Dr T Burdon
,
Dr M Davey
,
Dr D Headon
No more applications being accepted
Competition Funded PhD Project (Students Worldwide)
About the Project
Pluripotent stem cells (PSCs) can be differentiated into most cell types and are readily amenable to precision gene editing, thus enabling functional analysis of genetic variants in culture and affording new opportunities to study the molecular genetics underpinning development, growth and disease. The aim of this project is to investigate the biology of a genetic variant 1 affecting BBS9, a component of the primary cilium BBSome signalling complex, and BMPER, a regulator of the growth factor BMP, in PSCs. Dysregulation of the BBSome in humans results in a number rare diseases (Bardet Biedl Syndromes), characterised by obesity, blindness, polydactyly and kidney failure 2. Bmper mutations in mice are associated with a lethal skeletal disorder. Interestingly, in pigs, a 212 kb deletion that truncates BBS9 and reduces BMPER expression is associated with increased growth rate and feed intake in heterozygotes, but in homozygotes causes embryonic lethality1. The conflicting characteristics of this type of “balancing allele” provide a fascinating opportunity to investigate the biology of genes underpinning functionally important phenotypes relevant to humans and livestock. Moreover, the molecular dissection of the “good” characteristics from the “bad” in PSCs may inform future therapies in humans and instruct novel strategies to improve productivity in livestock. To this end, this project will use CRISPR/Cas9 editing to create BBS9 and BMPER mutations in pig and human PSC lines 3. The genetically modified PSCs and differentiated derivatives, will then be used to assess how the mutations affect cilium structure, cell signalling, BMPER gene expression as well as studying cell growth, differentiation and viability.
Funding Notes
This opportunity is open to UK and international students and provides funding to cover stipend, tuition fees and consumable/travel costs. Applications including a statement of interest and full CV with names and addresses (including email addresses) of two academic referees, should be emailed to [Email Address Removed].
When applying for the studentship please state clearly the project title/s and the supervisor/s in your covering letter.
Other projects available:
We would encourage applicants to list up to three projects of interest (ranked 1st, 2nd and 3rd choice) from those listed with a closing date of 10th January 2021 at https://www.ed.ac.uk/roslin/work-study/postgraduate/studentships
References
1. Derks, M. F. L. et al. Balancing selection on a recessive lethal deletion with pleiotropic effects on two neighboring genes in the porcine genome. PLoS Genet. 14, e1007661 (2018).
2. Jin, H. & Nachury, M. V. The BBSome. Curr. Biol. 19, R472-3 (2009).
3. Gao, X. et al. Establishment of porcine and human expanded potential stem cells. Nat. Cell Biol. 21, 687–699 (2019).
