function, we still do not have a full understanding, at the molecular level, of how these fundamentally important molecules work. Consequently, by association, we cannot say that we fully understand how most drugs act upon GPCRs,” said Dr Ladds.

“Here in collaboration with AstraZeneca, we aim to make use of recent advances in genome editing, using native human cells, combined with the development of highly sensitive readouts of signalling to generate novel cell lines that faithfully report the nuances of GPCR signalling events.

“These cell lines will represent vital new tools to drive improvements in drug effectiveness and thereby reducing off-target actions often associated with unwanted side effects."

The Industry Fellowship is part of the Royal Society's wider Science and Industry Programme, which strives to promote the value and importance of science by connecting academia, industry and government.

Dr Ladds, who is currently on a research sabbatical leave, is looking forward to straddling academic research and industry when he takes up his fellowship in March 2022.

“I’m a pharmacologist, we find out how drugs work and we design new drugs, and I think the more academics can help our industrial colleagues, the more impact we can have in producing improved medicines,” he added.

Find out about the Royal Society Industry Fellowships

Published 7/10/2021

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