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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.

Field of science

  • /engineering and technology/civil engineering/structural engineering/structural health monitoring
  • /natural sciences/biological sciences/biochemistry/biomolecules/proteins/enzymes

Call for proposal

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

Funding Scheme

MC-IRG - International Re-integration Grants (IRG)

Coordinator

FUNDACAO CALOUSTE GULBENKIAN
Address
Avenida Berna 45
1000 Lisboa
Portugal
Activity type
Research Organisations
EU contribution
€ 100 000
Administrative Contact
António Coutinho (Prof.)