Monique MULDER

Supervisor Project : Expanding chemical technologies towards SUMO and NEDD8-based reagents. This project relates to all WPs, allowing the generation of a broadly applicable scale of reagents.

 

LUMC Leiden, Netherlands
+31 (0)71 52 687 32
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Partner Lab

The LUMC is a university medical centre for research, education and patient care with a high quality profile and a strong scientific orientation and ranks as the 6th best medical research institute in Europe (Shanghai 2015). It has a unique research practice, ranging from pure fundamental medical research to applied clinical research. This enables LUMC to offer patient care and education that is in line with the latest international insights and standards – and helps it to improve medicine and healthcare. The LUMC participates in the League of European Research Universities (LERU), a strong international network of 21 renowned research universities (www.leru.org). LUMC is also a member of the Coimbra group, placing it amongst the most prestigious universities in Europe.

 

About

Monique Mulder is trained as an organic/medicinal chemist and nowadays takes advantage of chemistry in combination with chemical biology techniques to interrogate the complex Ubiquitin Proteasome System (UPS). Post-translational modification of proteins with ubiquitin (Ub) is a dynamic process that regulates nearly every single cellular process. A cascade of E1, E2, E3 enzymes is responsible for the defined conjugation of a Ub to a substrate, whereas removal of the Ub is regulated by proteases termed deubiquitylating enzymes (DUBs). Monique developed a novel activity-based probe (ABP) to study substrate context in the monitoring of DUB activity, the first ligase probe that can travel and trap the full conjugation machinery and more recently ABPs based on ubiquitin-like proteins. Complementing this, she initiated a new line of research investigating the role of the UPS in neurodegeneration. Utilizing both activity-based probes as well as biochemistry and cell biology techniques, she is currently seeking to unravel the role of ubiquitination and the proteasome in neurodegeneration. The aim of her research is to discover unique components of the UPS that could become therapeutic targets in the future.

Summary of the Project

Monique Mulder took over the supervision of Huib Ovaa's project. The Ub/UbL code is translated into biochemical action through interaction with specific binding domains. These domains specifically bind to Ub or UbLs that can be present in larger chains. In order to interfere with chain signalling, modulation of these interactions is an interesting but so far unexplored option. It is important to have good methods available that help determine where and when such domains interact. Currently we can efficiently generate a board scale of Ub-based research reagents based on chemical synthesis. This project aims to translate synthetic methods that allow the generation of Ub-based reagents, probes and chains towards chemical methods to do the same for UbL proteins, starting with SUMO-1, -2 and -3 as well as NEDD8. The resulting UbL reagents will then be used in collaboration with other members of the network to study Ub, SUMO and NEDD8 biology.