31 August 2009

Next gen power unlocks plant/human genetics research

Researchers at the University of Dundee are embarking on a £1million project to unlock the secrets of a form of gene regulation that appears to play a role in processes as varied as the flowering of plants to why humans develop some cancers.

The grant from the Biotechnology and Biological Sciences Research Council to Dr Gordon Simpson and Professor Geoffrey Barton will kick off a research initiative which is expected to generate a massive amount of sequence data - more than twice as much as arose from the sequencing of the human genome.

The researchers will examine the role played by a string of molecules called the `poly A tail’, which is generated as part of the process when DNA is copied as genes are switched on.

“When genes are switched on, the DNA is copied into a related molecule called RNA,” said Dr Simpson, Principal Investigator in the Division of Plant Sciences, part of the College of Life Sciences at Dundee. “The RNA is cut towards the end of the gene and a string of molecules called the poly A tail added. But the RNA isn’t always cut in the same place at the same gene and so deciding where the poly A tail is to be added can have a big effect on a gene’s function.

“This is quite common as messages copied from half of all human genes appear to stop at different places. Recent work suggests that this is an important part of how genes are controlled in cancer cells. Despite this we know surprisingly little about how the selection of alternative sites for adding poly A tails is controlled.”

Dr Simpson’s interest in poly A tails was sparked by work on plants, examining how their genetic activities influence processes such as flowering.

“It is not only human genes that are controlled in this way. Our group has been studying how plants control the time at which they flower and we discovered that certain flowering regulators work by controlling where a poly A tail will be added.

“We are continuing to work with plants as we aim to better understand how flowering is controlled and because working with plants has certain advantages. But the computational tools developed here will be useful for studying the same form of gene regulation in humans and we are already also collaborating with other researchers in Dundee to translate these discoveries into understanding this process of poly A tail addition in human cells.”

The Dundee researchers will be using a special new technology to help them - Next Generation Sequencing, a recent innovation that will be used to identify the different RNA messages made from genes to find out where they end and to measure changes in which end is chosen.

“This project will generate a lot of data - around twice as much sequence data as in the human genome, requiring the development of new computational tools to reveal the regulation involved,” said Geoffrey Barton, Professor of Bioinformatics in the College of Life Sciences.

“We are only able to do this kind of research because of the massive advances which have been made in sequencing technology in the last two years. More sequence data has been generated world-wide in the last six months than in the past 30 years, so there are huge leaps being made in the ability to carry out this kind of research.

“At Dundee we have the combined expertise to pursue research like this.”

The funding lasts for three years and will create two new post-doctoral jobs in the College of Life Sciences.

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Roddy Isles
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University of Dundee
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E-MAIL: r.isles@dundee.ac.uk