This project is no longer listed on FindAPhD.com and may not be available.
Click here to search FindAPhD.com for PhD studentship opportunities(BBSRC DTP) Does cell shape direct polarisation and force propagation within the developing zebrafish neural tube?
About the Project
The Buckley group strives to uncover how mechanics and biochemical signalling work together to shape epithelial organs during development. We are currently particularly interested in understanding the links between apical-basal cell polarity, cell-cell adhesion, and cellular mechanics during the process of vertebrate secondary neurulation.
Reversible transitions between more fluid mesenchymal and more solid epithelial cell states (EMT and MET) are widespread processes during both development and disease of epithelial organs and have been studied extensively in single cells undergoing migratory EMT (e.g. during neural crest delamination). These exhibit a decrease in adhesion between cells and an increase in protrusive and migratory behaviour as they move from epithelial to mesenchymal states. However, the shape changes associated with cells as they collectively epithelise within solid tissue is less well understood. For example, it is not known how early Cadherin protein upregulation, which we recently demonstrated to be necessary and sufficient for the localisation of the apical membrane initiation site (AMIS) localisation (Liang et al., 2022), is itself upregulated at the middle of organ primordia (Symonds and Buckley et al., 2020). It is also not clear what affect these intermediate cell states have on the mechanical properties of the tissue during morphogenesis.
This in vivo project within the developing zebrafish solid neural rod aims to test:
1. How does the shape of neuroepithelial progenitor cells change over the course of their epithelialisation? Live confocal imaging and machine learning will be used to segment the shapes of individual neuroepithelial progenitor cells and extract parameters such as sphericity, length, volume, apical area and number of cell-cell contacts along their lengths. This will be used to construct maps of cell shape, cell connectivity and nuclear packing over space and time.
2. Does cell shape plays a role in determining the location of the AMIS in the middle of the organ primordium? Cell segmentation will be overlaid with signals from Par-3 and N-Cadherin puncta, to determine whether AMIS localisation is initiated at areas of the cell cortex with the most cell-cell contacts.
3. Does cell shape plays a role in directing force propagation between cells during morphogenesis? In vivo optogenetic manipulation (Buckley et al., 2016) of local tissue stress will be carried out in different spatiotemporal space, alongside particle image velocimetry. This will determine whether force propagation direction and amplitude are affected by local differences in cell shape and connectivity.
Relevant links
https://www.pdn.cam.ac.uk/directory/clare-buckley
https://research.manchester.ac.uk/en/persons/shane.herbert
https://research.manchester.ac.uk/en/persons/raman.das
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/funded-programmes/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/
Funding Notes
References
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/
Search suggestions
Based on your current searches we recommend the following search filters.
Check out our other PhDs in Manchester, United Kingdom
Start a New search with our database of over 4,000 PhDs
PhD suggestions
Based on your current search criteria we thought you might be interested in these.
Developing “intelligent” information technologies using neural markers of multisensory decision-making and learning
University of Leeds
Understanding how to target the T cell compartment within related brain tumours
The University of Manchester
Mapping CD4+ T cell fate decisions and functional coordination within tissues during infection
The University of Manchester
Continue with Facebook