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Mechanistic Modelling of PAR Polarity

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  • Full or part time
    Dr N Savage
    Dr J Rodriguez
  • Application Deadline
    No more applications being accepted
  • Competition Funded PhD Project (European/UK Students Only)
    Competition Funded PhD Project (European/UK Students Only)

Project Description

In eukaryotic cells, the PAR polarity proteins are core players in cell shape control and maintenance. Cell function is dependent on cell shape, and the mechanisms controlling cell shape are hijacked or altered in many diseases. For example: In cancer the ‘healthy’ function of PAR polarity proteins are altered to promote the spread of cancerous cells. Alzheimer’s patients have increased levels of some PAR proteins leading to ‘Tau tangles’ within diseased neuronal cells, hindering normal function. Reduced levels of particular PAR proteins disrupts intestine organisation, causing inflammatory bowel disease. There are many more examples of PAR polarity disruption in disease. Thus, a deeper understanding of the molecular mechanisms controlling PAR polarity would provide new inroads to treatment.

Within this project the successful candidate will work with the interdisciplinary supervisory team to generate and analyse mathematical/computational models of the PAR polarity network. Modelling results will be used to make predictions about protein interactions. The student will be integral in the design of experiments to test hypotheses generated by their modelling data (dry). Experimental data will be fed back into model design (wet). Wet-dry cycles will form an iterative process, the results of which will lead to a deeper understanding of the mechanisms under question.

Applicants with a degree in any scientific discipline will be considered. Students with degrees in subjects other than mathematics, physics, engineering or computer science must have strong evidence of interest and achievement in mathematics and/or computation.

Applicants are encouraged to contact Dr Savage to find out more. Email: [Email Address Removed]

HOW TO APPLY
Applications should be made by emailing [Email Address Removed] with a CV (including contact details of at least two academic (or other relevant) referees), and a covering letter – clearly stating your first choice project, and optionally 2nd and 3rd ranked projects, as well as including whatever additional information you feel is pertinent to your application; you may wish to indicate, for example, why you are particularly interested in the selected project(s) and at the selected University. Applications not meeting these criteria will be rejected.
In addition to the CV and covering letter, please email a completed copy of the Additional Details Form (Word document) to [Email Address Removed]. A blank copy of this form can be found at: https://www.nld-dtp.org.uk/how-apply.

Funding Notes

This is a 4 year BBSRC studentship under the Newcastle-Liverpool-Durham DTP. The successful applicant will receive research costs, tuition fees and stipend (£15,009 for 2019-20). The PhD will start in October 2020. Applicants should have, or be expecting to receive, a 2.1 Hons degree (or equivalent) in a relevant subject. EU candidates must have been resident in the UK for 3 years in order to receive full support. Please note, there are 2 stages to the application process.

References

(2012) Mechanistic mathematical model of polarity in yeast. Molecular Biology of the Cell, 23(10), 1998-2013

[(2013) Tracking Shallow Chemical Gradients by Actin-Driven Wandering of the Polarization Site. Current Biology, 23(1), 32-41. doi:10.1016/j.cub.2012.11.014

(2016) Parallel Actin-Independent Recycling Pathways Polarize Cdc42 in Budding Yeast. CURRENT BIOLOGY, 26(16), 2114-2126. doi:10.1016/j.cub.2016.06.047

(2015) Role of competition between polarity sites in establishing a unique front. ELIFE, 4. doi:10.7554/eLife.11611

(2015) Superresolution microscopy reveals a dynamic picture of cell polarity maintenance during directional growth. SCIENCE ADVANCES, 1(10). doi:10.1126/sciadv.1500947

(2013) Daughter Cell Identity Emerges from the Interplay of Cdc42, Septins, and Exocytosis. Developmental Cell, 26, 148-161.

(2013) Interaction between bud-site selection and polarity-establishment machineries in budding yeast. Philosophical Transactions of The Royal Society B, 368(1629)

(2009) Singularity in Polarization: Rewiring Yeast Cells to Make Two Buds. Cell, 139(4), 731-743. doi:10.1016/j.cell.2009.10.024

(2017) aPKC Cycles between Functionally Distinct PAR Protein Assemblies to Drive Cell Polarity. Dev. Cell, 2017 pp. 1-35

(2013) Systematic genetic interaction screens uncover cell polarity regulators and functional redundancy. Nat. Cell. Biol., 2013 vol. 15 (1) pp. 103-112



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