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Research Summary

Our goal is to define the emerging role of RNA and RNA binding proteins (RBPs) in controlling B cell development and the diversification of antibody genes.

We are interested in decoding the mechanisms underpinning diversification of antibody genes, to gain insight into how B cells can effectively fight infections, how these responses change through our lives and the role this plays in age-related immune dysfunction.

Our group is focused on the study of a class of RNA remodelling enzymes called RNA helicases. This interest stems from our discovery on the roles of DDX1 and G-quadruplex (G4) RNA structures in targeting the DNA mutator enzyme AID to the immunoglobulin heavy-chain (IgH) locus, to initiate Class Switch Recombination (CSR) (Ribeiro de Almeida et al, Mol. Cell 2018). RNA helicases are ubiquitous proteins that dynamically remodel the structure of RNA molecules, thereby controlling various steps of gene expression. The dysfunction of these proteins has been implicated in diverse pathologies but their roles in the immune system remain mostly unknown.

We use a number of cellular and molecular biology tools together with mouse genetics, cell culture systems and in vitro biochemical assays, to gain in depth understanding on the role of RNA helicases in B cell biology. We also employ state-of-the-art genomics and proteomics approaches to profile RNA-protein interactions that control developmental stages when B cells undergo recombination at their antibody genes.