Name: Charlie Laughton
Institution: University of Nottingham
Research: Finding new messages hidden in the genetic code with the NGS
A typical human cell is about one hundredth of a millimetre in diameter, yet it contains about three metres of DNA. The DNA in our cells is incredibly tightly packed but in a way that still allows the genetic code to be read so the cells can survive, grow and divide. At the moment there is no clear understanding of how this works, but one thing that is known is that the shape and flexibility of DNA, and how it can be bent and twisted, varies along its length in a way that's related to this same genetic code.
In Charlie’s research he used computer simulations to try and break this code but even the most powerful computers are not good enough to enable the study of the entire DNA in a cell at once. Charlie divided up the DNA into small sections, studied the flexibility of these sections by a simulation method called molecular dynamics (MD), and then put the results for all the fragments back together again.
This isn’t being done just out of pure scientific curiosity – understanding why some bits of DNA are flexible and some are stiff, why some bend one way and some another, helps us understand how cells use these properties to switch genes on and off, and how we can then influence this in new ways. Ultimately it may help to find new drugs to treat diseases such as cancer, develop new biofuels, and crops that can resist climate change.
In a recent project Charlie used the computing power provided by the Leeds node of the NGS to create a sort of ‘production line’ so that molecular dynamic (MD) simulations of many different fragments of DNA could be undertaken and analysed in a highly automated manner. The MD simulations themselves were performed using the AMBER package installed on the NGS, while the programs to prepare the DNA fragments for simulation, control the ‘production line’, and analyse the results were written by his research team. The NGS systems are basically just much larger versions of the same machines in his own lab, so Charlie and his project assistant, Hui Wen Ng, were able to develop and install this software very easily without needing any assistance from NGS support.
MD simulations require considerable computer power – to study one of these fragments on a typical workstation would have taken about two weeks of CPU time. Using the power of the NGS this could be reduced to about 24 hours, and so the study that Charlie undertook – which involved an analysis of nearly one hundred different DNA fragments – was completed in about three months instead of two years.
Charlie said “We undertook this project as part of the Ascona B-DNA Consortium - a large multi-national collaboration involving scientists from across Europe and the US; without the compute power and high-throughput provided by the NGS, we would not have been able to deliver our part of the project in a timely manner. At a more personal level, it led to one of the most highly cited publications* I have ever had.”
*Perez, A; Marchan, I; Svozil, D; Sponer J; Cheatham III TE; Laughton CA; Orozco M. (2007) Refinement of the AMBER force field for nucleic acids: improving the description of alpha/gamma conformers. Biophys. J. 92 3817-3829.
PI - Dr. Charlie Laughton
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