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Content archived on 2024-05-27

AID in adaptive immunity and beyond

Objective

This proposal revolves around the enzyme Activation-Induced Deaminase (AID). AID plays a pivotal role in adaptive immunity because it is essential to introduce the lesions in the immunoglobulin genes that ultimately lead to somatic hypermutation (SHM), class switch recombination (CSR) and immunoglobulin gene conversion (Ig GC). However, its mutagenic ability has a pernicious side effect and AID has been implicated in B lymphomas and other neoplasias. Finally, because AID belongs to a family of cytidine deaminases including members with anti-retroviral properties due to their targeting of viral cDNA, cytidine deamination of DNA is yet another unforeseen link between innate and adaptive immunity. Here, I plan to use classical molecular approaches and genetically engineered mice to discover AID co-factors for CSR, to address the rules governing AID targeting to the immunoglobulin loci and to establish murine models to evaluate the impact of ectopic expression of AID. In addition, I describe how a functional assay I developed previously to characterize orthologous AID forms can be adapted to clone molecules from distant species able to introduce lesions in DNA, with the goal of better elucidating the evolution of somatic DNA modification.

Call for proposal

FP7-PEOPLE-IRG-2008
See other projects for this call

Coordinator

FUNDACAO CALOUSTE GULBENKIAN
EU contribution
€ 100 000,00
Address
AVENIDA BERNA 45A
1067-001 LISBOA
Portugal

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Region
Continente Área Metropolitana de Lisboa Área Metropolitana de Lisboa
Activity type
Research Organisations
Administrative Contact
António Coutinho (Prof.)
Links
Total cost
No data