Notable Work Undertaken Prior To Joining CoMPLEX
Summer Studentship at Cancer Research UK
Microtubules exhibit dynamic properties which depend on complex nanoscale processes at the growing microtubule end where polymerisation occurs. Convolved model fitting methods have been used to achieve subpixel precision analysis to show that the EB1 protein acts as a microtubule maturation factor. Furthermore, a mechanistic description of EB1's effects on microtubule growth and catastrophe indicate that EB1 accelerates two conformational transitions intrinsic to microtubule structure resulting in faster polymerisation and more frequent catastrophes.
My contribution to this project was to simulate experimental images of microtubules with differently long tapered ends. Using these simulations we determined the maximum taper length observed in the experimental data. We subsequently determined that the observed changes in the distribution of EB1 binding sites could not be attributed solely to the presence of a tapered end thus confirming the requirement for an intermediate non-EB1 binding state in the microtubule lattice at the growing end.
Maurer SP, Cade NI, Bohner G, Gustafsson N, Boutant E, Surrey T. EB1 Accelerates Two Conformational Transitions Important for Microtubule Maturation and Dynamics. Curr. Biol. 24(4), 372-384 (2014); doi: 10.1016/j.cub.2013.12.042
MSci Physics Project - Monte Carlo Simulations of an F0F1 ATP Synthase Model: A Study of coupled Molecular Motors
Abstract from report.
A model for F0F1 ATP Synthase as two chemically driven ratchets with constant forward rates in opposing directions coupled by an elastic axle in a `tug of war' is proposed. A Monte-Carlo method is used to simulate the operation of this model to study the rate dependence on the free energy available to the F0 motor and the torsional rigidity of the axle. The rate of synthesis is found to agree quantitatively in the thermodynamic limit and in the maximum rate to experimental data. Good qualitative agreement is found away from these limits. Three Phases of operation are observed, a forward synthesis phase, a backward proton pumping phase and a locked phase. A mean field theory for the model is discussed and provides a basis for the onset of these phase transitions. A possible model for a rate limiting process with an analytical solution is proposed although not rigorously formulated. Auto-correlation and frequency analysis of the transition sequence identifies two operating regimes between which the model transitions smoothly at the phase transition. These are, a highly correlated regime characterized by alternate stepping and a single frequency peak in a low background of white noise, and an uncorrelated regime characterised by transition fluctuations which obey Brownian statistics.
The report for this project can be downloaded here.