Cell division is a fundamental biological process. Its complexities have been extensively studied and as such there is a wealth of knowledge concerning the signalling and mechanical processes required to carry it out. However, the majority of this work has been carried out in simple, 2D, in vitro systems. While this knowledge is invaluable it does not consider how cell division is conducted in the more complex and dynamic environments found in vivo, particularly during tissue and organ development. This project will further our understanding of a fundamental feature of cell division, namely the dynamic movements of the mitotic spindle, in a complex and motile in vivo system (zebrafish blood vessel development (angiogenesis)).
During cell division the positioning and orientation of the mitotic spindle determines the plane where the cytokinetic furrow will form. This ensures that the two daughter cells are the correct size and that they are “born” in the appropriate position. A breakdown of this process can disrupt metabolic processes (such as cell cycle regulation) and/or disrupt tissue morphology. Known spindle positioning/orienting mechanisms largely rely on a balance of forces which pull the mitotic spindle into the correct position. These have predominantly been described in cells which become spherical during division (mitotic rounding). This process generates a simple, symmetrical geometry, which is easily divided into two evenly sized daughter cells. However, we find that cells in several highly motile tissues (e.g. endothelial cells during angiogenesis, neural crest cells) maintain non-regular morphologies during mitosis.
The primary aim of this project therefore is to understand how the dynamics of the mitotic spindle are generated in cells of non-regular mitotic morphologies, primarily in endothelial cells during blood vessel development. These cells represent an ideal opportunity to investigate how cells dividing in vivo can deal with complex mitotic shapes or even exploit atypical mitotic cell geometry to modulate mitotic spindle movements and generate asymmetric cell divisions.
This project will use a multidisciplinary approach to answer this important question and will involve the use of live imaging to capture mitosis during zebrafish angiogenesis and in the chick neuroepithelium. The data generated from this cutting-edge microscopy will be used to parametrise an in silico model currently being developed in the University of Rochester, USA. This model will allow the exploration of the mechanical processes necessary to generate in vivo mitotic spindle dynamics. The hypotheses generated will then be tested in vivo using transgenic, optogenetic and/or laser ablation approaches.
Eligibility
Applicants must have obtained or be about to obtain a First or Upper Second class UK honours degree, or the equivalent qualifications gained outside the UK, in an appropriate area of science, engineering or technology.
Before you Apply
Applicants must make direct contact with preferred supervisors before applying. It is your responsibility to make arrangements to meet with potential supervisors, prior to submitting a formal online application.
How To Apply
To be considered for this project you MUST submit a formal online application form - full details on eligibility how to apply can be found on the BBSRC DTP website https://www.bmh.manchester.ac.uk/study/research/bbsrc-dtp/
Your application form must be accompanied by a number of supporting documents by the advertised deadlines. Without all the required documents submitted at the time of application, your application will not be processed and we cannot accept responsibility for late or missed deadlines. Incomplete applications will not be considered. If you have any queries regarding making an application please contact our admissions team [Email Address Removed]
Equality, Diversity and Inclusion
Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website https://www.bmh.manchester.ac.uk/study/research/apply/equality-diversity-inclusion/
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