PhD project: How do cell identity factors contribute to cytokinesis? (Durham University)
Posted by Tim Davies, on 2 January 2023
Location: Durham, UK
Closing Date: 9 January 2023
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.
Application and PhD program details: The project is part of the BBSRC DTP3 program run by Durham, Liverpool and Newcastle Universities, and this project will be based at Durham University. Details on the application process can be found here (https://www.findaphd.com/phds/project/how-do-cell-identity-factors-contribute-to-cytokinesis/?p150329), or contact the lead supervisor (Dr Tim Davies – timothy.r.davies@durham.ac.uk). Deadline for applications is 9th of January
Closing Date: 9 January 2023
Scientific fields: Cell biology, Development and disease
Model systems: C. elegans, Human
Duration: Fixed term