Post-translational modifications (PTMs) play a central role in coordinating intracellular processes. The ubiquitin protein is a post-translational modifier that can be attached to lysine side chains of substrate proteins by a cascade of E1/E2/E3 enzymes.
Signalling through ubiquitination is counteracted by specialised proteases termed de-ubiquitinating enzymes (DUBs), which selectively cleave the isopeptide bond between ubiquitin moieties in chains or between ubiquitin and substrate proteins.
More than 100,000 ubiquitinated sites have been mapped in the human proteome. Additional information can be encoded through differently linked ubiquitin chains and the interplay with other PTMs. This generates a complex and versatile intracellular signalling system with need for tight regulation of all enzymatic components.
Aberrant ubiquitin-dependent signaling has been implicated in the development of cancer, neurodegenerative and inflammatory diseases. Recent efforts to modulate DUB activity with small molecules have shown this to be a powerful strategy to amplify ubiquitin-dependent signalling and thereby alter key cellular processes, but compounds with high specificity and activity are lacking in many cases.
Moreover, for most pathologies it is unclear which DUB could be targeted for therapeutic purposes as for many insights into their functional roles and endogenous substrate recognition mechanisms are scarce.
Our lab aims to understand mechanisms by which proteolytic enzymes in the Ubiquitin system operate, and to exploit these insights towards novel therapeutic approaches.
We believe that one promising way to shed light on the underlying complexity of the Ubiquitin system is to study its proteolytic components on the molecular and structural level.
We are guided by the vision that small molecules, which specifically target components of the ubiquitin system, can complement these efforts and provide a powerful means to indirectly modulate the levels of disease-relevant proteins in cells that are difficult to target directly, such as oncogenic transcription factors or frequently mutated enzymes.
Ultimately, we aim to molecularly connect these enzymes to pathologically relevant pathways and introduce well-characterised small molecule tools to interrogate their protein function in biological systems.
To achieve these goals, we work as a multidisciplinary team, integrating chemical biology, organic chemistry, protein biochemistry, structural biology and cellular assays.
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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 Campus Süd), and from B 1 / A 40 "Dortmund-Dorstfeld" (closer to Campus Nord). 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 Campus Nord to Campus Süd by car, there is the connection via Vogelpothsweg/Baroper Straße. We recommend you leave your car on one of the parking lots at Campus Nord 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 H-Bahn is one of the hallmarks of TU Dortmund University. There are two stations on Campus Nord. 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 Campus Süd) Eichlinghofen. The other station is located at the dining hall at Campus Nord and offers a direct connection to Campus Süd every five minutes.
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 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".