Imaging transcription factor DNA target search in a living cell
- Department / Centre
- Biochemistry and Pharmacology
|Dr Elizabeth Hindeemail@example.com|
Summary The Hinde group The research focus of the Hinde lab is on the architectural organisation of the cell nucleus and how chromatin dynamics facilitate navigation of the genome. Inside the nucleus of a living cell, DNA is folded into a multi-layered 3D structure called chromatin. At any moment in time, thousands of proteins are diffusing throughout this structural framework - scanning the genome for a target DNA sequence. The question is “does the chromatin network serve as ‘road map’ for molecular traffic during DNA target search?” To investigate this, we are developing microscopy methods - based on fluorescence lifetime and correlation spectroscopy - to track how proteins move throughout the DNA networks of a living cell. Using this technology we have discovered sub-micron rearrangements in chromatin density that direct the diffusive route of DNA repair factors to damage sites and mediate transcription factor accumulation at specific nuclear locations. This body of work demonstrates an active role for 3D chromatin organisation in nuclear factor navigation. This is important because a hallmark of cancer is genome dysregulation.