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Gary Mirams

Personal photo - Gary Mirams
Dr Gary Mirams
Sir Henry Dale Fellow
College Lecturer, Pembroke College
gary.mirams@cs.ox.ac.uk

Room 361, Wolfson Building, Parks Road, Oxford OX1 3QD

Interests

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 ResearcherID .

I have a cardiac modelling blog, and a general twitter account: . More information on various topics I am working on is below.

Drug-induced cardiac safety concerns

A video featuring our work on cardiac safety.

I am currently funded by the Wellcome Trust and Royal Society on a Sir Henry Dale Fellowship.

A Nature Reviews Drug Discovery news article and a Nature SciBx article contain some of my comments on the FDA's recent proposed changes to drug-induced pro-arrhythmia testing.

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.

A video summarising our work on the preDiCT project

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.

Students

Current students

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.

Past students

John Walmsley - investigated the role of heterogeneities and variability in cardiac electrophysiology models, he is now doing a postdoc at Maastricht University.


Teaching

I hold a stipendiary lectureship in mathematics at Pembroke College, Oxford. I am currently teaching:

1st Year Introductory Calculus.

1st Year Dynamics.


Other Stuff

A guide to using BibTex here.

Gary's Holiday Snaps

Other Stuff


Biography

Auxin signalling in Arabidopsis

In 2008 I worked with John King in Nottingham, and Stefan Kepinski in Leeds on modelling the auxin signalling pathway in Arabidopsis roots (see my publications page for a paper on this topic).

Colorectal Cancer

Action Potentials under drug action
Simulating monoclonal conversion using a model of a colorectal crypt

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


Selected Publications

View all

Manage publications

Application of stochastic phenomenological modelling to cell−to−cell and beat−to−beat electrophysiological variability in cardiac tissue (in press)

John Walmsley‚ Gary Mirams‚ Joe M Pitt−Francis‚ Blanca Rodriguez and Kevin Burrage

In Journal of Theoretical Biology. 2014.

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.

Info

Themes

Activities

Projects

Completed Projects

Current Students

Past Student

Personal photo - John Walmsley
John Walmsley

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