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Scientists at TU Dortmund University have achieved an important advance in the field of chemical epigenetics: In two studies, they describe for the first time how light can be used to directly switch the writing and erasure of DNA methylation. A central process in human biology, DNA methylation regulates, for example, the development of embryos and the onset of cancer. The research results have been published in two renowned scientific journals.
To understand what the researchers have achieved, one must first recall the basic biological principles: DNA methylation is a chemical modification of the basic building blocks of DNA – the hereditary substance of a cell. Through this modification, a cell can flexibly switch its genes on or off. It has long been known that abnormal or missing methylations of DNA building blocks can disturb cell growth and transform a healthy cell into a proliferating cancer cell. For this reason, scientists would like to find out exactly how this process takes place in the cell.
Methylation is “written” on DNA, or “erased” from it, by specific enzymes. Previously, however, it has not been possible to precisely switch the responsible enzymes directly in cells to investigate the subsequent processes in detail. Prof. Daniel Summerer’s research group in the Chemistry and Chemical Biology Department at TU Dortmund University has now been able to do this for the first time – with the help of light. This work could provide a foundation for new insights, never before possible, into the sequence and speed of the processes responsible for the changes cells undergo during embryonic development and the onset of cancer.
How light can be used in DNA methylation
Chemical biologists Dr. Shubhendu Palei and Jan Wolffgramm from the research group use light as a stimulus because it offers very high spatial and temporal resolution and, in addition, is non-invasive – a perfect fit for investigating local and rapid processes in intact cells and whole organisms. First they had to place particular artificial amino acids that can be cleaved by light at key sites on the enzyme. At specific points in time, they then were able to activate the enzymes with brief irradiation in the cells and observe what happens next. In this way, the team investigated the effect of various cancer-relevant mutations on the enzymes’ activity and obtained the first insights into which genes this activity switches on or off, in what sequence, and how strongly. In addition the team managed to develop programmable “writer enzymes” that can selectively methylate specific sequences in the genome, thus enabling the strength of this methylation to be precisely controlled through the duration of the light irradiation.
These studies, published in the Journal of the American Chemical Society and Angewandte Chemie, were conducted within the framework of the project EPICODE. For this project, starting in 2017, the European Research Council awarded Prof. Daniel Summerer an ERC Consolidator Grant of nearly two million euros. Other collaborators on these studies were Prof. Michal Schweiger’s epigenetics and tumor biology research group at the University of Cologne and Dr. Petra Janning of the Max Planck Institute for Molecular Physiology in Dortmund.
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Location & approach
The campus of TU Dortmund University is located close to interstate junction Dortmund West, where the Sauerlandlinie A 45 (Frankfurt-Dortmund) crosses the Ruhrschnellweg B 1 / A 40. The best interstate exit to take from A 45 is “Dortmund-Eichlinghofen” (closer to South Campus), and from B 1 / A 40 “Dortmund-Dorstfeld” (closer to North Campus). Signs for the university are located at both exits. Also, there is a new exit before you pass over the B 1-bridge leading into Dortmund.
To get from North Campus to South Campus by car, there is the connection via Vogelpothsweg/Baroper Straße. We recommend you leave your car on one of the parking lots at North Campus and use the H-Bahn (suspended monorail system), which conveniently connects the two campuses.
TU Dortmund University has its own train station (“Dortmund Universität”). From there, suburban trains (S-Bahn) leave for Dortmund main station (“Dortmund Hauptbahnhof”) and Düsseldorf main station via the “Düsseldorf Airport Train Station” (take S-Bahn number 1, which leaves every 20 or 30 minutes). The university is easily reached from Bochum, Essen, Mülheim an der Ruhr and Duisburg.
You can also take the bus or subway train from Dortmund city to the university: From Dortmund main station, you can take any train bound for the Station “Stadtgarten”, usually lines U41, U45, U 47 and U49. At “Stadtgarten” you switch trains and get on line U42 towards “Hombruch”. Look out for the Station “An der Palmweide”. From the bus stop just across the road, busses bound for TU Dortmund University leave every ten minutes (445, 447 and 462). Another option is to take the subway routes U41, U45, U47 and U49 from Dortmund main station to the stop “Dortmund Kampstraße”. From there, take U43 or U44 to the stop “Dortmund Wittener Straße”. Switch to bus line 447 and get off at “Dortmund Universität S”.
The AirportExpress is a fast and convenient means of transport from Dortmund Airport (DTM) to Dortmund Central Station, taking you there in little more than 20 minutes. From Dortmund Central Station, you can continue to the university campus by interurban railway (S-Bahn). A larger range of international flight connections is offered at Düsseldorf Airport (DUS), which is about 60 kilometres away and can be directly reached by S-Bahn from the university station.
The H-Bahn is one of the hallmarks of TU Dortmund University. There are two stations on North Campus. One (“Dortmund Universität S”) is directly located at the suburban train stop, which connects the university directly with the city of Dortmund and the rest of the Ruhr Area. Also from this station, there are connections to the “Technologiepark” and (via South Campus) Eichlinghofen. The other station is located at the dining hall at North Campus and offers a direct connection to South Campus every five minutes.
The facilities of TU Dortmund University are spread over two campuses, the larger Campus North and the smaller Campus South. Additionally, some areas of the university are located in the adjacent “Technologiepark”.