We work on the rearrangement of immunoglobulin and T-cell receptor genes, which is essential for the development of lymphoid cells, and for the ability of the immune system to fend off multiple types of attack. This DNA reshuffling, known as V(D)J recombination, makes it possible for us to produce antibodies and T-cell receptors with millions of different specificities. The process is unique in sharing many properties with mobile genetic elements called transposons. It also has similarities with the repair of radiation damage to DNA. Our aim is to understand V(D)J recombination as thoroughly as possible, and then apply this knowledge to the immune system. We now focus on the RAG1 and RAG2 proteins, which work together to break the DNA at specific sites to start recombination. Most recently, we are using structural methods (in collaboration with Dr. Wei Yang of this laboratory) to understand the activities of the RAG proteins. We recently published the first detailed structure of the RAG1-RAG2 complex. We are also learning about covalent modifications of RAG1 by auto-ubiquitylation and by phosphorylation, which alter its activity.