Dr Cerys Manning, Prof G Black
No more applications being accepted
Competition Funded PhD Project (Students Worldwide)
About the Project
Inherited developmental disorders account for much of childhood visual impairment, yet knowledge of their molecular and cellular causes is far from complete. During early eye development stem cells must balance fate decisions between proliferation and differentiation at the same time as undergoing cell migration and morphogenesis to prevent such disorders. Cell fate decisions are controlled by intrinsic factors, such as the gene network and extrinsic factors, such as mechanical signals from the surrounding tissue and extracellular matrix. Mechanical signals are crucial during eye development as mutations in the mechano-transducer YAP lead to coloboma in humans, a rare developmental disorder arising from failure in optic cup folding and fusion. Critically, the co-occurrence in many patients of coloboma, a structural disorder, and microphthalmia, a cell fate disorder, suggests a mechanistic link between the mechanical environment and cell fate in the developing eye. The hypothesis is that mutations that primarily lead to morphogenetic complications (i.e coloboma), then feedback to affect cell fate, resulting in co-occurrence of coloboma and microphthalmia. This project will involve introducing mutations from clinical reports into humanESCs and mouseES to set-up an in vitro model of coloboma/microphthalmia in retinal differentiation and optic cup organoid protocols. This will subsequently be used to explore the mechanisms of these disorders and the control of cell fate decisions in the eye. These findings will advance understanding of the aetiology of developmental ocular disorders and will be more broadly applicable to the development and regeneration of other tissues.
Generation of three-dimensional retinal tissue with functional photoreceptors from human iPSCs. Zhong, X et al. (2014) Nature Communications.
New variant and expression studies provide further insight into the genotype-phenotype correlation in YAP1-related developmental eye disorders. Holt R et al. (2017) Scientific Reports.
Entry Requirements:
Applicants must have obtained, or be about to obtain, at least an upper second class honours degree (or equivalent) in a relevant subject.
UK applicants interested in this project should make direct contact with the Primary Supervisor to arrange to discuss the project further as soon as possible. International applicants (including EU nationals) must ensure they meet the academic eligibility criteria (including English Language) as outlined before contacting potential supervisors to express an interest in their project. Eligibility can be checked via the University Country Specific information page (https://www.manchester.ac.uk/study/international/country-specific-information/).
If your country is not listed you must contact the Doctoral Academy Admissions Team providing a detailed CV (to include academic qualifications – stating degree classification(s) and dates awarded) and relevant transcripts.
Following the review of your qualifications and with support from potential supervisor(s), you will be informed whether you can submit a formal online application.
To be considered for this project you MUST submit a formal online application form - full details on how to apply can be found on the MRC Doctoral Training Partnership (DTP) website www.manchester.ac.uk/mrcdtpstudentships
Funding Notes
Funding will cover UK tuition fees/stipend only. The University of Manchester aims to support the most outstanding applicants from outside the UK. We 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.
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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