Department of Chemistry and Chemical Biology
Experimental molecular evolution
In recent work done in the lab, fitness of E. coli strains were determined with chromosomally incorporated mutations in the folA gene that render Dihydrofolate Reductase (DHFR) aggregation-prone (see this article). It showed that cells carrying an aggregation prone mutant of DHFR show an elongated morphology. Though preliminary experiments showed that this might be a result of thymine limitation due to loss of DHFR function, certain other experiments suggest that the this particular phenotype is different from those of DHFR inhibition using specific drugs. We therefore would like to explore whether this particular phenotype is due to any new protein-protein interaction network created by an aggregated form of DHFR or simply a result of non-specific toxicity. This would also shed light on why protein aggregation is so detrimental to organismal fitness.
In other work, we are trying to gather a comparative understanding of the relationship between protein folding and organismal fitness in prokaryotic and eukaryotic systems. The role of the protein quality control machinery in shaping this fitness landscape is also an area of substantial interest.