I am a Presidential Fellow in the School of Medicine, University of Manchester. I am interested in how cells make fate decisions between proliferation and differentiation to generate an organ, in particular the eye. Further I am interested in how changes in cell fate may contribute to developmental ocular disorders. To investigate these questions I use single-cell live imaging together with quantitative analysis of mRNA and protein expression and mathematical modelling.
My live imaging training began during my PhD with Erik Sahai at the Cancer Research UK London Research Institute. Here I used intravital imaging of mice to compare cell signal activation between non-motile and invasive cells during tumour growth and metastasis. This convinced me of the importance of observing gene expression and cell behaviour at the single cell level in vivo and sparked an interest in the dynamic changes in gene expression.
I then moved to the University of Manchester for a post-doc and the post-doctoral fellowship. I worked together with Nancy Papalopulu, James Briscoe at The Francis Crick Institute and Alexander Aulehla at EMBL. My work using quantitative single-cell techniques and live imaging of neural progenitor cells has contributed to the shift towards a more dynamic view of cell fate decisions. I established a method for culture and state-of-the-art live imaging of slices of soft mouse embryonic neural tissue with single cell resolution. I showed for the first time in the developing tissue environment that single cell expression dynamics of the Notch target HES5 are noisy in stem cells and can change over time between random fluctuations and pulsatile oscillatory behaviour. These oscillatory or random fluctuations in HES5 expression correlated with final neuronal sub-type fate.
I now plan to build on this approach to test the role of protein expression dynamics during cell fate decisions in the eye and the role of cell fate in developmental ocular disorders.