The increasing occurrence of bacterial resistance to antibiotics ranks
among the greatest threats currently facing human health. The severity
of the situation is such that it is propelling the search for new and
more effective therapeutics.
Antibiotics inhibit bacterial growth by targeting
essential cellular processes such as cell wall synthesis, DNA
replication/transcription and protein synthesis. Protein synthesis is
mediated by a large macromolecular machine, called
the ribosome. Nowadays, more than half of clinically
relevant antibiotics cure infections by binding and inhibiting the
bacterial ribosome, making the ribosome a validated drug target in the
cell.
The fast up rise of drug-resistant
pathogens and the threat that it poses to humanity
warrant the pressing need to bring to the market new and improved
compounds that target the bacterial ribosome. Over the past fifteen
years, high-resolution structures of the ribosome
have been determined at several points along the
translation pathway, providing insights into decoding, translocation,
termination, and the mechanisms by which many antibiotics inhibit
protein synthesis. We are interested in understanding
the mechanisms of protein synthesis and the basic
cellular processes regulating translation by elucidating atomic
structures of ribosome, RNA and protein functional complexes.
One
of the ongoing projects in our laboratory
focuses on the molecular mechanisms by which
bacterial pathogens gain resistance to ribosome-targeting antibiotics.
Of particular interest are the ribosome rescue factors that bind
antibiotic-stalled ribosomes and allow pathogenic
bacteria to resume protein synthesis and thrive in
the presence of drugs. We seek to obtain tri-dimensional complex
structures of the ribosome bound to specialized rescue factors, which
will extend our current understanding of the
molecular mechanisms that contribute to antibiotic
resistance against ribosome-targeting antibiotics in many human
pathogens. The availability of high-resolution structures is expected to
assist in the design of smarter drugs capable
of fighting antibiotic resistance. To achieve these
goals, we are using an integrated approach combining biochemical,
biophysical, genomic, molecular genetics and structure determination
techniques.
We are always looking
for highly motivated individuals who are interested in joining our dynamic and fast growing research group.