DNA Editing Laboratory
Current and future research
AID (activation induced deaminase), a protein required for the formation of an intact immune system, was the first enzyme to be described to deaminate the cytosine residue in single stranded DNA forming the non-standard base of deoxy-uracil. Over- or mis-expression of AID can lead to tumour formation, whereas lack of AID can lead to immunodeficiency. AID expression during development is thought to invoke epigenetic alterations.
DNA stability is one of the principle elements for survival. Aberrant DNA rearrangement, recombination, or even point mutations can have dire pathogenic consequences. The recent discovery of a family of evolutionarily conserved proteins that actively undermine this principle by deaminating dC residues in DNA has lead to the further understanding of the mechanism of immunoglobulin diversification, identification of a novel means of eliminating viral infection, a new mechanism for the reprogramming of the epigenetic status of a cell, and also pointed at a new means for the induction of cancer.
There are approximate 10 members of the AID/APOBEC family in the human genome. In the cytoplasm they serve to eliminate foreign DNA, including retroviruses. In the nucleus, AID is responsible for the initiation of immunoglobulin diversification. Recently we were able to show:
- the expression of AID during genome wide demethylation, and
- AID can deaminate meCpG in vitro as well as in E. coli
Raising the possibility that AID can act as an initiator of to reprogram the epigenetic status of a cell.
Future projects:
To understand the exact mechanism that regulates the expression and targeting of the deaminase proteins to their sub-cellular compartments. Gene-knock-out and knock-in technology will be used to follow localisation as well as protein-protein interactions of AID. Serving as a basis to understand the pathways leading to the activation and inactivation of immunoglobulin diversification machinery, as well as a means to identify the targeting of AID during epigenetic reprogramming.
