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 am also an associate fellow with the 2020 Science programme, developing new ways of performing computational science with UCL and Microsoft Research.
Kylie Beattie - is working on an Impact Acceleration Award in partnership with GlaxoSmithKline. She is applying new protocols to measure detailed kinetics of drug action on the hERG channel.
Sanmitra Ghosh - is working on how we select and parameterise cardiac electrophysiology models, at the cell and ion channel scales, and examining systematic ways to design experiments to assist with this.
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.
Ross Johnstone - in partnership with Liudmila Polonchuk and Mark Davies at Roche, and Remi Bardenet at Lille University, Ross is looking at how to tailor mathematical cardiac electrophysiology models to individual cells by using Bayesian Inference to inform experimental design to constrain the parameters we wish to calibrate on a cell-specific basis.
Kylie Beattie - in partnership with GlaxoSmithKline, Kylie used early ion-channel screening data to predict the results of later animal-based safety tests, with the aim of refinement, reduction and replacement. She also worked on new protocols to improve the identification of the detailed kinetics of the hERG channel.
John Walmsley - investigated the role of heterogeneities and variability in cardiac electrophysiology models, he is now doing a postdoc at Maastricht University.
Ken Wang - developed new methods to study cardiac electrophysiology on pseudo-2D cardiac tissue slices, to examine the cellular heterogeneity with different regions of the heart. She is now a Postdoctoral Research Fellow at Roche Safety Pharmacology group in Basel, Switzerland.
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
White Paper: Uncertainty and variability in computational and mathematical models of cardiac physiology (accepted‚ in press)
GR Mirams‚ P Pathmanathan‚ RA Gray‚ P Challenor and RH Clayton
In Journal of Physiology. 2016.
The Cardiac Electrophysiology Web Lab
Jonathan Cooper‚ Martin Scharm and Gary Mirams
In Biophysical Journal. Vol. 110. No. 2. Pages 292−300. 2016.
Uncertainty and variability in models of the cardiac action potential: can we build trustworthy models?
RH Johnstone‚ ET Chang‚ R Bardenet‚ TP de Boer‚ DJ Gavaghan‚ P Pathmanathan‚ RH Clayton and GR Mirams
In Journal of Molecular and Cellular Cardiology. 2016.