Molecular Genetics of Mycobacteria
Professor Yossef Av-Gay is a microbiologist engaged in basic research mastering microbial genetics and biochemistry of microorganisms. Prof. Av-Gay’s research focuses on translational research of bacterial pathogens aiming at anti microbial drug development. His first major contribution to the field of Tuberculosis (TB) research was the identification of the “Eukaryotic – like” protein kinases of Mycobacterium tuberculosis, a new family of protein which play a role in the bacterial adaptive gene expression and cross-talk with the infected human macrophages. This discovery opened a new field of research into signaling elements of M. tuberculosis and has gained him recognition as a leader in mycobacterial signal transduction research.
In collaboration with industry his group has shown that small molecules targeted against one of these kinases can block the growth of M. tuberculosis within macrophages and thus can be used as novel anti-TB therapy. Using proteomics and global kinome analysis Prof. Av-Gay and his team showed that mycobacterial infection triggers a signaling cascade leading to activation of stress-activated protein kinases. More recently, his research identified an M. tuberculosis Phosphatase, PtpA, which inhibits macrophage “normal” response to infection by targeting host signaling proteins and the macrophage acidification machinery. To show that they used gene knock-out and substrate trapping technologies and a novel technique, neutralizing PtpA in vivo by expressing intracellular single chain antibodies within the TB infected macrophage.
Prof. Av-Gay Collaborates actively with GlaxoSmithKline aiming to identify better Drugs against Intracellular Mycobacterium tuberculosis through the Tres Cantos Open Lab in Madrid Spain (http://www.openlabfoundation.org/). Prof. Av-Gay research into nitric oxide reveal its role in activating M. tuberculosis kinases and identified the thiol-based mechanism used by mycobacteria to protect themselves from nitric oxide damage. Prof. Av-Gay translated his basic research into commercialization by licensing his technologies to various companies. He founded two biotech companies; Enox Biopharma Inc., an emerging medical device company that uses nitric oxide as an antimicrobial agent embedded into Medical Devices to prevent hospital acquired infections and AIT Ltd that develops nitric oxide inhalation therapy against infectious and chronic lung diseases.
Prof. Av-Gay authored 91 peer review scientific publications, review articles, book chapters and 15 patents. Prof. Av-Gay is an editor for the Journal of Biological Chemistry, he serves on scientific advisory boards and is a consultant to several Biotech companies and is a member of the scientific review panels of the Canadian Institute of Health Research, the French Agence Nationale de la Recherche, Innovative Medicine Innovations, The UK welcome Trust, US National Institute of Health, and the European Commission FP6 and FP7 programs.
. Host pathogen interactions in TB, The role of Protein kinases and phosphatases of Mycobacterium tuberculosis.
2. Low molecular weight thiols in bacteria
3. Targeting intracellular Mycobacterium tuberculosis for TB drug development.
4. Novel therapies against infectious lung diseases.