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Single-Molecule And Structural Studies Of ATP-Dependent Chromatin Remodelling

Single-Molecule And Structural Studies Of ATP-Dependent Chromatin Remodelling

Objective

The packaging of genetic information into chromatin regulates a wide range of vital processes that depend on direct access to the DNA template. Many chromatin-interacting complexes impact chromatin structure and their aberrant regulation or dysfunction has been implicated in various cancers and severe developmental disorders. A better understanding of the roles of chromatin-interacting complexes in such disease states requires a detailed mechanistic study. Many chromatin-interacting complexes modify chromatin structure, yet understanding the underlying mechanisms remains a major challenge in the field. Furthermore, how chromatin-interacting complexes are regulated to enable their various functions is incompletely understood. We will address these longstanding questions in two specific aims. Aim I: Building on our expertise in single-molecule biology, we will develop powerful single-molecule imaging approaches to monitor the action of chromatin-interacting complexes in real time. We will further probe how the diverse activities of the chromatin-associated complexes are coordinated and coupled to conformational transitions. Aim II: Drawing on our expertise in structural biology, we will use a range of structural techniques in combination with biochemical approaches to study the vital regulation of chromatin-interacting complexes by their regulatory subunits as well as by chromatin features. We expect to obtain ground-breaking insights into the mechanisms and regulation of disease-related chromatin-associated complexes, which may open up new horizons for developing therapeutic intervention strategies. Furthermore, the approaches developed here will enable the investigation of a large number of chromatin-related processes.

Host institution

UPPSALA UNIVERSITET

Address

Von Kraemers Alle 4
751 05 Uppsala

Sweden

Activity type

Higher or Secondary Education Establishments

EU Contribution

€ 1 498 954

Beneficiaries (1)

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UPPSALA UNIVERSITET

Sweden

EU Contribution

€ 1 498 954

Project information

Grant agreement ID: 714068

Status

Ongoing project

  • Start date

    1 March 2017

  • End date

    28 February 2022

Funded under:

H2020-EU.1.1.

  • Overall budget:

    € 1 498 954

  • EU contribution

    € 1 498 954

Hosted by:

UPPSALA UNIVERSITET

Sweden