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Multi-disciplinary approaches
Multi-disciplinary approaches
Our research concerns the fundamental mechanisms of multi-culluar self-organisation. Research topics span early development of the eyes, nervous system and heart. We use a combination of approaches including in vivo embryology, in vitro pluripotent stem cell culture, and in silico modelling. Model systems studied in the lab include chick embryos, human pluripotent stem cells, and reaction-diffusion systems.
Vertebrate eye development
Vertebrate eye development
The vertebrate eye develops from precisely aligned tissues including the future retina (red), lens (green) and peri-ocular mesenchyme (blue). These tissues develop in a coordinated fashion, controlled by the interactive exchange of molecular signals.
The self-organising retina
The self-organising retina
Why is the Pax6 'master control gene' a potent inducer of eye development? And how can well-developed retinas spontaneously self-organise from pluripotent stem cells?
We identified a Turing network involving Pax6 and two novel eye regulators, Transforming growth factor-beta 2 and Follistatin. Computer simulations of this Retinal Turing Network demonstrate its ability to spontaneously generate 'eye spots' - precursors to the retina.
Genes to geometry
Genes to geometry
The eye develops as a system of three-dimensional tissues. To learn how they take shape we must relate multi-scale regulatory information with the emergent geometry.
We developed software tools that align 3-D imaging data from multiple embryos in order to map molecular, genetic and cellular processes onto the developing anatomy.
Aligning the lens and retina
Aligning the lens and retina
Classical experiments suggested that the optic vesicle (future retina) instructs the lens to develop at the correct time and place, but the molecular nature of that instruction has remained elusive.
More recent work from the Streit lab showed that the optic vesicle's role is more permissive than instructive, because it shelters the future lens from the inhibitory influence of near-by neural crest cells - removing the neural crest cells causes ectopic lens development.
Building on previous work, we were able to determine the nature of this lens inhibition, establishing a molecular mechanism for the alignment of lens and retina.
Controlling a 'master control gene'
Controlling a 'master control gene'
The transcription factor-coding gene Pax6 has been called a 'master control gene' for eye development. Not only is it required for healthy eye development, it is also a potent activator of eye development: inappropriate activation of the Pax6 gene can cause eyes to develop ectopically.
It is therefore important to have a means of inhibiting Pax6 gene activity. We were able to identify one such mechanism - the TGF-beta signalling pathway is able to suppress activity of the Pax6 gene product.
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