A mathematical biologist at the University of Nottingham has received funding of over £1.9m from Wellcome to develop mathematical models to test whether new pharmaceutical drugs will have side-effects on the heart.
Dr Gary Mirams, currently a Wellcome & Royal Society Sir Henry Dale Fellow in the Centre for Mathematical Medicine & Biology in the School of Mathematical Sciences, has spent much of his academic career working on simulations of cardiovascular biology – creating mathematical models of the heart and software packages to run simulations that allow pharmaceutical companies to test the safety of new drugs on the heart. His research has helped change the way new drugs are tested and made a significant reduction in the number of animal-based cardiac safety experiments.
Dr Mirams said: “Our work to date has proved the usefulness of cardiac simulations in assessing drug safety for the heart. It has also made good progress in improving the reliability of models for this application. But simply making predictions is not good enough for use in safety-critical situations: developing models reproducibly, tracking the derivation of their choice of equations and parameter sets from data, and quantifying our uncertainty in their predictions is also crucial. My Wellcome Senior Research Fellowship will advance this research agenda for cardiac electrophysiology models in drug safety studies.”
Tackling the most important questions in science
Wellcome’s Senior Research Fellowships support independent researchers who want to tackle the most important questions in science and who are leaders in their field. Dr Mirams’ research aims to increase our understanding of the electrophysiology of the heart, pushing the boundaries in mathematical modelling and its biological applications.
The heartbeat is co-ordinated by proteins that bind together in cell membranes and allow electrically-charged ions to pass through them – structures known as ion channels. When new pharmaceutical drug compounds are developed, they can interfere with the heart’s rhythm because they bind to and block ion channels. This unwanted side effect – heart arrhythmia - can be fatal.
Dr Mirams looks at why and how certain drugs cause these problems and aims to create an accurate picture of safety – screening out pro-arrhythmic risk - for each new drug before it is given to patients. To do this his team uses mathematical models for electrical activity of heart cells to integrate data from safety tests and predict overall risk.
Dr Mirams said: “We are designing and testing new experimental approaches to get more information for building our models more accurately and in less time. The aim is to make better predictions from easier-to-perform experiments that can be used routinely in early pharmaceutical testing.”
Dr Mirams will be collaborating with colleagues in the USA, France, the Netherlands, Australia and Switzerland. He will also be working closely with fellow academics in the Centre for Mathematical Medicine and Biology and Chris Denning, Professor of Stem Cell Biology in the School of Medicine.
Simulations developed by Dr Mirams are now being used in-house by two leading pharmaceutical companies. A public web-based interface to the simulations has more than 250 registered users including 9 of the 10 largest global pharmaceutical companies.
Dr Mirams’ work is supported by the University’s Research Priority Area ‘Data modelling and Uncertainty’.
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