Objective
Recognition of glycoconjugates is an important event in biological systems. In the immune system in particular, many processes are mediated by protein- carbohydrate interactions. The objective of this proposal: is to develop tools that can be used to analyze and to modulate these interactions. Central to our proposal is the biotechnological preparation of oligosaccharide-based compounds that will help to control the proper functioning of the immune system.
We shall focus on two model systems: (a) the phenomenon of hyperacute vascular rejection that is observed in xenograft transplantation, and (b) the binding of human leukocytes to endothelial cells in an inflamed tissue. Both systems are of great importance to human pathology. In view of the current shortage of organs, the transplantation of pig organs to humans is being considered as an alternative. However, the presence of natural anti-carbohydrate antibodies in the human circulation constitutes a major barrier to crossspecies transplantation. Absorption or blocking of the antibodies will help to avoid hyperacute rejection.
Cell surface carbohydrates also play a role in the extravazation of human leukocytes at a site of inflammation. The first step towards extravazation involves receptors on the endothelial cell-surface that recognise and bind glycosylated structures on the surface of leukocytes. Competing carbohydrates could serve as a new generation of anti-inflammatory drugs.
The present proposal describes a multi-disciplinary approach to produce immunoreactive compounds that will be used to facilitate xenograft transplantation, and to control inflammation. To thoroughly understand, and to be able to interfere with carbohydrate-dependent interactions, well-defined carbohydrate ligands must be available. By a combination of organic chemical and enzyme-assisted synthesis we shall be able to rapidly synthesise a broad range of oligosaccharides linked to the appropriate aglycon spacers and carriers. These compounds will be tested for biocompatibility, and biological activity in- vitro and in-vivo. Molecular modeling will be applied to improve their efficiency, and to study their interaction with receptors and antibodies. Our long term goal is to contribute to the success of xenotransplantation, and to the design of a novel generation of anti-inflammatory drugs. Our proposal is based on a number of recent technical advances in the fields of transplantation medicine, carbohydrate analysis, the molecular genetics of glycosylating enzymes, biotechnology, conformational analysis and computer-assisted modeling, and biological testing in-vitro. It allows environmentally friendly production of highly specific, immunoactive glycoconjugates, to be used in human medicine to improve quality of life. Benefits for the EC: Our current and future studies are precompetitive in character, and will produce knowledge which will form the basis for the development of marketable products. The European network that we intend to set up forms a logical extension of our various ongoing collaborations, and will be a forum for the exchange of knowledge within the EC. It will stimulate a close interaction between groups each having a very different expertise, but sharing an interest in the application of glycobiology in human pathology. In view of the young age of the field of glycobiology, the number of groups involved nationally is limited, and therefore a project as presented here can only be successfully undertaken on a structural international basis. By integration and cooperation on a European level, research will be more cost-efficient, duplication of efforts is avoided, and a coordinated, cohesive European approach will be achieved.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences molecular biology molecular genetics
- medical and health sciences basic medicine immunology
- natural sciences biological sciences biochemistry biomolecules carbohydrates
- medical and health sciences basic medicine pathology
- medical and health sciences clinical medicine transplantation
You need to log in or register to use this function
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Data not available
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Coordinator
1081 BT Amsterdam
Netherlands
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.