Apart from the Eiffel tower, the City of Lights boasts a myriad of hidden charms, history and emotion. Before long I find myself face to face with the great Panthéon, burial site of the patron saint of Paris, Geneviève. Also contained within the Corinthian crypt are the ashes of Marie Curie, who discovered radium. A brief stroll takes me to the Curie institute, set up in her name in aid of cancer research. There, at the back of a rose garden, I meet Geneviève Almouzni for coffee.

“I work on how genetics and epigenetics are interconnected.” Geneviève takes an artistic perspective inspired by her old ballet classes.” If you imagine genes as dancers and the cell nucleus as a stage, epigenetics would be the choreography. Then genes might perform Swan Lake in liver cells, the Sleeping Beauty in neural cells and perhaps even The Firebird in muscle cells.” Her group work on neatly choreographed nuclear bundles called nucleosomes, which occur at regular intervals along the length of DNA. Made from histones that are tagged in different ways, they influence genes by what some scientists are now calling a histone code.

 “In any case whether or not there is a code,” says Geneviève, “you need not only duplicate DNA but the way it is arranged, to maintain genome stability.” This is the challenge of the post-genomic era. “Major genome instability is associated with diseases like cancer,” she continues. “The study of histone metabolism may well offer new avenues for diagnostics and therapeutics in cancer.” To date chemotherapy has been the most effective treatment for cancer, but the side-effects are physically and emotionally traumatic. Anti-cancer strategies based on specific biologically active molecules are potential avenues for less severe forms of treatment.

As I wander the winding streets of Montmartre peeking through the windows of ivy-clad houses and artists’ studios, I momentarily forget the nearby siege of coach tours at the Sacré Coeur. Within the rustic confines of a quiet patisserie, Vincent Colot (URGV, Evry) tells me about his work on a variety of cress plant. Vincent is trying to get to the bottom of natural variation. “We want to know what is not caused by genetic polymorphisms but by changes in the epigenetic state of some loci” he explains. Curious, I quiz him on existent examples of natural epigenetic variation. “Let’s start with a beautiful example of an epimutation in a variant plant that Linnaeus isolated in Sweden” he begins. The yellow toadflax grows on the way sides of Europe. Normally flowers are similar in shape to those of a snapdragon. In the 1700s Linnaeus found an unusual natural variant with radially symmetrical flowers. Closer recent inspection has shown this mutant flower to be a result of too much methylation on the Lcyc gene, rather than a mutation in the DNA sequence of the gene. This reversible property of DNA means that mutant toadflax flowers can revert to normal during the life of a plant. Vincent explains that agricultural breeders in France are encouraged to ensure less than 5% variation in the offspring of crop plants. But the reality is that for some crops, aberrant plants arise at rates well in excess of this value for reasons that remain mysterious. One thing, however, is certain. There’s clearly too much natural variation to be explained by genetic mutation alone. “Genetics has been built up on this notion that it’s only DNA sequences that are responsible for heritable changes in phenotype”, he asserts. Vincent believes that some natural variation is likely the result of epimutation as has occurred in wild toadflax. “Somehow the environment may have a long lasting impact, which can be carried through generations”, he adds.