Genome organization and gene regulation; microfluidics for cell biology.
One current focus is on validating our model for all genomes. This is based on two heterodox concepts: (i) active polymerases are locally concentrated in discrete sites called ‘transcription factories’, and (ii) these molecular machines are immobilized when active. Then, factories are both active sites of transcription and major organizers of the chromatin fibre.
We imagine a promoter out in a loop initiates by binding to a factory containing the appropriate machinery, and that the frequency of initiation is determined by how closely that promoter is tethered to an appropriate factory. Then, regulatory motifs like enhancers (and silencers) act by tethering their target promoters close to (or distant from) suitable factories rich in appropriate polymerases/factors. [See YouTube movie.]
We are also developing simple ways of doing microfluidics – 'Freestyle Fluidics' for flowing applications, and 'GRIDs' (analogs of microtiter plates) for static ones. We hope these will transform the way small volumes are handled in cell biology.
Trends Genet. 91: 483-490.
Nat. Commun. 8: 816.
Proc. Natl. Acad. Sci. USA 115: E5926-E5933.