AXA Chair in risk prediction in age-related diseases

For some years now, we’ve known the entire DNA sequence that makes us human. We often hear that a specific gene has been linked to cancer, to Alzheimer’s, to cardiovascular or other age-related diseases. Yet, do we know what all this means for us individually, who will develop these problems, how much risk each of us carries? Not really. Not yet.
Dr. Ben Lehner leads a team that is making progress towards personalized medicine by advancing our understanding of how genetic information is translated into its physical expression in an organism. The delay up to now in this area of research has been due to the sheer complexity of that process: the extremely sensitive interactions among our biological systems, the influence of external factors like environment and life history, and even the role of random events within our cells. Nevertheless, Dr. Lehner has had success addressing each of these aspects.
His team has examined, for example, the variation among individuals’ DNA sequences and asked if the phenotypes that would result—the physical expression of those genes—could be predicted. Through a large-scale experiment on yeast, they found that even simple genetic models were fairly accurate in predicting how these individual cells would differ on a number of traits. The researchers knew that such genetic variation plays an active role throughout development, yet many analyses consider only the characteristics that result at the end. Dr. Lehner went on to develop a method of tracking the influence of genetic variation on development itself—in this case, in the common lab organism, C. elegans. “This approach,” he explains, “could be used to study how genetic variation influences any dynamic process such as human development or disease progression.”
Another angle of his research focuses on the impact of random events affecting our genes. A long-term accumulation of errors in the DNA may not be necessary to trigger the development of cancer; a single mutation in a cell can be all it takes. Indeed, this is a frequent cause of the disease, the researchers discovered. The Lehner team identified precisely how, at the level of our genes, one class of such mutations leads to cancer, and noted that the rate at which mutations occur varies greatly, but predictably, across the entire set of human genes. This, they worked out, is mainly due to differences in the efficiency of the cellular system for DNA repair.
This wealth of knowledge that Dr. Lehner’s team has produced regarding what controls and influences the physical expression of genetic information is poised to offer great insight into the medical reality written in our genes. Such information will participate in the coming revolution aimed at personalizing medical treatment to every individual, for a better targeted, more effective fight against the troubles of aging and disease.