Objective
The complement system is an ancient and highly conserved component of innate defence against invading pathogens. Its activation occurs via three possible routes: the classical, the lectin and the alternative pathways, resulting in the sequential processing of serine protease zymogens to active enzymes, and ultimately lysis of the pathogen.
The first step in the lectin pathway is the binding of Mannan Binding Lectin (MBL) to an activator surface (e.g. bacteria), which triggers the activation of MBL associated serine proteases (MASPs). However, the compositions of the activation complex and in particular the substrate specificities of MASPs are currently unclear.
There are 3 MASPs, MASP-1, MASP-2 and MASP-3, but only the function of one of them (MASP-2) ha s been defined. There is thus a pressing need to delineate the roles of MASP-1 and MASP-3 and to identify their substrates.
Use of synthetic substrates shows that MASP-1 possesses a thrombin-like specificity and recent work shows that activation of lectin pathway leads to the formation of a fibrin clot. This suggests that the MBL-MASP-1 complex brings about the localised sequestration of a pathogen in addition to its lysis. However, the nature of the components linking MASP-1 to the coagulation pathway remain to be identified.
Therefore, the primary goal of the proposed studies is to use a proteomics strategy to identify physiological substrates for the MASPs, with particular emphasis on MASP-1. Truncated proteins, resulting from digestion of target substrates by the protease in question, will be detected by comparing the profiles of treated- and untreated samples and identified by mass spectrometry.
A further approach using a combinatorial peptide library will define the substrate specificity of MASP-1 in detail and may also lead to the development of specific inhibitors. The proposed studies will provide fundamental new information on key pathways of innate immunity.
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 biochemistry biomolecules proteins proteomics
- natural sciences biological sciences microbiology bacteriology
- medical and health sciences basic medicine immunology
- natural sciences chemical sciences analytical chemistry mass spectrometry
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
You need to log in or register to use this function
Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
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.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP6-2005-MOBILITY-7
See other projects for this call
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.
IIF - Marie Curie actions-Incoming International Fellowships
Coordinator
SOUTHAMPTON
United Kingdom
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.