About the Project
The replication of DNA is executed by molecular machines called DNA polymerase, which travel along the DNA molecule as it replicates it. The DNA polymerases must be assembled from several molecules at the starting point of replication – specific locations on the DNA called replication origins. These precursor molecule move in the nucleus through Brownian motion, making this a stochastic process. Once assembled, they travel through the DNA, “unzipping” it into its component strands and performing the replication as it goes. Because the DNA polymerase is a molecular machine, it is subject to thermal fluctuations from the environment, which affects how it moves. To further complicate things, the DNA is a busy place: many processes are taking place in it at the same time, especially protein synthesis. So the DNA polymerases can collide with other molecules bound to DNA and get stuck for a while. For all those reasons, DNA replication is expected to be highly stochastic. However, most models assume that the DNA polymerases travel at constant speed on the DNA. We will formulate mathematical models taking the stochastic nature of the movement of DNA polymerases into account. We will create numerical simulations to test the predictions from our theory, and compare our results to experimental data available from collaborators. We will also examine the assembly of the DNA polymerases from its component molecules, and model its waiting-time statistics.
This project addresses some fundamental questions on the nature of DNA replication, and we expect it will have high impact in the field.
This project can be started as a distance learning PhD.
Applicants should have a background in Mathematics, physical sciences or computing science.
Applicants should hold (or expect to achieve) a UK honours degree at 2.1 or above (or equivalent) in Physics, mathematics, computer science, or similar degree with knowledge of statistical physics and stochastic processes and some experience of programming.
• Apply for Degree of Doctor of Philosophy in Physics
• State name of the lead supervisor as the Name of Proposed Supervisor
• State ‘Self-funded’ as Intended Source of Funding
• State the exact project title on the application form
When applying please ensure all required documents are attached:
• All degree certificates and transcripts (Undergraduate AND Postgraduate MSc-officially translated into English where necessary)
• Detailed CV
Informal inquiries can be made to Dr A Moura ([email protected]), with a copy of your curriculum vitae and cover letter. All general enquiries should be directed to the Postgraduate Research School ([email protected].
R Retkute, CA Nieduszynski, A de Moura (2011). Dynamics of DNA replication in yeast, Phys Rev Lett 107, 068103.
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