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Toll-like receptors: a target for many therapeutic applications
Toll-like receptors (TLRs) form a class of proteins that play an important role in the innate immune system, important in host defense against infections. Moreover, TLRs play a role in other immunological processes and disruption may lead to various diseases like rheumatoid arthritis, COPD and Crohn's disease. Within this project the opportunities for TLRs as a drug-target are explored.
The broad interest for the role of the TLR protein family has led to TI Pharma's largest project, in which scientists from many different disciplines participate. Some work on the development of tools that can modulate the function of TLRs. For instance, probiotics are being selected and small molecules are being generated that specifically affect TLR activity. Also, the possibilities for improvement of vaccination strategies using TLRs are being explored. Other researchers investigate the role of TLRs in specific disease areas like cancer, cardiovascular and autoimmune disease. The knowledge obtained through this type of basic research together with the tools developed to interfere in TLR functioning will provide insight in the possibilities for further drug development based on TLR signaling.
Full project title: Exploitation of toll-like receptors in drug discovery
Start date: March 2008
End date: March 2012
Goal: Identifying and making toll-like receptor modulators and developing potentially relevant therapeutic applications
Principal investigator: Anja Garritsen, MSD
Project size: 41 FTE's
Background: Innate immune system
Partners: ISA Pharmaceuticals, Leiden University, Leiden University Medical Center, Maastricht University, Danone Research, MSD, Radboud University Medical Center, TNO, University Medical Center Utrecht
The innate immune system is important for the host defense against infection by other organisms. The system provides immediate defense, but it does not result in long-lasting immunity against the source of the infection. In other words, the innate system does not develop over time, in contrary to the adaptive immune system.
During infection, the innate immune system recruits immune cells to the site, activates a number of processes to identify the cause of infection (f.e. bacteria) and subsequently ensures these are removed. Finally, the innate immune system activates the adaptive immune system to accomplish immunity for future infections.
Theo Plantinga (project D1-101)
Modulation of inflammationby genetic variation in innateimmunity
May Young Lin (project D1-101)
Discovery of dormancy associated antigens of Mycobacterium tuberculosis
Marthe Walvoort (project D1-101)
On the reactivity & selectivity of donor glycosides in glycochemistry & glycobiology
Ben van den Brand (project D1-101)
Delineating the role of Toll-Like Receptor 4 activation and its signaling in experimental arthritis
Rob Mariman (project D1-101)
Probiotic bacteria and the immune system: mechanistic insights and therapeutic implications
Jacco Karper (project D1-101)
Damage Associated Molecular Patterns and Toll Like Receptors in Inflammation mediated Vascular Remodeling
Na Rae de Jong (project D1-101)
Development of Synthetic Procedures Towards Immunostimulating Carbohydrates
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