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Details of Grant 

EPSRC Reference: EP/D053102/1
Title: A multi-scale model of charge transport through melted, stretched and in vacuo DNA structures
Principal Investigator: Harris, Dr S
Other Investigators:
Researcher Co-Investigators:
Project Partners:
Department: Physics and Astronomy
Organisation: University of Leeds
Scheme: First Grant Scheme Pre-FEC
Starts: 01 January 2007 Ends: 31 December 2008 Value (£): 125,497
EPSRC Research Topic Classifications:
Biophysics Chemical Biology
EPSRC Industrial Sector Classifications:
No relevance to Underpinning Sectors
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Panel History:  
Summary on Grant Application Form
The DNA double helix carries the genetic information necessary for life using a simple chemical code. However, DNA is under continuous attack from toxins generated naturally by the cell. If the DNA is chemically damaged, then errors can be made when the genetic message is read or copied leading to serious diseases such as cancer. Biology has a number of clever methods both for protecting DNA and for detecting and repairing damage when it occurs, but these remain poorly understood.Recently, experimentalists have devised new ways to introduce damage into DNA under controlled conditions so that they can study the process. They have observed that certain types of damage can cause a positive charge to hop along the DNA until it chemically changes a vulnerable site. However, charge transport does not occur if the regular molecular structure of the DNA is interrupted in any way since this impedes the hopping process. These observations have far reaching implications for how and where genetic damage occurs. In the cell, the DNA is either tightly packaged in the nucleus, or is frequently being manipulated by DNA processing machines which are strong enough to distort the double helical structure. Consequently, it is important to understand how charge transport and damage migration are affected by changes to the regular molecular structure of DNA. This theoretical study will use a combination of physics and computer simulation to produce a mathematical model explaining how charge hops along DNA. We can then use this model to understand why hopping is prevented by particular distortions to its double helical structure. Computer simulations are an extremely powerful tool for understanding complex biological molecules. They can provide information about the molecular structure of the DNA at an atomic level so that the molecule can be investigated in far more detail than would be possible experimentally. This study will use computer modelling to simulate how the structure of the DNA is distorted when it is placed under stress in a variety of ways. Using this information, we can use our mathematical model of damage hopping to calculate whether charge transport will still occur through these deformed DNA structures. This model will provide new insight into existing experiments and suggest future studies to show how the DNA is protected from damage in the cell.
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Organisation Website: http://www.leeds.ac.uk