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SMI REP

Investigating eukaryotic replisome dynamics at the single molecule level

Total Cost €

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EC-Contrib. €

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Partnership

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 SMI REP project word cloud

Explore the words cloud of the SMI REP project. It provides you a very rough idea of what is the project "SMI REP" about.

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Project "SMI REP" data sheet

The following table provides information about the project.

Coordinator
THE FRANCIS CRICK INSTITUTE LIMITED 

Organization address
address: 1 MIDLAND ROAD
city: LONDON
postcode: NW1 1AT
website: www.crick.ac.uk

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
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 Coordinator Country United Kingdom [UK]
 Project website https://www.crick.ac.uk/research/a-z-researchers/researchers-k-o/nicholas-luscombe/
 Total cost 195˙454 €
 EC max contribution 195˙454 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2014
 Funding Scheme MSCA-IF-EF-ST
 Starting year 2015
 Duration (year-month-day) from 2015-08-01   to  2017-09-30

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    THE FRANCIS CRICK INSTITUTE LIMITED UK (LONDON) coordinator 195˙454.00
2    CANCER RESEARCH UK LBG UK (LONDON) participant 0.00

Map

 Project objective

For cells to reproduce, an accurate duplicate of the genome must be created. This is no small task. The genetic information stored in each cell consists of ~6 billion pairs of nucleobases (base pairs, bp) assembled as a polymer 2 metres long and 2 nanometres in diameter, with the structural form of a double helix. For a mammalian cell to divide, this deoxyribonucleic acid (DNA) must be copied in a time frame on the order of 1 day, or ~70,000bp a second. DNA replication is common to all 3 domains of life, bacteria, archaea and eukarya and is accomplished by a complex of proteins. This proposal brings together a researcher of great proficiency in single molecule methods and multidisciplinary research with the Single Molecule Imaging group at the London Research Institute, one of the world leading centres in DNA replication. Combined, we will build unique instruments and develop single molecule assays to understand the molecular gymnastics of DNA replication in eukaryotes. We will elucidate rates of DNA unwinding by eukaryotic helicases and establish enhancements by association with other proteins. We will also study replisome dynamics by observing synthesis of DNA on custom templates in real time. This will allow detection of replication loops and stalling that may occur. We will also examine the mechanism of lesion bypass. The insight gained is impossible with classical biochemical techniques, as individual replisomes are observed in real time rather than measuring an average of a population. Our methods will reveal heterogeneities and obtain precise quantitative details of the dynamics. Features such as pauses and back slips will enable the study of intermediate states and conformational changes linked to replisome dynamics. This proposal will satisfy academic curiosity of understanding life at the most fundamental level but will also increase our knowledge of the how the cell works and thus becomes the building blocks for disease treatment and cures of the future.

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