NOMIS scientist Alwin Köhler, scientific director of the Max Perutz Labs Vienna and professor of mechanistic cell biology, has published an article in Nature titled “Phase separation directs ubiquitination of gene-body nucleosomes.” Köhler is also leading the Tardinomis – Decrypting Cryptobiosis in Tardigrades project, which influenced this current work. Says Köhler, “We transferred a critical, serendipitous insight on the behavior of intrinsically disordered proteins in tardigrades to this other experimental system. Without NOMIS this cross-fertilization would not have happened.”
A marvel of complexity, the nucleus is the command center of the cell – harboring information, codes and controlled access. But different from man-made command centers, the nuclear interior looks chaotic to the eye of a scientist. Chromosomes, the carriers of genetic information, float amidst a sea of water, proteins, nucleic acids and other molecules, all engaged in a myriad of simultaneous reactions. These reactions have one major goal: to turn genes on and off at the right time and place. This process is called gene regulation and makes a brain cell look and act different from a muscle cell or a liver cell.
A key question in biology is how this works, put differently, how specific proteins become concentrated on a specific gene to turn it on and off. Scientists, who try to painstakingly dissect such ‘genetic switches’, would wish for a simple device that is easy to understand – a mechanical switch with a button to press. However, nature found a different solution and, surprisingly, the solution is – liquid.
DNA is folded into a material called chromatin, which is mostly composed of DNA wrapped around histone proteins. Enzymes can modify histones and thereby affect chromatin structure, which influences whether a gene is active or not. Reporting in Nature, Alwin Köhler’s team discovered that Bre1, an enzyme that modifies histone proteins with ubiquitin exists in a peculiar material state. Bre1 binds another protein, called Lge1 (Large 1), which displays an unusual behavior when viewed under the microscope: Lge1 forms droplets, which are colliding and coalescing. “Solid structures don’t do that; only liquids can” says Laura Gallego, a first author of the study.
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Scientific director of the Max Perutz Labs Vienna and professor of mechanistic cell biology
Max Perutz Labs Vienna