Investigating the role of phase separation in enhancer-dependent gene regulation

Enhancers are regulatory DNA sequences that control when, and in what tissue,
particular genes are turned on and off. The process of gene activation from
enhancers requires a number of factors, including epigenetic enzymes that bind
to enhancer regions in the genome, and non-coding RNAs (eRNAs) transcribed
from enhancers.
Phase separation has recently emerged as one of the most exciting and fast-
moving areas of biology. Phase separated condensates are membraneless
organelles containing high densities of proteins and nucleic acids. They exist in
a separate phase to the surrounding cellular environment, providing a method to
compartmentalize and concentrate biochemical reactions in the nucleus.
Recent evidence has pointed to a role for phase separated condensates as
regulators of highly active enhancers. In this project, we will develop new
methodologies to understand how phase separation affects the activity of
enzymes responsible for enhancer function. You will join a highly collaborative
and dynamic research environment within the Sheffield Institute for Nucleic
Acids, where you will learn cutting edge approaches including next generation
sequencing, RNA biology, real time imaging (single molecule FRET) and
biochemical approaches to study chromatin modifications. The work will provide
a new understanding of one of the most relevant questions in biology and will
have broad ranging outcomes, from understanding human diseases to improving
biotechnology.