In both humans and domesticated animals, skeletal dysplasias are a source of morbidity. Although rare in humans, skeletal dysplasias are common among most species of domesticated animals. Therefore understanding the genetic mechanisms of skeletogenesis is critical for both One Health and food production. By defining the genetic variants and gene products that alter skeletogenesis, we will empower the development of new therapeutics to improve bone health, enhance genetic counselling of parents/breeders who are weighing the risks of transmitting skeletal defects to their offspring, and potentially guide genome-editing of livestock species to improve skeletal qualities (e.g. long bone fragility in layer chickens).
Due to their extreme phenotypic diversities1-3, dogs are arguably the best mammals for studying the genetic mechanisms of skeletal diversity. In the last two years, the Schoenebeck group and its collaborators have collected over 400 dog skull scans via computed tomography (CT). In parallel, each scanned patient (dog) was genotyped using SNP arrays. This rich body of both phenotypic and genotypic data provides the means to parse the genetic influences of genetic variants on skull size, form, and morphology.
Under the supervision of Drs. Schoenebeck and Farquharson, our PhD student will select a morphological trait from our skull dataset, perform GWAS studies, and conduct QTL mapping and whole genome sequence analysis to identify putatively causal genetic variants that drive phenotypic differences between dog skeletons. In the second half of the PhD, the student will take their discoveries to the wet bench for functional analysis. Here the student will use in vitro methods to determine the effects of gene (or variant) function on osteogenesis. Through application of morphometric, genomic, and cell biology techniques, our PhD will leave the Roslin Institute with a diverse knowledge base that will prepare him/her for a future vocation in a science-related discipline.
Applications including a statement of interest and full CV with names and addresses (including email addresses) of two academic referees, should be sent to: Liz Archibald, The Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, EH25 9RG or emailed to [email protected]
When applying for the studentship please state clearly the title of the studentship and the supervisor/s in your covering letter.
All applicants should also apply through the University’s on-line application system for September 2016 entry via http://www.ed.ac.uk/studying/postgraduate/degrees/index.php?r=site/view&id=830
International students should also apply for an Edinburgh Global Research Studentship (http://www.ed.ac.uk/schools-departments/student-funding/postgraduate/international/global/research).
ALL APPLICATION PROCEDURES MUST BE COMPLETED BY THE CLOSING DATE 1st FEBRUARY 2016
Schoenebeck, J. J. & Ostrander, E. A. Insights into morphology and disease from the dog genome project. Annu. Rev. Cell Dev. Biol. 30, 535–560 (2014).
Rimbault, M. et al. Derived variants at six genes explain nearly half of size reduction in dog breeds. Genome Research 23, 1985–1995 (2013).
Schoenebeck, J. J. et al. Variation of BMP3 Contributes to Dog Breed Skull Diversity. PLoS Genet 8, e1002849 (2012).