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How does germline fate regulate C. elegans cell division?


   Department of Biosciences

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  Dr T Davies, Dr J Rodriguez, Dr D Weinkove  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

About the Project

Project Title: Investigating the role of germline fate in regulating C. elegans cell division

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 cell. 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 (including the germline precursor cell) can divide even in absence of a normal contractile ring.

Aims: This project will focus on aspects of the germline precursor cell that allow it to divide even when the contractile ring is weakened or damaged. As this cell (called 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, you will test if they promote successful cytokinesis in the P2 cell and investigate how they may regulate contractile ring components. You will then use tissue culture to compare how these factors may also regulate mammalian cell division.

Methodology, techniques and training: siRNA, genetic tools, transfection and inhibitors will be used to disrupt protein function and cell identity in C. elegans embryos and cultured mammalian cells, while confocal microscopy will be used to image both the progression through cytokinesis and the localisation of fluorescently tagged proteins.

You will be trained in these key techniques, as well image analysis software such as ImageJ. General molecular biology techniques (cloning, PCR, Westerns, 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.

See https://www.davieslab.org for information about the lab and please feel free to email Tim Davies ([Email Address Removed]) for more details about the project or lab.

The studentship should be commenced before the end of 2022.

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 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.

The closing date for applications is Friday 8th July 2022 at 12noon (UK time).


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. Note that home (UK) candidates may also apply to this studentship.

References

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