Biology

Dr. Nishad Matange
DST-INSPIRE Faculty Fellow, Department of Biology, IISER Pune

Abstract:

 Evolutionary adaptation is a hallmark of biology, and living organisms are constantly adapting to their environments. These adaptations are mediated by changes in gene sequences, collectively called the ‘genotype’, which alter the properties of the organisms, collectively referred to as the ‘phenotype’. Much of the investment in genome-sequencing technologies and consortia is driven by the idea that understanding genotypes will sufficiently demystify phenotypes. Yet, relationships between genotypes and their phenotypes have proven to be far more complicated than previously imagined. Using bacteria adapting to antibiotics, a well-established experimental paradigm for understanding evolutionary change, I am attempting to de-convolute the relationship between mutations and their phenotypic effects. In this talk, I will describe one of the lines of investigation that my research group has undertaken over the past four years that links mutational-destabilization of proteins during antibiotic resistance evolution with the selection of drug-resistant mutants. I will demonstrate that the phenotypes and fitness effects of mutations that alter susceptibility of Escherichia coli to the antibiotic trimethoprim are highly contingent on genetic backgrounds and environmental parameters like drug concentration. Using these data, I will attempt to draw broader interpretations about how translation of genotypes to phenotypes are confounded and what this means for our understanding of drug resistance evolution in bacteria.