While at the University of Washington, she pioneered the study of tuberculosis in zebrafish as a close approximation to tuberculosis in humans. This strategy led to a fundamental new biological understanding of how disease develops. Zebrafish larvae are optically transparent and lend themselves to genetic manipulation; by infecting them with their natural pathogen, "Mycobacterium marinum", a bacterium that causes tuberculosis in fish and is a close genetic relative of the bacteria that cause tuberculosis in humans, she could carefully track the infection while manipulating the genes of both the larvae and the bacteria. This approach "enabled a detailed dissection of granuloma formation" (a granuloma is a structure of the immune system made up principally of cells, called macrophages, that ingest bacteria and other foreign particles). In 2010, Ramakrishnan was the senior author of a study which was published as the cover story of "Cell." In 2014, Ramakrishnan joined the faculty of the University of Cambridge as a Principal Research Fellow for the Wellcome Trust and Professor of Immunology and Infectious Diseases. Work in Seattle, and subsequently in Cambridge, led to the discovery of the molecular and cellular details of mycobacterial and host interactions at each step of infection. This yielded fundamental insights that suggest entirely new approaches to treat tuberculosis. Ramakrishnan and her research group showed that two lipids (a type of fatty molecule) on the surface of the mycobacteria work together to enable the bacteria to initially avoid the macrophages that would kill them and instead enter macrophages that provide them a niche for growth. She found that the bacteria then stimulate the formation of granulomas that provide them a safe harbour, in contrast to the normal role of granulomas in protecting the host from the bacteria. Later the infected macrophages in the granulomas die, and this accelerates bacterial growth and promotes the development of the disease. These findings led to host-targeting therapies that show promise in tuberculosis patients. Ramakrishnan and her group tackled the problem of drug tolerance in tuberculosis, and found a drug that inhibits the development of resistance to the standard drugs used to treat the disease. Ramakrishnan later exploited the zebrafish to study leprosy, another devastating disease with morbid neurological consequences. She showed that a "Mycobacterium leprae" lipid causes nerve damage by inciting abnormal responses in the macrophages. In addition to basic science investigations, Ramakrishnan, along with Marcel Behr and Paul Edelstein, reviewed studies concerning the concept of latent tuberculosis in order to determine whether tuberculosis-infected persons have life-long infection capable of causing disease at any future time.