Genetic diversity is created by mutations in the genome of all living organisms. When combined with natural selection, this diversity underpins evolution and adaptation to the environment. The Laboratory of Mechanisms of Genetic Diversity aims to understand systems in which mutations are actively generated and fixed in particular regions of the genome of a cell.
In particular, we are studying immunoglobulin (Ig) gene diversification, a set of processes that allow the affinity maturation of antibodies that is important for immunological memory and change the isotype of the antibodies from IgM to IgG, IgE or IgA, which confers new biological properties to the antibody molecule. We are focusing in the interplay between the initiating enzyme Activation Induced Deaminase (AID), a mutator that converts deoxycytidine into deoxyuridine by enzymatic deamination acting preferentially in defined regions of the Ig genes, and the repair pathways that normally remove uracil from DNA. Of major importance and central to our research is the enzyme uracil-DNA glycosylase UNG, required for many of the mutagenic outcomes of Ig diversification despite being usually an antimutagenic enzyme.
A combination of genetic, molecular and biochemical techniques are applied to study Ig diversification in cellular systems as well as using mouse models.
We want to understand how the action of AID is regulated and coordinated with UNG in order to favour mutation over repair, yet still maintaining overall genome stability. We also want to understand how deviations from this balance can lead either to immunodeficiency or to B cell lymphomas and perhaps other types of cancers.
For a more detailed description and further information, please visit our lab webpage.