On the right path in genomics research
EU-funded researchers are shedding new light on the highly complex mechanisms controlling the activity of our genes. The results of the 3-year, EU-funded GENNETEC project ('Genetic networks: emergence and complexity'), which is funded with EUR 1.48 million under the Information society technologies Thematic area of the Sixth Framework Programme (FP6), will help take the potential of genomics a step further with new ways of identifying the regulators controlling specific genes. In organisms ranging from bacteria to human beings, genes are constantly being switched on and off. Genomics is the study of the workings of this complex web of genes and the factors that regulate them. The molecules that switch genes on or off are called transcription factors or genetic regulators and researchers are currently trying to find the mechanisms that operate them. The GENNETEC project set out to identify which transcription factors regulate which genes. Transcription factors bind to particular sites on a chromosome to turn nearby genes on or off. The consequent pattern of gene activity is responsible for a cell or organism's development, function and response to environmental challenges and stimuli. Malfunctions in this system can cause diseases including cancer. 'A disease might sometimes be considered an improper change in the dynamics of a network of interactions,' said Dr François Képès from France's Centre National de la Recherche Scientifique (CNRS) and coordinator of GENNETEC. 'So understanding their properties and how to correct or control their dynamics is essential.' Until recently, researchers had looked for short DNA (deoxyribonucleic acid) sequences that were known to bind to specific regulatory molecules in order to try to match genes with possible transcription factors. But the drawback of this method is that it leads to many potential connections that later prove false. The GENNETEC team undertook a new approach for studying transcription factors. In a previous study they had found that genes which respond to the same transcription factor are often placed at regular intervals along a chromosome. The team suspected that grouping the transcription factors and related genes together helps to optimise their functioning. In order to prove that the locations of these genes help to determine the structure of a particular strand of DNA, the team used numerical simulations of DNA folding. This enabled them to identify gene-transcription factor relationships much more efficiently. 'Combining the two predictors allows us to anticipate the regulators of a particular gene much better by cutting down on the false hits, ' explained Dr Képès. 'We typically double the specificity of the prediction. 'What we discovered is that there is a clear link between chromosome structure and gene expression, a link that we can now predict in a very precise and workable way. We're now in a better position to understand genetic regulation in human cells for a lower cost and in a shorter time.' One of the GENNETEC partners, NorayBio, a biosciences software company based in Spain, is already developing software to allow researchers all over the world to use the same approach to analyse networks of genes. The GENNETEC consortium has also made its own simpler version of the software available free of charge. Dr Képès says the consortium's research on complex genomics systems is as important as the new software, as it can be applied in diverse fields including engineering systems. 'Cells have just one genome, but with that one genome they can cope with multiple challenges,' he commented. 'We can use this biological solution as inspiration to make a new generation of algorithms to address complex problems better than before.'