The Roslin Institute
There are two main research themes in my laboratory,
1. Induced pluripotent stem cells (iPSCs) in veterinary biomedicine. iPSCs are obtained by in vitro reprogramming adult differentiated cells into embryo stem-like cells. Through their ability to differentiate virtually into any body tissue, iPSCs have revolutionised human biomedicine by providing an unparalleled platform to model and understand disease in vitro, as well as offering exciting prospects in clinical tissue regeneration. Similar potential, although so far much less explored, exists for iPSCs in veterinary medicine and the improvement of farm animal production. My laboratory has successfully generated iPSCs from horses and cattle and shown for the first time their ability to generate clinically- and production-relevant functional cell types (Breton et al., 2013; Sharma et al., 2014; Cravero et al., 2015). Current studies are aimed at the use of iPSCs in combination with gene editing technologies to 1) understand the molecular mechanisms behind some prevalent musculoskeletal and neural disease in horses 2) elucidate genetic determinants of disease resistance in cattle and 3) develop improved veterinary cell therapies.
2. Biological roles and biomarker potential of microRNAs in animal reproduction. MiRNAs are key global post-transcriptional regulators of tissue growth and differentiation both in health and disease. Because of their stability in body fluids, miRNAs have considerable potential as biomarkers of tissue function and, in fact, miRNAs are already being used as diagnostic biomarkers of human disease. In contrast, the biomarker potential of miRNAs in livestock has not been explored. Previous genome-wide studies in my laboratory identified miRNA populations involved in ovarian follicle growth and differentiation in domestic species (McBride et al., 2012; Schauer et al., 2013; Sontakke et al., 2014). Moreover, by studying both cattle and humans in collaboration with the Edinburgh’s Centre for Reproductive Health, we have recently identified a subset of miRNAs which are critically involved in maintaining the corpus luteum, and therefore pregnancy, in the two species. Current industry-funded work in the laboratory aims to identify relevant miRNAs in circulation that could be used to monitor reproductive efficiency (Ioannidis et al., 2016) and predict life-long health and productivity in livestock.
Breton, A., Sharma, R., Diaz, A. C., Parham, A. G., Graham, A., Neil, C., Whitelaw, C. B., Milne, E. & Donadeu, F. X. 2013. Derivation and Characterization of Induced Pluripotent Stem Cells from Equine Fibroblasts. Stem Cells and Development; 22(4):611-621.
Cravero D, Martignani E, Miretti S, Accornero P, Pauciullo A, Sharma R, Donadeu FX, Baratta M. Generation of induced pluripotent stem cells from bovine epithelial cells and partial redirection toward a mammary phenotype in vitro. Cellular Reprogramming. 2015; 17(3):211-220
Ioannidis J, Donadeu FX. Circulating miRNA signatures of early pregnancy in cattle. BMC Genomics. 2016;17(1):184
McBride, D., Carre, W., Sontakke, S., Hogg, C. O., Law, A. S., Donadeu, F. X. & Clinton, M. 2012. Identification of miRNAs associated with the follicular-luteal transition in the ruminant ovary.
Schauer SN, Sontakke SD, Watson ED, Esteves CL, Donadeu FX. Involvement of miRNAs in equine follicle development. Reproduction. 2013; 146(3):273-282
Sharma R, Livesey MR, Wyllie DJ, Proudfoot C, Whitelaw CB, Hay DC, Donadeu FX. Generation of functional neurons from feeder-free, keratinocyte-derived equine induced pluripotent stem cells. Stem Cells and Development. 2014; 23(13):1524-1534
Sontakke SD, Mohammed BT, McNeilly AS, Donadeu FX. Characterization of microRNAs differentially expressed during bovine follicle development. Reproduction. 2014; 148(3):271-283