Title: Identifying genetic and cellular determinants of skeletal health and disease.
Abstract: Single-cell molecular QTL studies (molQTL) are increasingly being used in conjunction with data from genome-wide association studies (GWAS) to identify genes involved in human disorders and define the cells in which they function. However, the application of molQTL to GWAS of skeletal traits and disorders is limited by a lack of high-quality molecular data derived from healthy bone tissue. Isolating viable cells from bone is inherently difficult, and the process in which bone tissue is obtained is highly invasive. These technical and ethical challenges render molQTL studies challenging, and alternative approaches are needed. This presentation describes an attempt to address this knowledge gap. Our team conducted single-cell RNA sequencing to define the landscape of cells present in different bone compartments of mice, and then analysed this data with information from human gene-mapping studies of rare and common skeletal disorders, as well as with functional studies of the skeleton in ~1000 mouse lines with single gene deletions. Data generated by our research implicates bone resident cells, as well as endothelial and vascular cell types that have underappreciated roles in skeletal health. Our study also implicates many new genes and describes the different cell types in which they may function to influence pathogenesis of human skeletal disorders.
Biography: Dr John Kemp recently established the Musculoskeletal Genomics Group (MSKG) at Mater Research. Under his guidance, MSKG is developing innovative ways to combine information from statistical and molecular studies to identify biological mechanisms that can be targeted therapeutically to improve skeletal health. Previously, Dr Kemp developed a keen interest in molecular genetics while studying a BSc at the University of Pretoria (South Africa). After completing his Honours Degree, he secured a scholarship from the University of Newcastle Upon Tyne to study a MSc in medical genetics. Dr Kemp was subsequently awarded a Wellcome Trust PhD studentship in molecular genetics and life-course epidemiology from the University of Bristol. He duly completed his PhD, focussing on the genetics of osteoporosis, which is a common and debilitating skeletal disorder. Dr Kemp relocated to Australia and gained extensive experience in statistical genetics while working as a NHMRC research fellow at The University of Queensland. During this time, he published numerous papers on osteoporosis genetics in high impact journals, including Nature Genetics.