Angad P. Mehta

1. Platforms to combat emerging pathogens: (A) Targeting RNA capping enzymes from emerging pathogenic 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. (B) Antibody engineering and evolution to target zoonotic pathogens: We are developing novel platform for evolving antibodies targeting emerging zoonotic viruses. We seek to mechanistically understand how animal antibodies are involved in controlling viral transmission. These mechanistic studies provide us with a foundation to develop and evolve novel human antibodies that have broad neutralization potential against emerging zoonotic pathogens. Such antibody engineering and evolution platforms are expected to provide a foundation for developing human antibodies targeting epitopes on viruses, drug resistant bacteria and cancer.

2. 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.

3. Engineering selectivity in targeting cancer: We are combining our expertise in synthetic biology and synthetic chemistry to develop fundamentally novel, modular platforms to engineer selectivity in targeting cancers. We are using principles of directed evolution and biomolecule delivery platforms to engineer novel biologics that specifically target cancers where the biomarkers are well characterized.