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.