Chemistry-Biology Interface Seminar: Dr. Angad Mehta, The Scripps Research Institute (Host: Laura Dassama)
Chemistry-Biology Interface Seminar: Angad Mehta, The Scripps Research Institute (Host: Laura Dassama)
About the Seminar
"Exploring evolution through synthetic approaches"
In this talk, I will discuss our investigations into two key theories of evolution of life: (i) RNA world hypothesis and (ii) Endosymbiotic theory of organelle evolution. Almost five decades ago Rich, Crick, Orgel and others proposed the RNA world hypothesis. Subsequent studies have raised the possibility that RNA might be able to support both genotype and phenotype, and the function of RNA templates has been studied in terms of evolution, replication and catalysis. In our efforts to engineer strains of E. coli in which a large fraction of 2’-deoxycytidine in the genome is substituted with the modified base 5-hydroxymethyl-2’-deoxycytidine, we generated mutant strains of E. coli that showed significant (~40-50%) ribonucleotide content in their genome. We characterized the properties of these chimeric genomes and the corresponding strains to determine the circumstances under which E. coli can incorporate high levels of ribonucleotides into its genome. These studies have potential to investigate various aspects of the hypothesized transition from RNA world to DNA world. In the next part of my talk, I will discuss our synthetic approach to experimentally evolve mitochondria-like organelles in a laboratory setting. The endosymbiotic theory suggests that mitochondria evolved from free-living prokaryotes which entered the host cell and were retained as endosymbionts. We modeled the first stage of the endosymbiotic theory of mitochondrial evolution by engineering endosymbiosis between two genetically tractable model organisms, E. coli and S. cerevisiae. In this model system, we engineered E. coli strains to survive in the yeast cytosol, and provide ATP to a respiration-deficient yeast mutant. In a reciprocal fashion, yeast provided thiamin to an endosymbiotic E. coli thiamin auxotroph. This readily manipulated chimeric system was stable for more than 40 doublings and should allow us to investigate various aspects of the endosymbiotic theory of organelle evolution.
About the Speaker
Angad Mehta did his undergraduate studies at the Institute of Chemical Technology, Mumbai, India. He joined Prof. Tadhg P. Begley’s laboratory at Texas A&M University for his graduate studies. His Ph.D. dissertation focused on mechanistic and structural characterization of radical S-adenosyl methionine enzymes involved in cofactor biosynthesis. One of his thesis projects resulted in the discovery of a pathway involved in the anaerobic biosynthesis of the lower ligand of vitamin B12. Next, he joined Prof. Peter G. Schultz laboratory at The Scripps Research Institute, La Jolla for his postdoctoral studies where he worked on developing synthetic approaches to explore two key theories of evolution: (i) RNA world hypothesis and (ii) Endosymbiotic theory of organelle evolution. These studies resulted in the discovery of bacterial strains containing chimeric DNA-RNA genomes. Dr. Mehta also established an endosymbiotic relationship between two model organisms – S. cerevisiae and E. coli to evolve mitochondria-like organelles in a laboratory setting. Dr. Mehta’s awards include: Sir Ratan Tata Trust Scholarship for Academic Excellence (2006); Young Innovator’s Choice Competition Award (2008); Dow Chemical Scholar Award (2014) among others.