Msc. Gabrielle van Tilburg

Research:

I work on biophysical screening methods to detect linkage specific ubiquitin binding to bio-informatically predicted ubiquitin binding domains (UBDs). Ubiquitin is a post-translational modifier which can be conjugated to itself via either one of its 7 internal lysine residues or its N-terminus, giving rise to 8 different ubiquitin isoforms. Understanding the complexity and importance of this diverse signal is a major challenge vital to many cellular processes.  In order to discover which UBDs have preference for a certain ubiquitin linkage type, I use chemically synthesized diubiquitins representing all 8 different ubiquitin isoforms and techniques such as fluorescence polarization and surface plasmon resonance. In more recent work, I contributed to understanding the complex landscape of ubiquitin signaling by synthesizing biotinylated, non-hydrolyzable diubiquitin baits which were used as pulldown tools to identify ubiquitin linkage specific binding proteins in cells by tandem mass spectrometry. One linkage-specific protein identified was the deubiquitinase UCHL3, which binds with high affinity and specificity to K27 diubiquitin. In current efforts I am characterizing the consequence of this intriguing new complex. 

Curriculum Vitae:

I obtained my bachelor degree in Life Sciences at Avans Hogeschool in 2009 and in 2012 I graduated cum laude from Vrije Universiteit Amsterdam with specializations in Cell Biology and Biochemistry. During my internships, I have always been interested in cancer research, protein biochemistry and post-translational modifications. Topics included SUMOylation of the transcription factor TEL, regulation of Ezrin via phosphorylation and ubiquitin binding domains. As a PhD student in the Ovaa lab, I work on gaining more insight into the functions of all 8 homotypical ubiquitin isoforms and the selective manner in which they bind their target proteins. 

Publications

  • • Synthetic and semi-synthetic strategies to study ubiquitin signaling.

    GBA van Tilburg, AF Elhebieshy, H Ovaa

    Curr Opin Struct Biol. 2016 Jun, 38:92-101, doi: 10.1016/j.sbi.2016.05.022

  • • An interaction landscape of ubiquitin signaling.

    X Zhang*, AH Smits*, GBA van Tilburg*, H Ovaa, W. Huber, M. Vermeulen

    Mol Cell. 2017 Mar 2; doi: 65(5):941-955.e8

  • • Proteome-wide identification of ubiquitin interactions using UbIA-MS.

    X Zhang*, AH Smits*, GBA van Tilburg*, H Ovaa, W. Huber, M. Vermeulen

    Nature Protocols 13, p 530–550 (2018) Doi: https://doi.org/10.1038/nprot.2017.147

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