EASTBIO: How do fingers grow and can they regenerate at the University of Edinburgh

Supervisors:

Megan Davey, Neil Vargesson, Mike McGrew

Digits- fingers and toes, are segmental structures made up along their length by a series of small bones called phalanges, separated by synovial joints. While the number of digits which form during embryonic development is both highly conserved and a classical model to understand the general mechanisms of embryonic development, how fingers and toes actually grow out and segment is fundamentally unknown. Altered digit development is, however, the most common form of congenital hand or foot differences with important implications for welfare of people and animals. Brachydactyly, for example, in which phalanges are small or malformed is estimated to occur in up to 2% of human live births. Our digits also play an important role in accessing and manipulating our environment, but as most people know, this frequently leads to damage or even loss! A loss of a finger or toe, has profound functional consequences, especially as humans, like many vertebrates, have a very limited ability to regenerate their digits. This project aims, for the first time, to visualise digit outgrowth using ex-ovo imaging of chicken embryos expressing cartilage reporters, combined with computer visions analysis, to answer the question ‘How does a finger grow?’.

Using classical embryology and manipulation techniques in some of the most advanced transgenic chicken embryos ever developed, this project will explore the tissue and genetic interactions of digit outgrowth, potentially to discover an embryonic digit stem cells population. Furthermore, as the anatomy of digits in the animal kingdom is extremely diverse from animals which stand on the tips of their toes, such as horses to whales which can have up to 14 phalanges, research in this exciting area, will generate insights in evolutionary development (Evodevo) as well as contribute to understanding human limb differences and regenerative biology.

This project will leverage a well-established model of embryonic development, the developing chicken embryo, using unique transgenic chicken lines held by the National Avian Research Facility at The Roslin Institute. The project will utilise newly established genome engineering approaches developed by the McGrew lab alongside classical embryology and manipulation, molecular biology approaches including HCR RNA in situ hybridisation, live embryo imaging, confocal, lightsheet microscopy and computer vision analysis.

Funding information and application procedures

• This 4 year PhD project is part of a competition funded by EASTBIO BBSRC Doctoral Training Partnership (DTP) www.eastscotbiodtp.ac.uk/how-apply-0

• EASTBIO Application and Reference Forms can be downloaded via www.eastscotbiodtp.ac.uk/how-apply-0

• Please send your completed EASTBIO Application Form along with a copy of your academic transcripts to [email protected]

• You should also ensure that two references have been send to [email protected]  by the deadline using the EASTBIO Reference Form

This opportunity is open to UK and international students and provides funding covering stipend and UK level tuition fees.  The University of Edinburgh covers the difference between home and international fees meaning that the EASTBIO DTP offers fully-funded studentships to all appointees.  There is a cap on the number of international students the DTP recruits.  It is therefore important for us to know from the outset which fees status category applicants will fall under when applying to our university.

Please refer to UKRI websiteand Annex B of the UKRI Training Grant Terms and Conditionsfor full eligibility criteria.

Closing Date: 16th December 2021