Acharya Narendra Dev College - [ANDC]

In order to promote research amongst various departments, the college has established distinct labs for undertaking research activities by faculty, UG, PG and Ph.D. students. The Research labs are established in the College premises under the direction of one or two faculty members. All the listed faculty members are registered supervisors of the University of Delhi.

In the ‘post-antibiotic era’, where high mortality rates are predicted due to multi-drug resistant (MDR) infections, urgent measures are required to be taken to manage the crisis. Several Mycobacterial spp. are leading pathogens associated with serious infectious diseases (tubercular and non- tubercular). The situation has worsened due to spread of MDR and extremely-drug resistant (XDR) strains, India having second highest MDR-TB burden in the world. Hence, there is pressing need to find alternate solutions and effective strategies to combat the menace of antimicrobial resistance.

In this context, the bactericidal activity of the lytic bacteriophages and their endolysins (and ectolysins) as drugs of bacteriophage origin are gaining attention. This path can lead to discovery of new molecular mechanisms and interactions, which could further pave the way for development of novel therapeutics and also contribute to basic research in the area. Mycobacteriophages infect mycobacterial hosts including fast dividing non-pathogenic M. smegmatis and clinically important M. tuberculosis, M. abscesses among others and are considered as reliable allies against the drug resistant infections. Due to the complex lipid rich cell envelop in mycobacterial species, mycobacteriophages have two different types of endolysins: LysinA and LysinB. The LysinA proteins are highly diverse in sequence and modular in nature. On comparing with standard-of-care antibiotics that often kill bacteria indiscriminately, phage and their derived lysins are not only extremely specific and hence do not harm the normal commensal microflora and they are also potent and effective against drug-resistant strains of pathogens. In my lab in the college, we isolate and purify lytic mycobacteriophages from the local environment using M.smegmatis as the bacterial host. Their morphological, physiological and genomic characterization is carried out to understand their diversity and unique features. We purify phage-derived endolysin enzymes as recombinant proteins and assay them for their biochemical and antibacterial activity.

Drug Discovery: Considering that a multi-target therapy is less likely to be rendered ineffective due to drug resistance than a single target therapy, we are studying Mur ligase (C-F) enzymes from Mycobacterium tuberculosis as the potential multi-targets since they share key structural features and similar catalytic mechanisms. Through Open Source Drug Discovery (OSDD) project on Multi-Target therapy for Tuberculosis, we have developed a One-Pot assay for MurA-MurF enzymes which catalyze the cytoplasmic steps in the peptidoglycan biosynthetic pathway and involve the synthesis of UDP-n-acetylmuramyl pentapeptide, a key precursor molecule required for the formation of the peptidoglycan monomeric building blocks. Through optimization of successive coupled enzyme assays using UDP-n-acetylglucosamine as the initial sugar substrate, we have reconstructed the pathway in vitro. The assay is biochemically characterized for screening of molecules that could disrupt multiple Mur enzymes and has been validated using known furan-based monocarboxylic compounds. Now, using MurB & MurE as the target proteins, in silico screening of FDA approved drugs for Drug Repurposing and anti-tubercular compounds is being done, to be followed by in vitro screening using the assay.

Innovation Project for Colleges Scheme of University of Delhi

Innovation and Entrepreneurship Development Cell, DST, Government of India

Innovation Projects for Colleges Scheme of University of Delhi

Projects Funded by Innovation and Entrepreneurship Development Cell, DST, Government of India