Dr Claudia Ribeiro de Almeida

Babraham Institute

Position: Group Leader
Personal home page: https://www.babraham.ac.uk/our-research/lymphocyte/claudia-ribeiro-de-almeida

PubMed journal articles - click here

Dr Claudia Ribeiro de Almeida is pleased to consider applications from prospective PhD students.

Research description

B-lymphocytes are cells of the immune system responsible for the production of antibodies, and do so by employing hazardous mechanisms of somatic DNA mutation and DNA deletion-recombination with remarkable efficiency. Increasing evidence suggests a significant contribution of RNA-mediated processes in regulating antibody gene rearrangements, although only a few RNA-binding proteins (RBPs) have been implicated so far.

Our research focuses on the role of RNA helicases, an important class of RBPs involved in remodelling RNA secondary structure and ribonucleoprotein complexes. We have found the RNA helicase DDX1 to be required for Class Switch Recombination, to modulate R-loop (RNA:DNA hybrid) and G-quadruplex (G4) structures present in CSR-induced long non-coding RNAs (Ribeiro de Almeida, 2018). These findings support a role for G4 RNA and DDX1 in targeting the CSR-catalysing enzyme activation-induced cytidine deaminase (AID) to the immunoglobulin heavy-chain (IgH) locus and initiate DNA mutation.

At present we are working on understanding how DDX1 and other RNA helicases are involved in regulating AID targeting specificity during B-lymphocyte immune responses. These studies will elucidate the fundamental molecular mechanisms underlying the ability of B-lymphocytes to mount effective antibody responses against pathogens, while maintaining genome stability and cellular homeostasis.

Research Programme or Virtual Institute
Fundamental Biology of Cancer
Secondary Programme
Haematological Malignancies Virtual Institute
RNA helicases
Class Switch Recombination
V(D)J recombination

Key publications

Ribeiro de Almeida C, Dhir S, Dhir A, Moghaddam AE, Sattentau Q, Meinhart A, Proudfoot NJ.
RNA Helicase DDX1 Converts RNA G-Quadruplex Structures into R-Loops to Promote IgH Class Switch Recombination.
Mol Cell. 2018 May 17;70(4):650-662.e8. doi: 10.1016/j.molcel.2018.04.001.

Ribeiro de Almeida C, Hendriks RW, Stadhouders R.
Dynamic Control of Long-Range Genomic Interactions at the Immunoglobulin κ Light-Chain Locus.
Adv Immunol. 2015;128:183-271. doi: 10.1016/bs.ai.2015.07.004.

Ribeiro de Almeida C, Stadhouders R, Thongjuea S, Soler E, Hendriks RW.
DNA-binding factor CTCF and long-range gene interactions in V(D)J recombination and oncogene activation.
Blood. 2012 Jun 28;119(26):6209-18. doi: 10.1182/blood-2012-03-402586.

Ribeiro de Almeida C, Stadhouders R, de Bruijn MJ, Bergen IM, Thongjuea S, Lenhard B, van Ijcken W, Grosveld F, Galjart N, Soler E, Hendriks RW.
The DNA-binding protein CTCF limits proximal Vκ recombination and restricts κ enhancer interactions to the immunoglobulin κ light chain locus.
Immunity. 2011 Oct 28;35(4):501-13. doi: 10.1016/j.immuni.2011.07.014.