We seek to understand the fundamental mechanisms used by Mycobacterium tuberculosis to survive, grow and cause disease. Although our lab uses genetic and biochemical approaches to study this organism, we pursue questions irrespective of the expertise required to answer those questions. This means we will learn approaches/techniques that may be outside of our technical comfort zone. The two major questions we are pursuing are:
‘’’What are the essential components of the peptidoglycan layer and how is the physiology of this layer maintained?’’’ Note that the peptidoglycan layer is an essential ‘organelle’. In 2007, we accidentally identified a transpeptidase that generates mDAP-mDAP or 3→3 transpeptide linkages in the peptidoglycan layer of M. tuberculosis. We are now seeking to comprehensively understand the biology of the peptidoglycan layer. The ultimate aim is to find effective ways to destroy or inhibit biosynthesis of this layer.
What non-coding RNAs exist in M. tuberculosis and what is their relevance to physiology and virulence of this pathogen?’’’ In addition to rRNAs, tRNAs and tmRNA, M. tuberculosis generates a number of other non-coding RNAs. We are studying these RNAs.
- Gupta R, Lavollay M, Mainardi J, Arthur M, Bishai WR, Lamichhane G. The Mycobacterium tuberculosis gene, ldtMt2, encodes a non-classical transpeptidase required for virulence and resistance to amoxicillin. 2010. Nature Medicine. 16, 466-9. PMID:20305661.
- Lamichhane G. Novel targets in M. tuberculosis: search for new drugs. 2010. Trends in Molecular Medicine. PMID: 21071272
- Lamichhane G, Freundlich JS, Ekins S, Wickramaratne N, Nolan ST, Bishai WR. Essential Metabolites of M. tuberculosis and their Mimics. mBio. 2011. 2(1):e00301-10. PMID: 21285434.
- Pelly S, Bishai WR, Lamichhane G. A screen for non-coding RNA in Mycobacterium tuberculosis reveals a cAMP-responsive RNA that is expressed during infection. 2012. Gene. 25;500(1):85-92. PMID 22446041.
- Erdemli SB, Gupta R, Bishai WR, Lamichhane G, Amzel LM, Bianchet MA. Targeting the Cell Wall of Mycobacterium tuberculosis: Structure and Mechanism of LD-transpeptidase 2. 2012. Structure. 20(12): 2013-15. PMID 23103390
- Lamichhane G, Arnvig K, McDonough K. Definition and Annotation of (myco)bacterial non-coding RNA. 2012. Tuberculosis.