The marks that mold us
The genetic code is not everything: Heinrich Leonhardt, Professor of Human Biology at LMU, is currently dissecting the epigenetic mechanisms that determine which genes are activated or repressed in each of the diverse cell types that make up multicellular organisms.
Source: Jan Greune
Self-doubt was not on the agenda on 26 June 2000. At press conferences held in cities around the globe, molecular biologists celebrated a collective achievement, acclaimed by many as one of mankind’s greatest accomplishments, comparable to splitting the atom or landing on the Moon. The leaders of the publicly funded Human Genome Project announced that they had deciphered the sequence of the human genome. The data were incomplete and riddled with errors, but 85% of the genome had been successfully assembled. But the decision to reveal this preliminary result was precipitated by the protagonists of the rival project, led by Craig Venter and carried out by his company Celera, who gave a similar press conference on their sequence data at the same time. Three years later a much more accurate and virtually complete version was published, revealing that the 3 billion base-pairs in the human genome encoded some 25,000 genes. In the succeeding decade, however, it has become clear that even this sequence does not provide the answers to many crucial questions.
Why for example do nerve cells differ from skin cells or muscle cells, given that essentially all cells in the body harbor the same genomic DNA sequence? How do their divergent forms and functions arise? Why do identical (monozygotic) twins often differ from one another more than one might expect, although both carry the same genome? Why are they not perfect Doppelgänger? Heinrich Leonhardt has what sounds like a simple answer: Not all genes in the genome are active in all cells, and cell differentiation relies on a network of interactions, a distinctive epigenetic level of control that determines which genes are activated and which are repressed in each specific cell type. As Professor of Human Biology and BioImaging at LMU, Leonhardt studies the exceedingly complex mechanisms that underlie this epigenetic program, which plays a central role in development.
"Nature vs. Nurture"
The epigenetic code is itself a highly dynamic system, Leonhardt explains. It is not a rigid blueprint like the genetic code, which specifies how the nucleotide sequences that make up the genes are translated into the amino-acid sequences of proteins. For instance, it can mediate the transient repression of a gene or set of genes for periods of hours or days not – as was once naively thought – permanently. This of course raises the next question: How are such modifications regulated? The organism basically reacts to every stimulus from its internal or external environment that alters its physiological state, and thus activates signaling networks that orchestrate an appropriate response. Researchers now know that nutritional factors have long-term effects on this control system, as does physical or cognitive activity, air pollution or drug consumption. Epigenetic changes are involved in the pathogenesis of many disorders, in diabetes and depression, cancer and cardiovascular disease. Biologist Rudolf Jaenisch (Massachusetts Institute of Technology) calls them “the language the genome uses to communicate with the environment”.
Genes and Environment have generally been understood as opposing forces, as in “Nature vs. Nurture”. They were the banners raised in ideological battles over the issue of which factor exercised the greater influence on the individual’s personal development, one’s genetic heritage or one’s environment. Leonhardt may have mild reservations about the wording of Jaenisch’s remark regarding epigenetic communication with the environment, but he is in no doubt about the significance of the dynamically responsive interface between genome and environment for the organism, its development and its metabolism: “All roads lead onto the epigenetic plane,” he says. If one wants to understand how humans function, how the individual organism develops and operates, how it reacts at the biological level to its environment, what makes it vulnerable to particular diseases and why, it is essential to understand how the logic elements that make up epigenetic circuits work. This is where Version 2.0 of the human genetic system begins.
The complete article on Professor Leonhardt’s research will appear in the upcoming issue of insightLMU, LMU’s international newsletter.
Prof. Dr. Heinrich Leonhardt
Chair of Human Biology and BioImaging at LMU since 2012. Born in 1961, Leonhardt earned his doctorate in Biochemistry at the Free University in Berlin. After a stint as a Postdoctoral Fellow at Harvard Medical School in Boston, he went on to lead research groups at the Franz Volhard Clinic and the Max Delbrück Center in Berlin-Buch, before being appointed to a professorship at LMU in 2002.