Assessing the effect of a novel cardiac drug on muscle mechano-energetics: experiments and mathematical modelling
Masters Project
The selective cardiac myosin activator omecamtiv mecarbil (OM) is a novel therapeutic agent that can increase cardiac muscle force production. In doing so, it can improve the systolic function of patients with heart failure.
At the cellular level, OM interacts directly with the contractile machinery (myosin). It can increase the fraction of myosin that is in the force-generating state, and can maintain that state for longer, without increasing cellular calcium and oxygen consumption. This suggests that OM confers an energetic advantage to the muscle in terms of increasing cardiac efficiency. However, this ‘advantage’ remains controversial as some studies report reduced efficiency albeit under a restricted set of loading conditions. A comprehensive understanding of the effects of OM on cardiac efficiency is critical for determining its suitability as a therapeutic agent for patients with heart disease.
The aim of this project is to understand the effects of OM on cardiac mechano-energetics using quantitative mathematical modelling and state-of-the-art muscle tissue experimentation. In this project, you will learn to perform sophisticated experiments on isolated muscle tissues using our world-leading custom-built work-loop calorimeter device, and to build advanced mathematical models to simulate how OM affects muscle function.
Desired skills
- Some experience with wet-lab experiments and mathematical modelling is preferred.
- Motivation to learn and develop new skills is essential.
Contact and supervisors
Contact/Main supervisor
Supporting supervisor(s)
- June-Chiew Han
Page expires: 2 January 2025