Speaker: Angad Mehta, assistant professor of chemistry
Topic: Synthetic Biology for Evolutionary Studies and Human Health
In my lab, evolutionary observations are an inspiration for biological design. In this talk, I will discuss two key areas of research in my lab: (i) directed endosymbiosis to study organelle evolution and develop synthetic biology platforms, and (ii) directed evolution to combat emerging diseases. The first part of my talk is inspired from evolutionary observations that suggests that chloroplasts evolved from cyanobacterial endosymbionts established within eukaryotic cells more than billion years back. This endosymbiotic event led to the origin of photosynthetic eukaryotic life-forms, and drastically impacted global ecology. And yet we have little to no idea of how the bacterial endosymbionts transformed into organelles. These fascinating observations inspired us to develop artificial endosymbiotic platforms between model cyanobacteria and budding yeast (as model host). Particularly, we engineered cyanobacteria to perform chloroplast-like functions for the host yeast cells, where cyanobacteria provide photosynthetically generated ATP and/or assimilated carbon to the host yeast cells and the yeast cells provide essential metabolites to the engineered cyanobacterial endosymbionts. Thorough series of cyanobacterial and yeast engineering efforts we were able to engineer yeast/cyanobacteria chimeras that were able to propagate through at least 15 to 20 generations of growth under optimal photosynthetic growth conditions. Engineered yeast/cyanobacteria chimeras were characterized biochemically and by using a range of microscopy techniques. Using this bottom-up engineering approach we determined critical genetic elements that are necessary to establish synthetic endosymbiosis between cyanobacteria and eukaryotic cells. Such photosynthetic endosymbiotic systems could provide a platform to recapitulate various evolutionary trajectories related to the conversion of photosynthetic endosymbionts into photosynthetic organelles (i.e., chloroplasts), and are therefore, expected to have significant implications on the evolutionary origin of photosynthetic eukaryotic life-forms. Further, we anticipate that genetically tractable photosynthetic platforms, where the endosymbiont provide ATP and assimilated carbon sources by photosynthesis will have significant implications on synthetic biology applications.
In the next part of my talk, I will describe our efforts to use directed evolution experiments to evolve and engineer biologics to tackle pathogenic RNA viruses. We are developing mammalian cell directed evolution platform to evolve and engineer novel antibodies to combat RNA viruses; I will majorly focus on directed evolution platform development. We have also developed phenotypic yeast and pseudoviral platforms to understand the molecular details of these essential viral RNA capping enzymes and evolve and identify low-reversion attenuation mutations in these essential enzymes using directed evolution. Such studies are expected to have an impact on biologics and live attenuated vaccine development.