Research in our lab covers a broad range of topics unified by a single theme: the evolution of protein synthesis. Through experimental evolution, bioinformatics, biophysics, and structural biology we study protein synthesis machinery in different species to understand how evolution happens in the world that Darwin never saw – the world of proteins and nucleic acids. Currently, our lab is developing three converging research directions.
1. Adaptation to lifestyles
(Parasitism & genome evolution)
The impact of parasitic lifestyles on the evolution of proteins and nucleic acids. Lifestyles define the way we evolve. In the microbial world, the transition from free-living to host-dependent lifestyles (symbiosis or parasitism) causes a dramatic reduction in genome size; in extreme cases, strictly host-dependent organisms may have genomes that are 30-times smaller than the average genome of a free-living species. By studying the protein synthesis machinery of organisms with drastically reduced genomes, we are able to uncover the fundamental principles of how the transition from a free-living lifestyle to parasitism or symbiosis affects the folding, structure, activity, stability, and evolution of proteins and nucleic acids in the cell.
2. Adaptation to drugs
(How we can prevent or reverse drug resistance)
Understanding drug resistance through experimental evolution. Antibiotic resistance frequently evolves through fitness trade-offs, in which the genetic alterations that confer resistance to a drug can also cause growth defects in resistant cells. By using a microfluidics-based system to conduct evolutionary experiments, we are working to demonstrate that antibiotic-resistant cells can be efficiently inhibited by increasing the fitness costs associated with the evolution of drug resistance. Developing this research direction, we aim to elucidate how – by approaching infectious disease as an evolutionary process – we can attenuate, prevent, or even reverse the evolution of antibiotic resistance in microbial pathogens and cancer cells.
3. Adaptation to new environments
(Protein synthesis at extreme conditions)
Understanding the origin of life through studies of protein synthesis machinery. Ever since the pioneering studies by Carl Woese in the late 1970s, components of the protein synthesis machinery (including rRNA and ribosomal proteins) have been extensively used as the primary tool with which to explore evolutionary relationships between species. Ribosomal RNA, for instance, has been used as a life’s timekeeper to predict when species have diverged from each other and where they belong on the tree of life. We are currently working to show that – through high-throughput structural bioinformatics of ribosomal components – we can learn how to “read” the information that is written within the structures of ribosomes. Our ongoing project shows that by studying changes in ribosome structure between species, we can accurately predict the optimal growth conditions for a given species and gain insights into atmospheric changes that occurred in the distant past.