David Fallaize - UCL CoMPLEX 2006-2011

David Fallaize

After gaining my MEng in Electrical/Electronic engineering at Cambridge University I worked for two years as a software developer before joining CoMPLEX where I completed an MRes (with distinction) in 2006-07 followed by a PhD at CoMPLEX/ISMB between 2007-11.

I submitted my PhD in September 2011 and am awaiting my viva examination.

PhD: Large-Scale Parallelised Boundary Element Method Electrostatics for Biomolecular Simulation

macromolecular crowding

All life is based on the interactions between biological molecules (e.g. proteins, nucleic acids), which in human cells coexist in a complicated and crowded mixture. It is extremely difficult to directly measure the interactions between individual biomolecules in the lab because of the very small length-scale and short time-scale over which these processes occur. Computer simulations which model these interactions can improve our understanding and suggest avenues for further experiment. With increased knowledge of how biomolecules interact comes better understanding of what happens in illnesses where biomolecules misbehave, and ultimately leads to progress in medical science and the treatment of disease.

In order to carry out large-scale simulations, we need to be able to calculate the electrostatic force between proteins (like that between a positive and negative charge). This can be found by solving the Poisson-Boltzmann Equation (PBE), but unfortunately the process is generally non-trivial.

acetylcholinesterase and fasciculin

I have written a program called BEEP which solves the linearised PBE using the "boundary element method" (BEM) with a linearly-scaling fast multipole method (FMM) . I improved and parallelised these highly complex algorithms, using a number of open source tools and libraries along the way (e.g. Boost, OpenCL, OpenMP). BEEP now runs on both desktop computers and HPC clusters, and uses GPUs to accelerate the near-field integration terms of the BEM.

Our results of running BEEP on proteins show that the stability and numerical accuracy of the combined BEM/FMM method is extremely sensitive to the choice of surface representation and integration method. I used a curved triangulated surface to improve numerical stability and accuracy, and conclude that it is practicable to use the total electrostatic solvation energy calculated by BEEP to drive a Monte-Carlo simulation of protein-protein interactions.

MRes: Modelling Biological Complexity

hippocampal neuron

CASE Essay 1: Motion tracking of fluorescently tagged receptor proteins

This essay discusses the experimental process of tracking the diffusion of GABAA receptors in the cell membrane of neuronal cells by fluorescent confocal microscopy, and the mathematical issues arising from the interpretation of the results – i.e. the motion tracking task of converting a video of the movement of blurry ‘blobs’ into estimates of underlying diffusion coefficient distribution.
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hepatocytes under a confocal microscope

CASE Essay 2: Simplification of biological models using Voronoi compression technique

This essay shows how phase plane analysis of biological models (in this case, the Morris-Lecar barnacle giant muscle fibre, and a model for hepatocyte calcium oscillations following Höfer) can be carried out using a novel Voronoi 'compression' technique. The result is simplification of the model without loss of useful information, such as location in phase space of fixed points, limit cycles etc.
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hypolimnas bolina

CASE Essay 3: Sperm modelling of butterflies

Bacterial infections such as the male-killing Wolbachia can infect butterflies and cause distortions in the operational sex ratio (OSR) of the population by increasing the number of females relative to males. The excess of females leads to increased opportunities for males to mate, and alters the optimum sperm allocation strategy. Mutant males who have a strategy which fertilises more eggs than will have an immediate advantage over rival males, and such mutations would be expected to fixate rapidly leading to fast evolution of sperm strategy towards the new optimum. This essay presents a model of both female and male mating behaviour which is solved using a method of dynamic programming combined with simulation to yield the optimal sperm strategy for a given initial OSR.
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Mars

MRes Summer Project: Modelling extraterrestrial radiation environments for astrobiology

This project is concerned with estimating the probability of bacteria being able to survive beneath the surface of Mars, given the harsh environmental conditions which exist there. To make such an estimate at least two things must be known: the level of ionizing radiation at the surface of Mars due to both solar and galactic radiation; and the capacity of biological material to survive the radiation. Correspondingly this project is divided into two parts: firstly the simulation of the radiation environment on Mars, using a Monte-Carlo simulation program based upon the Geant4 physics framework; secondly a set of biological experiments which aim to link the damage caused by desiccation to the damage caused by radiation, using Antarctic extremophile bacteria as proxies for hypothetical Martian bacteria.

The results of our desiccation experiments were published in Antarctic Science and are also available in the project report.

Metapopulation dynamics

A python application to simulate metapopulation dynamics: metapopulation.py

©2011 David Fallaize