Elizabeth Hinde - Quantitative imaging of nuclear architecture and DNA target search in a living cell

Inside the nucleus at any given moment in time, thousands of molecules are diffusing throughout 3D genome organisation searching for a target DNA sequence. DNA repair machines look for sites of damage to prevent genetic mutations, and transcription factors undergo site specific DNA binding to maintain normal gene expression. The question is to what extent does nuclear architecture guide the diffusive route of molecules to a target destination? In recent work we developed a series of new fluorescence microscopy methods to track the movement of molecules around the complex DNA networks within the nuclei of live cells. Based on fluorescence lifetime and fluctuation spectroscopy, this technology has the spatiotemporal resolution to map the impact genome organisation has on nuclear traffic. From using these methods, we have discovered that DNA networks rearrange to create highways that facilitate repair and transcription factor recruitment to target DNA sites. This has given us an opportunity to start understanding the biophysical rules for traversing the nuclear landscape.

Hinde et al. 2016. Nat Commun 7, 11047, doi:10.1038/ncomms11047.

Lou et al. 2019. PNAS, published ahead of print, doi: 10.1073/pnas.1814965116