This page contains a few brief descriptions of projects undertaken by current and previous students at the Systems Biology DTC.
Elizabeth McMillan, 2012 Intake
If you want to find out if a drug is going to cause a fatal arrhythmia, how would you go about it? In my DPhil project, I use mathematical models of single heart cells to predict dangerous drug effects. These models can tell you how the cell acts under different conditions, by linking the ionic currents that flow into and out of the cell to the voltage over the cell’s membrane. Usually, the membrane voltage only spikes once during every beat. However, if you perturb the currents into and out of the cell, you can make the voltage spike twice. These double spikes (or “after-depolarisations”) have been linked to the onset of arrhythmias. My question is: how much more or less do you have to perturb the cell to make it fire twice after you’ve added the effects of a drug? Do anti-arrhythmic drugs make it harder to create after-depolarisations, and do pro-arrhythmic drugs make it easier? If so, can we use this to predict arrhythmic risk? I’m trying to answer these questions using computer simulations and clinical data.
Will Smith, 2012 Intake
Biofilms incorporate a range of inter-woven physical, chemical and biological processes. In a confluent biofilm, interactions between constituent microbes are particularly significant: cells are in close physical contact, constantly pushing one another out of the way as they grow and divide. However, the effects that these mechanical interactions exert on film development are not yet well-understood for populations of non-spherical cells, such as P. aeruginosa or E. coli. The aim of my research is to develop, compare, and finally apply computer models to investigate how microbial cell shape affects the systems biology of a microbial colony, focussing on the emergence of spatial structure and its effects on microbial ecology.
Jonny Brookes-Bartlett, 2012 Intake
Determining the three-dimensional structure of macromolecules such as proteins is incredibly important, with a direct application being to aid the design of effective pharmaceutical drugs for medicinal purposes. X-ray crystallography is the most common technique to find the three-dimensional structure of proteins. This technique involves irradiating a crystal composed of the protein of interest with X-rays. The problem is that the X-rays cause damage to the molecule and degrades the data collected in the experiment which are required to solve the structure. For radiation sensitive proteins the damage can be so bad that the data are not interpretable and a structure solution can not be achieved. My research focuses on mathematically modelling the progression of the radiation damage using simulations of the experiment to estimate values for the energy that the crystal absorbs from the X-rays. These values can be used to better predict the useful lifetime of a protein crystal in an X-ray crystallography experiment, help with the design of optimal experimental strategies and potentially reconstruct damaged data to a theoretical undamaged state. The project involves a very nice balance between performing hands-on experiments in the lab and computational and theoretical modelling.