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How to make molecular machines: modelling ribosome biogenesis

  • Full or part time

    Prof I Stansfield
  • Application Deadline
    Applications accepted all year round
  • Self-Funded PhD Students Only
    Self-Funded PhD Students Only

Project Description

Ribosomes are arguably the most important biological molecular machines.

Cells can be seen as factories of proteins, with ribosomes being the machines producing them. Therefore, understanding how ribosomes themselves are made and how their production is controlled depending on the environment of the cell, is a fundamental question in cell biology. Despite of extensive information on the process of ribosome biogenesis gathered in recent years, the regulation of ribosome production upon changes in external cellular conditions remains an outstanding open question.

The main aim of this project is to develop a mathematical model of ribosome biogenesis taking into account the current knowledge about the biochemical pathways. In particular, we will aim at identifying the rate-limiting steps and most crucial mechanisms determining the production rate of ribosomes, as well as how this production can be finely tuned depending on external cellular resources and environmental conditions. We will also explore the links between the cell cycle and ribosome biogenesis, as well as metabolism. In contrast to a large mathematical model comprising a very high number of components, our objective is to develop a model as simple as possible, but nevertheless predictive, so that it allows us gaining insight into the fascinating process of ribosome biogenesis.

The PhD student will work in a dynamic and interdisciplinary team of researchers working at the interface between physics and biology, integrating theoretical and experimental results.

Candidates should have (or expect to achieve) a UK honours degree at 2.1 or above (or equivalent) in Physics or Applied Mathematics or Chemical/Bioengineering along with knowledge of Differential equations, statistical physics; knowledge/interest in dynamical systems, stochastic systems, modelling of biological systems.

APPLICATION PROCEDURE:

• 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
• Details of 2 academic referees

Informal inquiries can be made to Prof M Carmen Romano () with a copy of your curriculum vitae and cover letter. All general enquiries should be directed to the Postgraduate Research School ()


Funding Notes

This project is advertised in relation to the research areas of the discipline of physics/applied mathematics. The successful applicant will be expected to provide the funding for Tuition fees, living expenses and maintenance. Details of the cost of study can be found by visiting View Website. THERE IS NO FUNDING ATTACHED TO THESE PROJECTS

References

[1] M. C. Romano, M. Thiel, I. Stansfield, and C. Grebogi, “Queueing Phase Transition: Theory of Translation”, Phys. Rev. Lett. 102, 198104 (2009).

[2] C. A. Brackley, M. C. Romano, C. Grebogi, and M. Thiel, “Limited Resources in a Driven Diffusion Process”, Phys. Rev. Lett. 105, 078102 (2010).

[3] C. A. Brackley, M. C. Romano, and M. Thiel, “The Dynamics of Supply and Demand in mRNA translation”, PLoS Comput. Biol. 7, e1002203 (2011).

[4] Ciandrini, L., Stansfield, I. & Romano, MC. (2013). 'Ribosome traffic on mRNAs maps to gene ontology: genome-wide quantification of translation initiation rates and polysome size regulation'. PLoS Computational Biology, vol 9, no. 1, e1002866.

[5] Marshall, E., Stansfield, I., and Romano, M.C. (2014) “Ribosome recycling induces optimal translation rate at low ribosomal availability”, J. R. Soc. Interface 11: 20140589

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