Can using synthetic approaches to build biology help teach us the design principles of how embryos build themselves? 👷‍♀️🔧

If this is a question that interests you, come and share your thoughts at this Royal Society Workshop on Generative Biology

royalsociety.org/science-even...

It was a lot of fun to speak at YEN this week @yen-network.bsky.social. It is such an honour to be awarded the Sammy Lee Medal for my work on engineering CREs

Would not have been possible without the support from the Briscoe Lab — especially @joadelas.bsky.social @dbenzinger.bsky.social — and the broader @crick.ac.uk community

Successfully defended my thesis on predictable engineering of CREs yesterday. An end of an era.

Thank you @jamesbriscoe.bsky.social. And my examiners @wbickmor.bsky.social @kabirhusain.bsky.social

Can using synthetic approaches to build biology help teach us the design principles of how embryos build themselves? 👷‍♀️🔧

If this is a question that interests you, come and share your thoughts at this Royal Society Workshop on Generative Biology

www.royalsoc.ac.uk/science-even...

We use these full-length synCREs to rewire the neural GRN, changing the pattern of motor neuron differentiation in neural tube organoids
9/11

Are modular and pairwise contributions enough? Extrapolating these rules, we predictably re-engineer a full length CRE critical for motor neuron differentiation, building natural-sized CREs that display both boosted and diminished signal-dependent activity, just by shuffling blocks of sequence
8/11

For example, relative fragment spacing in a synCRE changes syntax contributions. This predicts how to convert a signal-independent synCRE to a signal-dependent one by changing only the order of fragments.
7/11

As NeMECiS explores every combination, ordering and repetition of fragments, we used interpretable linear modelling to isolate how pairwise interactions and syntax tune activity
6/11

We discover a simple rule to explain Hedgehog-responsive synCRE activity: the parts have independent modular contributions that multiply to make the whole
5/11

While 200bp fragments show minimal activity on their own, they can combine to make thousands of Hedgehog-responsive synCREs
4/11

We developed NeMECiS, a high-throughput combinatorial cloning and screening strategy. This allowed us to generate synCREs by exhaustively concatenating fragments of neural CREs that respond to Shh
3/11

CREs respond to signalling cues to direct gene expression: can we learn how they integrate information and use this knowledge for predictable engineering of synthetic CREs?
2/11