My research aims to challenge the conceptual framework of cell phenotype: from a single molecular profile, to a range of stable molecular states. In the context of human development, differentiation is most often considered as a cell moving through a linear sequence of well-defined molecular states, such that a single fertilized ovum can produce the full range of tissues in an adult human. While embryogenesis certainly follows a predictable series of cell fate, a purely deterministic model does not allow for a range of molecular states to contribute to the same overall phenotype function. An alternative view is that development occurs as a cell moves through a continuum of cell states, such that a most common path is traversed.
During my PhD I evaluated the range of molecular states that contribute to the functional phenotypes of self-renewal and pluripotency that stem cells display. I published evidence that stem cell phenotype is specified by genes operating in the context of a network, and this network maintains the balance between assuring essential functions of the cell and buffering environmental change or perturbation. As a postdoctoral researcher I aim to extend this work by mapping the most common paths of human development, and the degree of constraint on these paths that are necessary for normal function.
Mason, E.A., Mar, J., Laslett, A., Pera, M., Quackenbush, J., Wolvetang, E., Wells, C. (2014). Gene expression variability as a unifying element of the pluripotency network. Stem Cell Reports. Vol. 3, No. 2, pp 365-77.
Davidson, K.C.*, Mason, E.A.*, Pera, M.F*. (2015). The pluripotent state in mouse and human. Development. 142. pp 3090-3099. *Authors contributed equally to this work.
Hough, S.R., Thornton, M., Mason, E.A., Mar, J.C., Wells, C.A., Pera, M.F. (2014). Single-cell gene expression profiles define self-renewing, pluripotent and lineage primed states of human pluripot