MTZ®-MPI-Award 2017 to Clemens Hug
On December 14th 2017, the MTZ® foundation will present Clemens Hug with the MTZ®-MPI-Award. Since 2009 the MTZ® foundation has honored young scientists at the MPI for Molecular Biomedicine with the yearly MTZ®-MPI-Award, which is endowed with 2,500 Euro. The sponsor couple Monika and Thomas Zimmermann aim to support young people on their journey towards research. Clemens Hug, who is a doctoral student with Dr. Juan M. Vaquerizas at the Max Planck Institute for Molecular Biomedicine, has published a significant article on the 3D organization of the genome in the renowned journal Cell.
Every single cell in our body contains DNA molecules that consist of over 3 billion individual letters. Together they form our genetic material, in which all the information necessary for our development is stored. All DNA molecules in a single cell taken together would give a thread that is about 2 meters long.
"Surprisingly, cells are able to fold and condense the genetic material in their nuclei to a size of only a few microns," says Clemens Hug, a doctoral student with Dr. Juan M. Vaquerizas at the Max Planck Institute for Molecular Biomedicine in Münster. The exact nature of the folding and spatial positioning of the DNA is enormously important, in order to ensure communication between distant parts of the genome. Despite its dense packaging, the genetic material in each cell must still be able to produce messenger RNA for specific proteins and DNA must be ready to be copied before every cell division. When mutations occur that disrupt the spatial organization of the genome, diseases such as cancer can arise.
Recent advances in genomic techniques made it possible to study this 3D organization of the genome in detail. Until now, however, it was unclear when during embryonic development the genome establishes its specific 3D organization. Now, Clemens Hug, using genomic techniques in young embryos of fruit flies, has shown how the 3D organization of the genome first emerges. He published his data in the renowned journal Cell.
One of the basic 3D structures are so-called TADs (topologically associated domains): short sections of the genome that are folded into compact knots resembling balls of yarn.
Until now, it was unclear how and when these compact TAD structures arise. Clemens Hug was able to show that around 1.5 hours after fertilization, at certain locations of the genome, boundaries emerge that form barriers across which contacts between DNA can no longer form. Each subsequent cell division creates additional boundaries. About 2.5 hours after fertilization, these boundary regions are then sufficiently close together so that compact, tangles between adjacent boundaries are formed, the TADs.
At this point, the embryo takes control of its own development for the first time - the influence of maternal gene products decreases. Gradually, the embryo’s own genes are read and transcription takes place for the first time. "We looked at which genes are being read at this moment and which sequences are represented at the TAD border regions. In doing so, we discovered that the boundaries are almost always formed at genes that are constantly being read in all cells, "says Hug. This observation suggests that gene transcription is responsible for the emergence of the border regions. Surprisingly, however, an experiment in which transcription was shut down demonstrated that transcription is not involved in the formation of the 3D structure. "Instead, the reason for establishing the borders probably involves the recruitment of many DNA-binding proteins that bind to the border regions before the start of transcription," says Hug.
"Our discoveries help to understand how the genome manages to activate genes in the right cell at the right time," says Hug. "The 3D structure of the genome plays an important role, because only if the DNA is arranged correctly in the nucleus can regulatory DNA sequences and genes come into contact with each other for gene activation," he continues. An incorrect structure, for example, by loss of a border region or formation of a new TAD in the wrong place, can lead to severe embryonic malformations and development of cancer. Therefore, an accurate understanding of the mechanisms how these 3D structures emerge is very helpful.
About Clemens Hug
Clemens Hug, 29, received his Bachelor of Science in Biological Sciences at the University of Konstanz. He has been awarded an Utrecht Excellence Scholarship for his Master of Science in Molecular and Cellular Life Sciences to Utrecht University in the Netherlands. During this time, he completed two research projects: one at University Medical Center Utrecht and one at Harvard Medical School, Boston (USA). Clemens Hug started his doctoral research work in 2013 with Dr. Juan M. Vaquerizas as part of the International Max Planck Research School, to which only the best candidates are admitted. Clemens Hug has two publications in his name.