Principal Investigator Tania Baker
Professor Baker's research focuses on the mechanism and regulation of two families of protein machines: the Clp/Hsp100 ATPases that catalyze protein unfolding and the disassembly of protein complexes, and the transposase/integrase family of recombinases.
Transposable elements have successfully invaded all forms of life, promoting their movement from one DNA site to another by a type of genetic recombination called transposition. The impact of transposition on genomic architecture and human health is immense. Many transposable elements can insert into any DNA sequence and are thus a common source of mutations. The spread of antibiotic-resistance genes is largely a result of transposable elements moving throughout bacterial populations. Furthermore, retroviruses, including HIV, integrate into the host chromosome via a mechanism nearly identical to transposition. A related recombination reaction is also responsible for assembly of the immunoglobulin and T cell receptor genes during development of the immune system.
Work on DNA transposition is centered on studies of bacteriophage Mu, which transposes extraordinarily frequently, making it an excellent system for analyzing the mechanism of transposition. Our interest in proteins that catalyze the disassembly and unfolding of other proteins arose directly from studies of Mu transposition. The ClpX chaperone, a member of the Clp/Hsp100 ATPase family (a subfamily of the AAA+ ATPases), is required to disassemble the transposition machinery after recombination is complete. Clp/Hsp100 proteins are present in bacteria, plants, and animals, where they are involved in intracellular degradation, protein transport into organelles, solubilization of protein aggregates, and the dismantling of supramolecular assemblies.