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Details of Grant 

EPSRC Reference: EP/T002794/1
Title: TRANSCRIPTION AND NUCLEAR PHASE TRANSITIONS
Principal Investigator: Hebenstreit, Dr D
Other Investigators:
Kantsler, Dr V Ball, Professor RC Dyson, Dr L
Researcher Co-Investigators:
Project Partners:
Department: School of Life Sciences
Organisation: University of Warwick
Scheme: Standard Research
Starts: 01 April 2019 Ends: 31 March 2022 Value (£): 1,747,030
EPSRC Research Topic Classifications:
Biophysics Chemical Biology
EPSRC Industrial Sector Classifications:
No relevance to Underpinning Sectors
Related Grants:
Panel History:
Panel DatePanel NameOutcome
19 Mar 2019 Building Collaboration at the Physics of Life Interface Announced
Summary on Grant Application Form
This project aims at connecting via an interdisciplinary approach two phenomena that are of fundamental importance in biology and medicine.

The first one is transcription, the production of messenger-RNAs (mRNAs) from genes on the DNA. mRNAs are used by cells to make proteins, the main components for function and growth of cells. Understanding function and regulation of transcription is therefore of critical importance for comprehensive insights into cellular function in health and disease. Yet, many aspects of transcription remain unclear and are challenging to study due to the contributions of the second phenomenon we want to study, the dynamical turnover of a certain type of 'clusters' in the nucleus of a cell.

This clustering appears to involve various different proteins, many of which are implicated in transcriptional regulation, and possibly includes DNA and mRNA. This phenomenon was discovered only recently and appears to relate to the regulation of transcription, although mechanistic details are elusive. Apart from its role in transcription, clustering of proteins is a hallmark of neurogenerative diseases, which mandates a better understanding of its functional purposes.

While research in transcription is a biological venture, studying clustering requires a physics approach; the clusters form relatively large structures in the nuclei, which are akin to phase changes that are seen when a liquid substance becomes solid or vice versa. This results in unique biophysical properties within the clusters that are not amenable to biology-based research strategies.

Our goal in this project is to form an interdisciplinary team of physicists, biologists, and mathematicians to investigate the nature of the interactions between clusters and transcription. This provides a chance to explain and unify these two phenomena in a mechanistic sense, along with prospects to include and thus understand many other unexplained biological observations. The biological side of our team will provide expertise and methodology for investigating transcription and its dynamics and for locating important proteins on and alongside DNA and mRNAs. The physicists will investigate the properties of the clusters and their interactions with other objects in the cells' nuclei using advanced microscopic imaging techniques and modelling approaches, with input from mathematicians. The different strands of work in the project will be very strongly integrated to maximize the interdisciplinary exchange and facilitate the emergence of novel insights.

The project will significantly advance our understanding of fundamental processes in human biology, with the associated strong medical implications. It will also contribute to the creation of long-term collaborative arrangements between researchers in different disciplines.

Key Findings
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Further Information:  
Organisation Website: http://www.warwick.ac.uk