When Makarova's husband moved to the US to work with Eugene Koonin in the National Center for Biotechnology Information, Koonin found Makarova a position as research fellow at the Uniformed Services University of the Health Sciences, studying Deinococcus radiodurans, a bacterium that can survive highly extreme conditions. In 2001, Koonin hired Makarova to join him at the National Center for Biotechnology Information. At the center, beginning in 2006, Makarova and her co-workers investigated the CRISPR-Cas9 system and its biological function as a bacterial immune system.