Alfred Vertegaal’s research interest is to delineate signal transduction by Small Ubiquitin-like MOdifiers (SUMOs). SUMOylation is critical for eukaryotic life and regulates a wide variety of cellular processes including transcription, pre-mRNA splicing, translation, cell cycle progression, transport, and DNA repair.
The SUMO proteome analysis has uncovered hundreds of SUMO target proteins. SILAC technology is employed to study SUMOylation dynamics. His group has developed novel methodology to study protein SUMOylation in a site-specific manner at a proteome wide level. Over 4,300 SUMO-2 acceptor lysines in over 1,600 endogenous target proteins were identified and this information was used to refine the SUMOylation consensus motif.

Ivan Dikic's research focuses on deciphering molecular mechanisms of cellular signaling pathways, which have a high relevance to human diseases such as cancer, neurodegenerative disorders and inflammation. Early on, he started to focus on ubiquitin to understand how this modification controls multiple cellular functions, and managed to prove a concept of ubiquitin signal recognition by specialized domains serving as specific receptors. More recently, his team has revealed the functions of linear ubiquitin chains in pathogen defense and overall immune response.
He expanded his research to the field of selective autophagy, recognizing the enormous impact of the LC3/GABARAP signaling network displaying striking mechanistic similarities to ubiquitin. One major focus is on the crosstalk between autophagy and endocytic machineries, and in this context he has gained fundamental insight in autophagic processes at the endoplasmic reticulum (ER-phagy).

Her research aims at understanding the mechanisms and signals by which the ubiquitin and SUMO systems promote damage tolerance and limit the accumulation of unwanted mutations. DNA damage bypass, also called postreplication repair, is controlled via posttranslational modification of the replication factor PCNA. Whereas monoubiquitylation activates translesion synthesis by damage-tolerant DNA polymerases, polyubiquitylation via lysine 63-linked chains is required for an error-free pathway of damage avoidance possibly involving template switching. PCNA is also sumoylated in a damage-independent manner, which prevents unwanted recombination events during replication and allows the ubiquitin-dependent reactions to proceed upon replication fork stalling.
Using a combination of molecular and cellular biology, biochemistry and classical genetics, her team investigates the factors that influence the choice of bypass pathway and determine the efficiency and accuracy of damage processing, the molecular signals that trigger the each of the modifications at the appropriate time within the cell, the mechanisms by which the ubiquitin and SUMO conjugation factors recognise and modify their substrates, and the coordination of damage bypass with DNA replication, chromatin dynamics and other pathways of genome maintenance.

The objective of Ron’s group is to establish the role of ubiquitin and ubiquitin-like proteins in important biological processes. They presently have projects linking SUMO modification to ubiquitylation, in stress responses and DNA damage. Caenorhabditis elegans has been used to establish the contribution of SUMO to a timely and accurate cell division. During C. elegans oocyte meiosis, a multi-protein ring complex (RC) localized between homologous chromosomes, promotes chromosome congression.
Dynamic SUMO modification and the presence of SIMs in RC components generate a SUMO-SIM network that facilitates assembly of the RC. A key role for SUMO and ubiquitin was uncovered in mediating the effects of arsenic when it is used therapeutically in the treatment of Acute Promyelocytic Leukaemia. Recently determination of the structure of a RING E3 ligase and ubiquitin-loaded E2 complex primed for catalysis has revealed the mechanism of ubiquitin modification. We developed a method that enabled proteome-wide identification of sumoylated lysine residues that enables the detection of thousands of sites of SUMO modification in a single experiment. This technology is flexible and can be adapted for use with any Ubl.