Abstract: We have developed the zebrafish as a model for tuberculosis, exploiting its genetic tractability and optical transparency to study host-mycobacterium interactions in real-time. Starting with a forward genetic screen in the zebrafish, we have identified an enzyme in the eicosanoid pathway that mediates susceptibility to TB in the zebrafish and in humans. Dissection of the pathway in the zebrafish has revealed a pathogenic macrophage cell death pathway that operates through a mitochondrial - ER - lysosomal circuit. The identification of the pathway has led to multiple host-targeting drugs that may be useful in the treatment of TB as well as other inflammatory conditions where this newly-discovered pathway may be operant.

Biography: Professor Lalita Ramakrishnan studies the pathogenesis of tuberculosis using a zebrafish model that her laboratory developed. The optical transparency and genetic tractability of the zebrafish larva have enabled her group to make surprising discoveries about TB pathogenesis and drug tolerance that have immediate clinical implications. Lalita did her medical training in India and then went to the US where she did a PhD in Immunology, medical residency and fellowship in infectious diseases. During her postdoctoral fellowship at Stanford, she developed Mycobacterium marinum as a surrogate for its close genetic relative for Mycobacterium tuberculosis. Her lab has since used zebrafish infected with M. marinum to study the immunopathogenesis of TB. In 2014, she moved from the US to the University of Cambridge where she is Professor of Immunology and Infectious Diseases and a Principal Research Fellow of the Wellcome Trust.