Dr Gary Mirams
Sir Henry Dale Fellow
College Lecturer, Pembroke College
Room 361, Wolfson Building, Parks Road, Oxford OX1 3QD
My research is in computational biology, we construct mathematical models to describe biological processes. We aim to explore and explain biological processes and provide predictions about the behaviour of biological systems.
Please click for a list of my publications, conference proceedings and talks .
Drug-induced cardiac safety concerns
I worked on an NC3Rs / EPSRC Strategic Award in Mathematics in Toxicology entitled "Prediction of human cardiotoxic QT prolongation using in vitro multiple ion channel data and mathematical models of cardiac myocytes" - press release and project outline here. This project was in collaboration with GlaxoSmithKline and AstraZeneca modelling and safety pharmacology departments, we investigated whether mathematical models can provide more accurate early predictions of novel compounds' human clinical cardiac safety than existing preclinical animal-based tests. I worked with David Gavaghan, Blanca Rodriguez and Denis Noble.
I am also interested in different models of drug action, looking at where a simple conductance block model is appropriate, and cases where more detailed models of state-dependent, voltage-dependent and allosteric block are required. I am investigating which protocols suffice to fit which parameters in the ion-channel models, and where simplifications can be made.
In the past I have received funding from a GlaxoSmithKline Grants and Affiliates award to develop a simulation tool for prediction of drug-induced pro-arrhythmic risk, and to evaluate its predictive power. From 2008-2011 I worked on a European Commission project on "prediction of drug impact on cardiac toxicity" (PreDiCT), a video summarising some of the results can be seen on the right. A report on a recent workshop with pharmaceutical regulators, including the EMA and FDA, can be found here.
Our work on extending early pharmacological safety testing to better predict Torsadogenic risk has been published in Cardiovascular Research, and the codes used are available to download in an open-source format from the Chaste website.
As part of my research I am involved with the development of the Chaste computational biology environment along with members of the Computational Biology Group. I also work as a visiting researcher in systems biology with Peter Kohl's group at the National Heart and Lung Institute's Heart Science centre at Harefield Hospital, London. I am also an associate fellow with the 2020 Science programme, developing new ways of performing computational science with UCL and Microsoft Research.
Kylie Beattie - in partnership with GlaxoSmithKline, Kylie is attempting to use early ion-channel screening data to predict the results of later animal-based safety tests, with the aim of refinement, reduction and replacement. She is working on new protocols to improve the identification of the detailed kinetics of drug action on the hERG channel.
Beth McMillan - Beth is examining mechanisms behind early- and late-after depolarizations, and examining whether this tells us more about the likelihood of a drug compound inducing arrhythmias than simply prolongation of electrical activity in terms of APD or QT interval.
Louise Bowler - in partnership with Kate Harris and Jim Louttit at GlaxoSmithKline, Louise is developing simulations of stem-cell derived cardiomyocytes to enable comparison of expected drug action with that observed in experiments.
John Walmsley - investigated the role of heterogeneities and variability in cardiac electrophysiology models, he is now doing a postdoc at Maastricht University.
1st Year Introductory Calculus.
1st Year Dynamics.
A guide to using BibTex here.
Auxin signalling in Arabidopsis
My PhD was based at the Centre for Mathematical Medicine and Biology, Nottingham University on the impact of Wnt signalling on colorectal cancer initiation. I worked with Helen Byrne and John King as part of the Integrative Biology Project. As part of this I was involved in the development of a novel multiscale crypt model which was used to study monoclonal conversion in the colorectal crypts. A link to my thesis can be found on my publications page. At the beginning of my studies I attended the Oxford Life Sciences Interface Doctoral Training Centre.
For my undergraduate degree I studied mathematics with engineering at the University of Nottingham
Prediction of Thorough QT study results using action potential simulations based on ion channel screens
GR Mirams‚ MR Davies‚ SJ Brough‚ MH Bridgland−Taylor‚ Y Cui‚ DJ Gavaghan and N Abi−Gerges
In Journal of Pharmacological & Toxicological Methods. Vol. accepted‚ in press. 2014.
Ten simple rules for effective computational research
Osborne J.M. Bernabeu M.O. Bruna M. Calderhead B. Cooper J. Dalchau N. Dunn S−J. Fletcher A.G. Freeman R. Groen D. Knapp B. McInerny G.J. Mirams G.R. Pitt−Francis J. Sengupta B. Wright D.W. Yates C.A. Gavaghan D.J. Emmott S. and C. Deane
In PLoS Computational Biology. Vol. 10. No. 3. Pages e1003506. 2014.
Variability in high−throughput ion channel screening data and consequences for cardiac safety assessment
Ryan C. Elkins‚ Mark R. Davies‚ Stephen J. Brough‚ David J. Gavaghan‚ Yi Cui‚ Najah Abi−Gerges and Gary R. Mirams
In Journal of Pharmacological and Toxicological Methods. Vol. 68. No. 1. Pages 112−122. 2013.