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Biological Physics (iPoLS) Seminar: Angad Mehta (UIUC) "Synthetic Biology Platforms for Evolutionary Studies and Human Health"

Event Type
Department of Physics
Loomis Lab 144
Apr 1, 2022   2:00 pm  
Angad Mehta (UIUC)
Brandy Koebbe
Originating Calendar
Physics - Biological Physics (CPLC/iPoLS) Seminar

In this talk, I will discuss our investigations into two key areas of research: (i) engineering synthetic endosymbiosis to study organelle evolution and develop synthetic biology platforms, and (ii) engineering synthetic platforms 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 bacterial endosymbionts actually 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 tackle pathogenic RNA viruses. We have developed a phenotypic yeast and pseudoviral platform to understand the molecular details of these essential viral RNA capping 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.

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