Objective
The lytic activity of cytotoxic T lymphocytes (CTL) plays a central role in the control of viral infection, cancer and homeostasis. The lethal hit of CTL is delivered to the target cell at the level of a highly organized synaptic structure (lytic synapse). How composition and organization of the lytic synapse contribute to the regulation of the lytic activity is largely unknown. The focus of this proposal is to study the lytic synapse of CTL isolated from patients affected by life-threatening primary immuno deficiencies (PID). CTL from patients with genetic mutations causing defects in cytolytic activity are unique natural knock-out models. The following PID will be considered: 1) Wiskott-Aldrich Syndrome due to WASP deficiency, 2) X-linked Lympho-Proliferati ve disease due to SAP deficiency, 3) Familial Hemophagocytic Lymphohistiocytosis due to perforin deficiency. This project will investigate the dynamics of molecular events that occur at the lytic synapse formed between CTL and antigen-loaded antigen-presen ting cells, using time-lapse video recording of the distribution of receptors and signalling components. Analysis of CTL activation and lytic activity will be performed in parallel. These approaches will be combined to lentiviral vector-mediated transfer o f untagged or GFP-tagged constructs encoding WASP, SAP and perforin, in order to visualize these proteins and to correct the lytic function of CTL from PID patients. In addition, a proteomics approach will be employed to identify novel proteins in healthy CTL that could complete our understanding of the lytic synapse architecture and function. This project will provide new insights in the mechanisms regulating CTL activity and in the physiopathology of severe PID. In addition, it will be instrumental for th e development of gene therapy for these severe PID and will have implications for the design of novel therapeutic approaches in which CTL mediated immunosurveillance plays a crucial role.
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.
- medical and health sciences medical biotechnology genetic engineering gene therapy
- medical and health sciences basic medicine immunology
- natural sciences biological sciences genetics mutation
- medical and health sciences clinical medicine oncology
- medical and health sciences basic medicine physiology homeostasis
You need to log in or register to use this function
We are sorry... an unexpected error occurred during execution.
You need to be authenticated. Your session might have expired.
Thank you for your feedback. You will soon receive an email to confirm the submission. If you have selected to be notified about the reporting status, you will also be contacted when the reporting status will change.
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.
FP6-2004-MOBILITY-8
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.
Coordinator
PARIS
France
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.