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The ubiquitin system

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.

Research Illustration © Malte Gersch​/​TU Dort­mund

Therapeutic opportunities in the ubiquitin system

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 mission

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.

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".

Site Map of TU Dort­mund Uni­ver­sity (Second Page in English).