Structure and dynamics of RNA
We work at the interface of several disciplines. Our current work focuses on the study of protein synthesis by molecular and structural approaches with new developments in nanotechnology.
RNA has been shown to be an excellent drug target. Our group is interested in studying the role of RNA in biological processes and how activity can be targeted by drugs. We use tools of microbiology, chemistry, biochemistry, omics and fluorescence microscopy. We focus on a family of antibiotics, aminoglycosides, that bind RNA and affect translation with lethal consequences for the cell. Our work links RNA, antibiotics with novel therapeutic strategies that target multidrug resistant pathogens and persister cells.
Antibiotic uptake at the single-cell level
To reach their cellular targets, many antibiotics must cross bacterial membranes. For aminoglycoside antibiotics, the detailed mechanism of entrance remains an intense area of focus. We are investigating the mechanism of uptake of aminoglycosides by bacteria and how these antibiotics interact with cell membranes. We have developed active fluorescent derivatives of aminoglycosides and methods for accurately monitoring uptake by bacteria. Our recent work showed that when used with adequate protocols, these derivatives allow single-cell analysis of aminoglycoside uptake by fluorescence microscopy and fluorescence activated cell sorting.
Robust characterization of the drug uptake using neomycin coupled to non-permeable cyanine dyes
Antibiotic-based novel therapeutic strategies
In addition to studying how this type of drugs accumulates in bacteria, we use aminoglycoside templates to develop novel drugs with superior activity against pathogens. We are investigating solutions to produce derivatives that are strongly active in killing multidrug resistant pathogens and persister cells from the ESKAPE group.
The aminoglycoside neomycin bound to its ribosomal RNA bindings sites.
RNA structural elements and recoding
We have a longstanding interest in mechanisms of translation that are modulated by RNA structures or modifications such as in translational recoding, -1 frameshifting or selenocysteine incorporation. We have used tools of structural biology and biochemistry to characterize RNA conformational changes in hairpins or pseudoknots when these structures meet the ribosomal helicase center. We are currently exploring how viral RNA pseudoknots can be targeted by drugs.
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