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Cis regulatory control of tissue patterning
During development cells specialise in response to signalling cues. To accomplish this, they must turn on and off gene expression programs. Cis-regulatory elements control gene expression with exquisite spatial and temporal precision. We know that they are bound by transcription factors, but it is still not trivial to find them, and we are not able to predict their activity from sequence. The primary goal of our research is to understand how the听non-coding genome听regulates cell fate decisions during development. Our strategy to achieve this is to study the听mechanistic principles听of cis-regulatory elements in development. Long-term, our aim is to predict the functional outcomes of non-coding variation in development and disease. To bridge molecular mechanisms of cis regulation to developmental phenotypic consequences, we combine听in vivo听embryology with听in vitro听cellular models. Our model system is the developing spinal cord, where a small combination of signals directs the specification of neural progenitors and therefore which neurons they will make. We use a variety of novel genomics and computational methods, developing new approaches when needed. Our current projects include state-of-the art proteomics and microscopy approaches to address the mechanistic principles of how cis-regulatory elements control cell fate choice between neural progenitors.
