John McKinney

Mission Research in the MCKINNEY LAB is focused on the mechanistic basis of Mycobacterium tuberculosis persistence in the context of host immunity and antimicrobial therapy. Our research covers four areas:COUNTER-IMMUNITY. Host immunity is usually sufficient to contain M. tuberculosis infection, but not to eradicate infection. We seek to identify the mechanisms that M. tuberculosis uses to evade or counter the impact of the host immune response.IN VIVO METABOLISM. In recent years, central metabolism has emerged as an attractive target for antimicrobial drug discovery. We seek to identify the catabolic and anaplerotic pathways that are required for M. tuberculosis growth and persistence during infection of the mammalian host.ANTIBIOTIC TOLERANCE. Tuberculosis is notoriously refractory to antimicrobial therapy. We seek to understand the mechanistic basis of M. tuberculosis persistence in the antibiotic-treated host, and the epigenetic control of cell-to-cell variation in antibiotic sensitivity.CELL CYCLE DYNAMICS. M. tuberculosis is also notorious for its unusually slow intrinsic growth rate in vitro and in vivo (the minimum population doubling time is about 20 hours in either environment). We seek to understand why M. tuberculosis grows so slowly and to identify the physiologic adaptations that are required for slow growth.Our experimental approaches include molecular genetics, tissue culture and animal infection models, computational modeling, mass spectrometry, microfluidics, and time-lapse fluorescence microscopy. Professor John McKinney received his Ph.D. from The Rockefeller University (New York, NY) in 1994 for studies on cell cycle regulation in Saccharomyces cerevisiae in the laboratory of Fred Cross. From 1995 to 1998, he was a postdoctoral fellow in the laboratory of William Jacobs at the Albert Einstein College of Medicine (Bronx, NY), where he studied mechanisms of persistence in Mycobacterium tuberculosis. In 1999, he returned to Rockefeller University to establish his own laboratory as an Assistant (1999-2004) and then Associate (2004-2007) Professor. In July 2007, the lab relocated to the Global Health Institute in the School of Life Sciences at the École Polytechnique Fédérale de Lausanne (EPFL) in Switzerland, where McKinney is Professor and Head of the Laboratory of Microbiology and Microsystems (LMIC). Our research focuses on understanding the mechanistic basis of bacterial persistence in the context of host immunity and antimicrobial therapy, using M. tuberculosis as a "model" system. Education PhD | Molecular Genetics 1994 – 1994 The Rockefeller University Teaching & PhD PhD Students Gauri Rshikesan Paduthol, Ashim Kumar Dubey Past EPFL PhD Students Meltem Elitas, Cyntia De Piano, Muhittin Emre Özdemir, Ekaterina Gelman, Matthieu Delincé, Amanda Verpoorte, Katrin Esther Schneider, Joëlle Ven, Gaëlle Vuaridel Thurre, Kunal Sharma, Thomas Simonet, Ophélie Rutschmann, Frédéric Normandeau, Braun Esther Past EPFL PhD Students as codirector Mélanie Hannebelle Courses Microbiology BIO-372 This course will provide an introduction to fundamental concepts in microbiology. Special emphasis will be given to the surprising and often counter-intuitive physical world inhabited by microorganisms. Planetary health BIO-413 This course provides an overview of global environmental change through the perspective of the planetary boundaries and examines how human health is interlinked with social and ecological contexts.