The field of regenerative medicine was stunned in 2007 by the possibility of creating stem cells from adult human cells (1). Since then it has been shown that it is also possible to trans-differentiate from one mature human cell type to another. The process however is still poorly understood, and as a result, only a handful of different human cell types have successfully been created in the decade following the 2007 discovery (by Yamanaka).
We apply computational approaches to the predominantly experimental field of cell differentiation that bring a systematic and data-driven guide for directing research in the field (2). We combine theory of transcriptional regulation and cell networks with big data from high-throughput experiments relating to gene expression and molecular interaction. As well as expanding the repertoire of possible human cell conversions and pushing the boundaries of cellular manipulation, the PhD project will aim to deepen the understanding of cell fate and evolution (3).
The project would suit highly motivated individuals coming from a range of scientific disciplines, but an aptitude for theoretical and technical thinking will be essential for developing computational skills required to carry out the research.
1) Takahashi, K., Tanabe, K., Ohnuki, M., Narita, M., Ichisaka, T., Tomoda, K. and Yamanaka, S. (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell, 5, 861-872.
2) Rackham, O.J.L., Firas, J., Fang, H.,Oates, M.E., Holmes, M.L., Knaupp, A.S., The FANTOM Consortium, Suzuki, H.,Nefzger, C.M., Daub, C.O., Shin, J.W., Petretto, E.P., Forrest, A.R.R., Hayashizaki, Y., Polo, J.M. and Gough, J. (2016) A predictive computational framework for direct reprogramming between human cell types. Nature Genetics, 331-335.
3) Sardar, A.J., Oates, M.E., Fang, H., Forrest, A.R.R., Kawaji, H., The FANTOM consortium, Gough, J. and Rackham, O. (2014) The Evolution of Human Cells in Terms of Protein Innovation. Mol. biol. evol., 31(6), 1364-74.