My research interests encompasses the Ubiquitin Proteasome System predominantly focusing on profiling the activity of Ubiquitin ligases as well as elucidating the biological role of Ubiquitin-like modifier 1 (Ufm1). Ubiquitin, a 76 amino acid protein, is post-translationally attached to the lysines through the sequential action of three enzymes—E1, E2, and E3 and governs nearly every biological process. Having co-developed an activity-based probe (ABP) which can be both transferred through the cascade but also simultaneously covalently traps these enzymes, I’m interested in applying these tools to interrogate the role of these enzymes in ubiquitin biology. However, chemical tools for Ubiquitin-like modifiers akin to those for Ubiquitin have long been lacking necessitating the development of such ABPs. In particular, I expanded the ABP toolkit to include Ufm-1 probes permitting the interrogation of both Ufm-1 conjugating and deconjugating enzymes. Complementing this, I initiated a new line of research investigating the role Ufm-1 in fundamental biological processes using a wide variety of cell biological and biochemical techniques.
After obtaining my Diploma in organic chemistry with emphasis on biochemistry from the Technical University of Berlin with distinction in 2012, I joined the Ovaa lab as a Marie Curie Fellow for my PhD. While my initial project focused on genetic incorporation of unnatural amino acids into proteins, I later co-developed a unique cascading E1-E2-E3 activity-based probe to interrogate the ubiquitin activating, conjugating, and ligating enzymes. In contrast to Ubiquitination and SUMOylation, which have been extensively studied, other Ubiquitin-like modifiers such as UFM1 have been neglected primarily due to lack of tools. To address this disparity, my research interests have recently expanded to studying UFM1. Utilizing both activity-based probes as well as cell biological and biochemical methods, I am currently seeking to decipher its biological role.
Generation of the UFM1 toolkit for profiling UFM1-specific proteases and ligases.
Witting, K.*; van der Heden van Noort, G. J*.; Kofoed C; Talavera Ormeno C.; El Atmioui D.; Mulder MPC.; Ovaa H.;
Angew Chem Int Ed Engl. 2018. doi: 10.1002/anie.201809232.
Total Chemical Synthesis of SUMO and SUMO-based Probes for Profiling the activity of SUMO-Specific Proteases.
Mulder, MPC*; Merkx, R.*; Witting, K.F.; Hameed, D.S.; El Atmioui D.; Lelieveld, L; Liebelt, F.; Neefjes, J; Berlin, I.: Vertegaal, A.C.O.; Ovaa H.
Angew Chem Int Ed Engl. 2018. doi: 10.1002/anie.201803483.
A cascading activity-based probe sequentially targets E1-E2-E3 ubiquitin enzymes.
Mulder, MPC*; Witting, K*; Berlin, I*; Pruneda, JN; Wu, KP; Chang, JG; Merkx, R; Bialas, J; Groettrup, M; Vertegaal, AC; Schulman, BA; Komander, D; Neefjes, J; El Oualid, F; Ovaa H
Nat Chem Biol. 2016. doi: 10.1038/nchembio.2084.