Institute of Microbial Technology,
Sector 39-A, Chandigarh
E-mail: firstname.lastname@example.org; email@example.com
Phone No: 0172-2636680-94 ext: 3293
Write-up of research and development interests/focus, past and present goals:
Current Research and Interests:
Virulence of Mycobacteria is a multifaceted phenomenon based on the expression of multiple genes involved in various stages of host-pathogen interactions including adhesion, invasion, intracellular replication and dissemination to other sites. Although both virulent and avirulent mycobacteria are internalized by monocytes and macrophages, only pathogenic mycobacteria survive and replicate intracellularly. This intracellular pathogen can successfully survive inside the host macrophages inspite of the antimicrobial effector functions of the macrophages. Its survival during phagocytosis and its subsequent multiplication within these professional phagocytes are critical to its pathogenesis. A variety of mechanisms have been suggested to contribute to the survival of M. tuberculosis within macrophages, including inhibition of phagosome-lysosome fusion, inhibition of the acidification of phagosomes, resistance to killing by reactive oxygen and nitrogen intermediates, and modification of the lipid composition of the mycobacterial cell membrane, thereby altering its capacity to interact with immune or inflammatory cells.
After completion of genome sequence of M. tuberculosis, additional genes and protein products of the pathogen have been identified as potential antigens playing roles in pathogenesis. There is a differential expression of proteins during infection of human macrophages. Expression of some of these proteins within macrophage leads to enhanced survival and/or increased virulence of mycobacterium within macrophages.
Although, there are some evidences accumulating in the literature for the modulation of macrophage cell signaling upon mycobacterium infection, however, very little is known about the pathogen-host interactions that orchestrate this complex program. So far the major thrust is given to understand the alteration in the immune responses of the host by mycobacterium. A key question in studies of these cascades is how mycobacterium enables itself to evade the defence surveillance of host. Not much work is done to understand about those proteins of the pathogen that are exactly responsible to mount such a camouflage response upon uptake by macrophages. Modulation of macrophage cell signaling by mycobacterial infection may imply that direct protein-protein interactions between pathogen and host could be one of the most probable factors to determine the protective immune response.
Our main aim is to search for interacting partners of proteins that lead to enhanced survival and/or increased virulence in macrophages using yeast two-hybrid system. These proteins will be used as bait while the macrophage library will serve as prey. With the help of Bioinformatics, these interacting partners will be judged for their homology, followed by functions and ultimately they will be placed in their corresponding array of regulatory pathways. Probable protein interactions picked up in experimental screening of Y2H will be confirmed later by various cell biological techniques namely co-immunoprecipitations, localizations etc.
Besides this, presently we are engaged in studying the interaction of Mycobacterium with their hosts. When a pathogen invades in a host, it engages the host’s cell in a two-way biochemical interaction, or cross talk. This cross talk leads to responses from both the bacteria and the host’s cell. These responses are dependent on the type of infected cell and induced changes in the hosts cell plasma membrane, and profound cytoskeleton rearrangements, which ultimately leads to bacterial internalization. The activity of MAP Kinase pathway is one of the key components that are affected by this whole process. We studied the effect of Eis protein (protein responsible for enhanced intracellular survival) on signaling of the host. We found that recombinant Eis protein disturbs the cross regulation of T-cells and it modulates the MAPK pathway and subsequent release of cytokines like TNF-α, IFN-γ, IL-4 and IL-10 etc.