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Click here to search FindAPhD.com for PhD studentship opportunitiesWhat is the interrelationship between cell mitosis and cell polarity during apical-basal polarisation of epithelial organs?
About the Project
My group strives to uncover how mechanics and biochemical signalling work together to shape epithelial organs during development. Our long-term goal is to uncover how a dysregulation of this balance might lead to disease. We recently used a mouse embryonic stem cell culture model of the mammalian epiblast to identify a new Cadherin-mediated mechanism of apical membrane initiation site (AMIS) localisation within developing epithelial cavities. This suggests that cell-cell adhesion acts as the first symmetry-breaking event in de novo polarising epithelial tubes and cavities (Liang et al., 2022). We found that this process occurs even in the absence of cell division. However, it is also accepted in the literature that cell division is sufficient to direct AMIS localisation, via docking of apical proteins at the mitotic midbody (reviewed in Buckley & St Johnston 2022). Other collaborative work within the zebrafish neural tube suggests that this is likely due to the mitosis-dependent alignment of cytokinetic midbodies with Cadherin and apical polarity proteins (Symonds & Buckley et al., 2020). It remains unclear how this alignment occurs or what localises epithelial progenitor cell mitoses at the correct location within developing organs.
This in vivo project within the developing zebrafish neural rod will ask:
1. Is early AMIS formation sufficient to localise neuroepithelial progenitor mitosis localisation? Parallel genetic and optogenetic methods of dysregulating or mislocalising AMIS proteins such as Par-3 will be used, in combination with live confocal imaging of mitosis location.
2. Are actomyosin-mediated cortical flows during cleavage furrowing responsible for aligning AMIS proteins with the midbody? High-resolution Airyscan imaging will investigate the spatial and temporal relationship between AMIS and non-muscle myosin II (NMYII) molecules during mitosis. Optogenetic manipulation within the live zebrafish neural rod (Buckley et al. 2016) will investigate whether NMYII contractility is necessary and/or sufficient to localise AMIS proteins.
Training/techniques to be provided
Zebrafish embryo microinjection, live confocal imaging, optogenetics, molecular biology, image analysis
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The University of Manchester boasts a reputation for pioneering research and innovation, with 25 Nobel Prize winners and more than 20 centres of research excellence. As of 2024, The University of Manchester ranked as the 32nd best university in the world by QS, and the 2nd in the world for social and environmental impact of the THE Impact Rankings. Manchester is a friendly and multicultural city with award-winning museums and world-famous football clubs, and voted the UK’s best city to live in for nine consecutive years.
Entry Requirements
An undergraduate degree in an area relevant to the project (e.g. developmental biology, cell biology, biophysics). A good understanding of cell and developmental biology, including a familiarity with epithelial development and polarity.
Lab research experience is essential, preferably in a related area of research. Experience of image analysis and coding and statistical language would be very advantageous.
How to Apply
For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (https://www.bmh.manchester.ac.uk/study/research/apply/). Informal enquiries may be made directly to the primary supervisor. On the online application form select the PhD Cell Matrix Biology & Regenerative Medicine.
For international students, we also offer a unique 4 year PhD programme that gives you the opportunity to undertake an accredited Teaching Certificate whilst carrying out an independent research project across a range of biological, medical and health sciences. For more information please visit https://www.bmh.manchester.ac.uk/study/research/international/
Equality, Diversity & 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/
Funding Notes
Details of our different fee bands can be found on our website https://www.bmh.manchester.ac.uk/study/research/fees/
References
• Buckley CE & St. Johnston D (2022) Apical-basal polarity and the control of epithelial form and function. Nat Rev Mol Cell Bio https://doi.org/10.1038/s41580-022-00465-y
• Symonds ACE1, Buckley CE1†, Williams C, and Clarke JDW† (2020) Coordinated assembly and release of adhesions builds apical junctional belts during de novo polarisation of an epithelial tube. Development. Dec 147:dev191494. https://pubmed.ncbi.nlm.nih.gov/33361092/
• Buckley CE, Moore RE, Reade A, Goldberg AR, Weiner OD and Clarke JDW. (2016) Reversible Optogenetic Control of Subcellular Protein Localization in a Live Vertebrate Embryo. Dev Cell. Jan 11:36(1): 117-26 https://www.ncbi.nlm.nih.gov/pubmed/26766447
• Buckley CE, Ren X, Ward LC, Girdler GC, Araya C, Green MJ, Clark BS, Link BA and Clarke JDW (2013). Mirror-symmetric microtubule assembly and cell interactions drive lumen formation in the zebrafish neural rod. EMBO J. Jan 9;32(1): 30-44
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3545300/
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