Aarhus Universitets segl

Project description

Aim and perspective

The aim and perspective are to determine structural requirements for recognition of complex polysaccharides and the role of ligand-receptor interactions in the relationships between different cells and organisms. Characterisation of such cellular communication systems is important for understanding factors determining pathogenesis of microorganisms as well as immune responses, symbiosis and cell-to-cell signalling involved in the development and functioning of multicellular organisms.

The centre aims at understanding the interactions between cells and organisms by investigating the role of cell wall glycans and polysaccharides exposed on cell surfaces, and polysaccharide signal molecules secreted as part of a complex interaction between organisms. Our centre focuses on interdisciplinary approaches for understanding biological recognition and response processes at the molecular level.

Carbohydrate signals and extracellular polysaccharides play an important role in cell-to-cell communication processes and are equally important for the organisation of multicellular organisms and the development of their specialised organs and tissues.

The Centre will undertake an integrated functional characterisation of receptor-ligand mechanisms mediating recognition of surface-exposed polysaccharides and subsequent signal amplification. Experimental approaches from chemical biology, bioinformatics, structural biology, functional genomics, proteomics, bioorganic chemistry, and nanobioscience tools will be used in an interdisciplinary environment combining experience from laboratories with complementary research expertise.

The Centre activities will focus on two model organisms: zebrafish and the legume plant Lotus japonicus, and their interactions with pathogenic and symbiotic microorganisms.

Project description

The CARB Centre aims at understanding the interactions between cells and organisms by investigating the role of cell wall glycans and polysaccharides exposed on cell surfaces, and polysaccharide signal molecules secreted as part of a complex interaction between organisms.

The perspective is to determine structural requirements for recognition of complex polysaccharides and the role of ligand-receptor interactions in the relationships between different cells and organisms. Characterisation of such cellular communication systems is important for understanding factors determining pathogenesis of microorganisms as well as immune responses, symbiosis and cell-to-cell signalling involved in the development and functioning of multicellular organisms.

Identification of a new class of LysM lipochitin-oligosaccharide receptors in the rhizobium-legume interaction - coupled with the ability to manipulate both the ligand and the individual domains of the receptor experimentally - has provided new opportunities for functional analysis of polysaccharide receptors. LysM domains are widespread and appear to possess an unusual flexibility in ligand-binding specificity combined with a possible multi-domain mode of ligand binding. Structural and functional characterisation of human, zebrafish and plant LysM domains, their ligand-binding properties and their mechanisms for converting recognition into signalling and cellular responses are therefore of broad scientific interest and a central theme in the Centre's activities.

CARB's approach to unravel cell-to-cell communication will focus on studies of polysaccharide signalling in the legume and zebrafish systems where in vivo activity and in vitro binding can be compared directly. Effective plant and bacterial genetic methods will be used to identify components recognising exo- and lipopolysaccharides exposed on cell surfaces.

To accomplish the Centre's aims an international team will apply interdisciplinary approaches building on their expertise ranging from molecular genetics, carbohydrate chemistry to nanobioscience and bioinformatics. Interactions between synthesised oligosaccharide ligands and receptor binding sites will be determined. Selected recombinant domains including LysM domains from uncharacterised human and zebrafish proteins will be purified and binding of oligosaccharide ligands characterised biochemically and structurally to determine the nature of ligand-binding site interactions. Biochemical binding assays, biophysical methodology, NMR and crystallographic methods will be employed.

The mechanisms of single-membrane-pass receptors translating ligand-binding at extracellular domains into intracellular kinase activation will be characterised in terms of conformational and structural changes. By combining an assortment of genome information and technologies available in the two model organisms, the Centre aims at taking the analysis of signalling processes in multicellular organisms to a new level, distinguishing events in tissues, cells and nuclei. It is the Centre's ambition to establish a unique understanding of fundamental life-processes in animals, humans and plants and provide a scientific environment allowing young scientists to pioneer new developments and do cutting-edge research at a level beyond what could be accomplished by individual participants.