Scientists expose protein responsible for allergic diseases

(04-04-2017) Scientists at VIB-UGent have managed to unravel the functioning of what is thought to be the ‘master protein’ that drives a range of widespread allergic diseases, such as asthma and eczema.

Millions of people worldwide suffer from common allergies – ranging from light asthmatic symptoms to severe atopic dermatitis, a frequent form of eczema.  Such diseases cause a heavy burden in the quality of life of people suffering from them, and at the same impose a gigantic socioeconomic and healthcare footprint. The exact causes of such diseases are not known yet, although the answer probably lies in a combination of genetic, molecular, and environmental factors. While some treatments may reduce the severity and frequency of symptoms, a comprehensive cure has yet to be found.

New therapeutics against allergic diseases

To tackle the complex issue of studying diseases at the molecular level, professor Savvas Savvides of the VIB-UGent Center for Inflammation Research coordinated a multidisciplinary team spearheaded by Dr. Kenneth Verstraete, that united expertise from three VIB-UGent research centers, Ghent University, the University of Antwerp, The Pontifical Catholic University of Peru, and the University of Toulouse in France.

The team focused on understanding the molecular and structural mechanism of how a protein called TSLP interacts with its two molecular receptors at the cell surface. A key undertaking has been the elucidation of the three dimensional structure of the molecular assembly mediated by TSLP.  In parallel, the team developed and characterized a novel protein-based inhibitor of TSLP that can efficiently capture TSLP to prevent its association with its natural receptors on the cell surface. In this way, the bioactivity of TSLP can be blocked. The study has been supported by funding from national and international sources, as well as research infrastructure at the European level.

Prof. Savvas Savvides (VIB-UGent): “For the first time, we have obtained detailed snapshots of TSLP’s function. More specifically we unraveled how it mediates the protein assembly at the cell surface responsible for several atopic diseases, including asthma and atopic dermatitis. TSLP has been the focus of many prominent academic laboratories worldwide, as well as major pharmaceutical companies. This knowledge offers them a new tool for therapeutic intervention. Our study proves that basic research at the molecular level is the pillar for developing new therapeutic strategies.”

Prof. Rudi Beyaert (VIB-UGent): “The detailed structural and biochemical insights are a key source of information for understanding and optimizing the potency of our inhibitory molecule against TSLP. We are very excited about the implications and promise of this work.”


The academic article: Structure and Antagonism of the Receptor Complex Mediated by Human TSLP in Allergy and Asthma, Verstraete et al., Nature Communications 2017

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