Angad P. Mehta

Strategies to combat emerging RNA viruses: It has become imperative to develop novel therapeutics to tackle emerging RNA virus pathogens including coronaviruses like SARS-CoV-2.​​​​In order to develop novel strategies to combat RNA viruses, we are targeting an essential but relatively less explored target in RNA virus replication , translation and propagation, i.e., viral genome encoded RNA capping enzymes. We are using synthetic approaches to understand the molecular details of these essential viral enzymes. Further we are using a combination of synthetic chemistry and synthetic biology to target these enzymes with a view to develop live attenuated vaccine platforms and antiviral agents. We are expanding this approach to combat existing pathogenic RNA viruses like coronaviruses, Ebola virus and Zika virus, as well as other emerging RNA virus pathogens. 

Strategies to combat drug-resistant bacteria: Antibiotics have been effectively used for decades to treat bacterial infections. However, the emergence of multidrug resistant bacteria has posed a significant challenge to develop new antibiotics. While several ongoing efforts focus on developing new antibiotics, the National Vaccine Advisory Committee has also suggested developing vaccines to combat antibiotic resistant bacteria. To this end, we are developing live attenuated bacterial vaccine candidates by using a combination of small-molecule synthesis, directed evolution and metabolic engineering.

Engineering artificial photosynthetic life-forms for evolutionary studies and synthetic biology: Endosymbiotic theory suggests that mitochondria and chloroplasts evolved from free-living prokaryotes which entered the host cell and were retained as endosymbionts; however, there is a minimal understanding of chloroplast evolved from cyanobacterial endosymbionts. We are developing synthetic model systems to study chloroplast evolution by generating cyanobacterial endosymbionts within eukaryotic cells. Our studies focus on studying various stages of chloroplast evolution including but not limited to (i) cyanobacterial endosymbiont genome minimization, (ii) engineer cyanobacterial endosymbionts to secrete photosynthetic end-products, (iii) develop strategies to facilitate protein exchange between the endosymbiont and host and (iv) mutation-based evolution and selection. These studies are expected to provide molecular details into the evolution of structure/function of complex organelles in eukaryotic cells. Further, these studies are providing us with a roadmap to build synthetic endosymbiotic systems for various synthetic biology applications. Synthetic Biology applications: Engineering genetically tractable yeast/cyanobacteria endosymbiosis will be to generate "photosynthetic yeasts". This platform will couples the biosynthetic and biocatalytic potential of yeast to the photosynthetic ability of cyanobacteria; essentially the cyanobacterial endosymbionts will act as artificial chloroplasts for yeast cells. This platform will allow us harnessing light and photosynthesis to biosynthesize high value molecules like natural products, biofuels among others.