Model Cardiac Mechanics in Heart Failure

This PhD project is a potential Pfizer-sponsored studentship position at King’s College London to develop a Quantitative Systems Pharmacology simulation platform for evaluating the effects of pathological and pharmacological changes in subcellular function on whole organ cardiac physiology. The project will suit a candidate with a passion for applied mathematics, computer science and computational biology.

Background: Multi-scale computational models of the heart are increasingly being adopted by the pharmaceutical industry to simulate how pathologies and drugs acting on the cell alter whole organ cardiac function. These models mathematically describe the multiple coupled physical systems that lead an electrical signal propagating across the heart to initiate muscle contraction causing the heart to pump blood to the lungs and around the body. The resulting non-linear systems of equations are then solved numerically through the finite element method.

Aims: This project will use models that simulate cardiac function from the cell through to the whole organ to predict potential drug targets at the subcellular scale that treat the pathological changes in organ scale function that are characteristic of heart failure. Pre-clinical models of healthy and failing hearts will be developed and validated against predictions of drug effects on organ scale cardiac function. Results from the preclinical simulations will be applied to patient specific models of human hearts to predict similarities and discrepancies in cross-species drug effects.

Approach: This project will involve: processing, analysing and interpreting experimental and clinical data to infer model parameters and validate model predictions; image processing and mesh creation; non-linear parameter inference and multi-scale simulations using high performance computing resources. The cardiac models require the numerical solution of systems of differential equations to model cellular physiology and the monodomain and the large deformation elasticity partial differential equations for simulating cardiac electrophysiology and mechanics, respectively. The project will involve working closely with the BioMedical Engineering department at Kings’ College London and the Quantitative Systems Pharmacology group in Pfizer’s Internal Medicine Research Unit.

Candidate: A strong mathematical and programming background will be essential for this project. Experience with C/C++ (or equivalent), Linux, MPI, HPC and/or PETSc would be beneficial. The project is suited to a candidate with a background in biological modelling, cardiac research, large deformation mechanics, parameter inference, multi-scale simulations, image processing and/or the finite element method.

Profile page URL: http://www.cemrg.com

Supervisors: Dr Steven Niederer and Dr Anna Sher

Start date: 02/10/2017 (negotiable)

Contact information for enquiries: [Email Address Removed]