Reprogramming of skin to cornea - new models, methodologies and mechanisms (Durham)
One of the most interesting paradigms in experimental adult tissue reprogramming can be seen with epithelial transdifferentiation. In one example epithelial cells of the eye cornea can be turned into skin and hair, through direct interaction with mesenchymal cells/tissues. From a translational point of view, however, a more pressing requirement is the creation of new cornea stem cells, to replace those lost through injury or disease. Moreover more needs to be known about the underlying cellular and molecular mechanisms, and the epigenetic changes involved in such epithelial transformations. In collaboration with Prof Linda Lako at Newcastle University, we have developed a prototype bilayered three dimensional spheroid culture model of the cornea. This can be further developed for studying cornea biology and function and as a screening platform, but it can also be adapted to test whether skin epithelial cells can be turned in corneal epithelium through direct cell-cell interactions. In this project the aim is to exploit the complementary expertise of the Jahoda and Lako labs and direct skin and hair follicle epithelial cells to become cornea epithelium through a combination of approaches. These will include molecular manipulation of the transcription factor Pax6 and the Wnt signalling pathway, and through direct epithelial-mesenchymal interactions, using our 3D model. Epigenetic regulators play crucial roles in the execution of lineage-specific gene expression programs in skin keratinocytes and the project will investigate changes to DNA/histone-modifying enzymes, and Polycomb genes during cornea to skin and (when successful) skin to cornea transdifferentiation. Outcomes will be both translational and in advancing the underpinning biology. The project will provide training for the student in a wide range of techniques, and allow for significant and exciting interactions with collaborators in the UK and Europe.
For further information see the website: https://www.dur.ac.uk/biosciences/
Please submit a full CV and covering letter directly to [email protected]
This is a 4 year BBSRC studentship under the Newcastle-Liverpool-Durham DTP. The successful applicant will receive research costs, tuition fees and stipend (£14,057 for 2015-16). The PhD will start in September 2016. Applicants should have, or be expecting to receive, a 2.1 Hons degree (or equivalent) in a relevant subject. EU candidates must have been resident in the UK for 3 years in order to receive full support. There are 2 stages to the application process.
Microenvironmental reprogramming by three-dimensional culture enables dermal papilla cells to induce de novo human hair-follicle growth.Higgins CA, Chen JC, Cerise JE, Jahoda CA, Christiano AM. Proc Natl Acad Sci U S A. 2013;110(49):19679-88.