Welcome to Gary Mirams’ research homepage.
My research is in mathematical biology, constructing mathematical and computational models to describe biological processes. We aim to explore and explain biological processes and provide predictions about the behaviour of biological systems. I’m particularly interested in how we choose equations, put parameter values in them, how we might design experiments for doing this better, and making sure we have software tools for doing these things more reliably.
See my publications page for recent papers, colleagues page for students and postdocs that I’m working with, and links page for details of safety pharmacology and cardiac electrophysiology web portals.
Drug-induced cardiac safety concerns
I led 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”. 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.
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 was also an associate fellow with the 2020 Science programme, developing new ways of performing computational science with UCL and Microsoft Research.
Colorectal crypt modelling
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.