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How do cell identity factors contribute to cytokinesis?


   Department of Biosciences

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  Dr T Davies, Dr J Rodriguez, Prof Alistair McGregor  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

About the Project

Background: Cytokinesis, the physical division of one cell into two, is fundamental to life and errors can result in abnormal chromosomal numbers, developmental defects, and cancers. In order to divide, animal cells build an actomyosin contractile ring at the equator that constricts and divides the cell1. Similarities in the structural and molecular organization of the division apparatus in a variety of model systems give the impression that the mechanisms underlying division are shared between cell and organism types. However, work in the early embryo of the nematode worm Caenorhabditis elegans has shown that the requirement for key cytokinetic proteins varies between specific cell types in the early C. elegans embryo. At the four-cell stage, two specific cells are frequently able to divide when formin (an actin polymerase) is inhibited, or f-actin itself is disrupted. Given the central role of an actin based contractile ring in cytokinesis, this is surprising as is suggests that some cell types (in this case, the EMS and P2 cells) are able to divide even in absence of a normal contractile ring, while others (the ABa and ABp cells) show the typical requirement for formin and f-actin.

Aims: As the P2 cell gives rise to the C. elegans germline, its identity is controlled by a unique range inherited factors and regulated gene expression. By disrupting the factors that control P2 cell identity, this project will test if they promote successful cytokinesis in the P2 cell, investigate how they may alter the localisation of contractile ring components, and explore if these features are conserved in mammalian cells.

Methodology, techniques and training: Genetic and pharmacological tools will be used to disrupt protein function and modify cell identity, while fluorescence microscopy will be used to image the cells as they divide. Therefore, this project will provide training in these key techniques, as well as general C. elegans genetics and mammalian cell culture. The software ImageJ will be used to analyse dynamic cellular behaviours – both the progression through cytokinesis and the localisation of fluorescently tagged proteins. General molecular biology techniques (cloning, PCR, etc.) will be used as needed. Opportunities to present your work at internal seminars and external conferences will allow you to develop presentation skills and connect with the wider scientific community.

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);

·        a covering letter – clearly stating your first choice project, and optionally 2nd ranked project, 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;

·        copies of your relevant undergraduate degree transcripts and certificates;

·        a copy of your IELTS or TOEFL English language certificate (where required);

·        a copy of your passport (photo page).

A GUIDE TO THE FORMAT REQUIRED FOR THE APPLICATION DOCUMENTS IS AVAILABLE AT https://www.nld-dtp.org.uk/how-apply. Applications not meeting these criteria may be rejected.

In addition to the above items, please email a completed copy of the Additional Details Form (as a Word document) to [Email Address Removed]. A blank copy of this form can be found at: https://www.nld-dtp.org.uk/how-apply.

Informal enquiries may be made to [Email Address Removed]

The deadline for all applications is 12noon on Monday 9th January 2023.

 


Funding Notes

Studentships are funded by the Biotechnology and Biological Sciences Research Council (BBSRC) for 4 years. Funding will cover tuition fees at the UK rate only, a Research Training and Support Grant (RTSG) and stipend. We aim to support the most outstanding applicants from outside the UK and are able to offer a limited number of bursaries that will enable full studentships to be awarded to international applicants. These full studentships will only be awarded to exceptional quality candidates, due to the competitive nature of this scheme.

References

Cell-intrinsic and -extrinsic mechanisms promote cell-type-specific cytokinetic diversity. 2018 eLife 2018;7:e36204
Using fast-acting temperature sensitive temperature sensitive mutants to study cell division in Caenorhabditis elegans. 2017 Methods in Cell Biology (137) 283-306
High-Resolution Temporal Analysis Reveals a Functional Timeline 
for the Molecular Regulation of Cytokinesis. 2014 Developmental Cell (30) 209 – 223
Morphogenetic degeneracies in the actomyosin cortex. 2018 Elife 7:e37677
aPKC cycles between functionally distinct PAR protein assemblies to drive cell polarity. 2017 Developmental Cell (4):400-415.e9
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