New publication

cslteaserAfter about four years in the making, we’ve finally published our paper “A combination of computational and experimental approaches identifies DNA sequence constraints associated with target site binding specificity of the transcription factor CSL” (the title, I know!!!). Please find the PDF here.

This has been an exciting journey. About four years ago I stared at a sequence motif that I got out of motif inference from a CSL/Su(H) ChIP dataset I analysed in collaboration with Sarah Bray’s group. There were a few good reasons to believe it was legit, but Sarah wasn’t convinced at all — not in the light of a crystal structure that Rhett Kovall had published in 2004. The paper discussed why the canonical motif was such a good fit for CSL, but it didn’t offer any entry point for why other sequences might be bound as well. A couple of hours with my favourite crystallographer Ilka Müller convinced me that CSL might prefer it’s canonical motif CGTGGGAA, but she also suggested to me that the space of possible sequences that are “tolerated” by the protein might be significantly larger. I presented these thoughts at a conference that was also attended by Bobby Glen, and we soon decided to team up to tackle the question more systematically using the tools of computational chemistry. Bobby and I proposed this to Apple for an ARTS Award, who presented us with some $30k of hardware, and the rest is history…

In the meantime, Sarah Bray took over the experimental validation of our computational results and because in vivo behaviour often doesn’t tell you much about what the protein really does, the very Rhett Kovall joined forces and provided additional biophysical measurements about CSL/Su(H) binding to DNA.

A truly international and interdisciplinary team. I’m proud of having been a member of it. And well done, Eddie and Rob from my CSBC team.

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