Research

The research carried out in our department is focussed on the molecular aspects of cellular stress and autoimmunity.

 

Characterisation and function of autoantigens

Patients suffering from autoimmune diseases produce antibodies to self-proteins, which are referred to as autoantigens. In general, such autoantigens are macromolecules which have important cellular functions. We study the structure and function of autoantigens involved in the synthesis and degradation of RNA and proteins.

We also address the question why tolerance to self-proteins is lost in autoimmunity. Our studies are based on the hypothesis that unusual posttranslational modifications play a role in the generation of autoreactive antibodies, and we believe that such modifications play an important role in the initiation of autoimmunity. The knowledge obtained on the structure and modifications of autoantigenic molecules is used for the development of autoimmune diagnostics.

 

Small stress proteins: structure, function and pathology

The cell protects itself against stress, like heat, radicals or radiation, by synthesizing a set of special proteins, amongst which the ‘small heat-shock proteins’ (sHsps). The sHsps have in vitro chaperone activity: i.e., they prevent the aggregation of other proteins. In vivo, they enhance the stress-tolerance of cells. Man has ten different sHsps, which are most abundant in the eye lens, in heart and muscles. In the brain they become induced in Alzheimer’s disease and multiple sclerosis. The three-dimensional structures and working mechanisms of the various sHsps are poorly understood. The structure, chaperoning mechanism en cytoprotection of the sHsps, and their roles in diseases, ageing and apoptosis is being studied.

 

A chemical biology approach to study protein quality control

Defective quality control mechanisms may result in toxic protein aggregates that accumulate in the cell. Besides understanding how cells handle such protein aggregates, a major focus is to develop ‘smart’ molecules that targeting them for degradation by autophagy or specific proteases.

 

Projects

The human ribonuclease RNase MRP and RNase P: from structural similarity to functional diversity

A ‘plug and play’ approach to study biomolecular interactions on solid surfaces

The role of the aromatic cage in reader proteins on trimethyl-lysine recognition

 

 

 

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