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Actin regulation of nuclear mechanics during DNA repair

  • Full or part time
  • Application Deadline
    Applications accepted all year round
  • Self-Funded PhD Students Only
    Self-Funded PhD Students Only

Project Description

In eukaryotic cells, the nucleus houses the genomic material and transcription machinery that allows the cell to develop and perform its role. The nucleus is the largest and most rigid component of the cell therefore it dominates the whole cell mechanics. Therefore, knowledge of the mechanical properties of the nucleus, allows an assessment of whole cell mechanics and provides insight into the field of mechano-transduction. Nuclei mechanics are thought to be determined by the protein lamina and chromatin. The lamina is physically connected to the cytoskeleton therefore the nuclei shape will depend on the forces generated by the cell. Moreover, there is a correlation between nuclei stiffness and transcription activity whereby the nucleus is termed a mechanosensor.

Atomic force microscopy is rapid and sensitive to small changes in the mechanical properties throughout the nucleus. Now we wish to apply the methodology to study the consequence of DNA damage and how nuclear actin filaments (NAFs) upon the overall mechanics. NAFs form in response to DNA damage and they are required for repair to occur. We hypothesize that NAFs can perturb the nuclei mechanics. This will bring about a change in nuclei stiffness and/or a change in the mechanical response of nuclei. An increase in nuclear stiffness would lead to less migration, reduce mechano-sensitivity and therefore halt cellular processes until DNA repair has occurred. This could provide a strong protection mechanism for the cell.

To complement the AFM measurements, we will perform live cell imaging to explore the temporal stability of the filaments in relation to when DNA repair occurs in the cell.

Funding Notes

Entry Requirements:
Candidates must have a first or upper second-class honors degree or equivalent overseas qualification in a relevant subject.

Enquiries:
Interested candidates should in the first instance contact Dr Chris Toseland

How to apply:
Please complete a University Postgraduate Research Application form available here: View Website

Please clearly state the prospective main supervisor in the respective box and select ‘Department of Oncology and Metabolism’ as the department.

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