2012 Balzan Prize for Epigenetics
The properties of any living organism are determined by its genetic constitution (genotype) and its interaction with the environment during growth and development. Originally it was thought that genetic information solely consisted of the instructions encoded in the organism’s DNA sequence. Over the last 50 years, more and more evidence has accumulated that other information is preserved as cells divide and even from one generation to another. The study of this phenomenon is called epigenetics and just as one can map the genome and identify genetic markers so one can talk about the epigenome and epigenetic markers. Investigation of the molecular basis of epigenetic information is one of the most active areas of current biology. Long DNA molecules in the cell are packaged and organised through the action of proteins called histones. Subtle modifications of histone proteins as well as reversible changes to the DNA itself (the addition or removal of methyl groups) determine whether the genes in local stretches of DNA are active or not (gene expression). These modifications may be temporary or survive through multiple cell divisions. Many researchers have contributed to the mechanistic understanding of epigenetic marking, the work of David Baulcombe being some of the most significant. Baulcombe discovered that small RNA molecules played a critical role in regulating gene expression. Working in plants he first demonstrated that these molecules could turn off genes after their DNA had been translated into RNA but before proteins were produced. This gene silencing is critical in development (cell differentiation and organ formation), but also plays an important role in how plants defend themselves from viruses. There may also be evolutionary implications of his work because some types of epigenetic marks can persist from one generation to the next. Baulcombe has helped unravel the complexities and origins of the different classes of small RNA molecule, and showed how they could determine patterns of epigenetic DNA methylation. Much of what he has discovered is applicable to animals, indicating these are ancient processes that evolved at the base of the evolutionary tree that gave rise to multicellular plants and animals. David Baulcombe’s research has led to enormous progress in our knowledge of plant molecular biology. It also has major implications in biomedical research. Researchers aim to understand why some cells (stem cells) can differentiate into many cell types while most others have a fixed fate. Much of the reason concerns how the DNA is epigenetically marked. Further progress in this field will help us understand the “dedifferentiation” that occurs in certain cancers, how stem cells needed for different therapies can be manufactured, as well as generally increasing knowledge of the fundamental role of small RNA molecules in mammalian development.