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Alexander (Shura) Mankin, Nora Vazquez-Laslop
Professor                                    Research Professor


The main areas of research are:

1. Molecular mechanisms of protein synthesis
     The ribosome has the ability to monitor the sequence of the polypeptides it makes. It can recognize and respond to specific nascent peptide sequences. Functional interactions between the ribosome and the nascent peptide are used for the regulation of gene expression and may also facilitate protein folding and targeting.

     We are investigating the molecular mechanisms of nascent peptide-sensing by the ribosome and studying the ribosomal response to regulatory sequences in the nascent peptides.


2. Mechanisms of antibiotic action
     Many antibiotics interfere with the growth of pathogenic bacteria by inhibiting protein synthesis. However, the mechanisms of action of many antibiotics are unknown or unclear. We are studying the sites of binding and mechanisms of action of several new antibiotics. We have recently found that many ribosome-targeting antibiotics inhibit translation in a context-specific manner and arrest translation only at specific mRNA codons. The new genome-wide in vivo approaches and codon-specific in vitro techniques help us understand molecular mechanisms of context-specificity of antibiotic action. We are also exploiting the newly discovered properties of antibiotics to study gene expression and regulation of translation.


3. Ribosome engineering
     Ribosome has evolved to assemble 20 natural amino acids into proteins. The ability to modify and expand the ribosome functionality is one of the main tasks of synthetic biology. We have recently engineered Ribo-T: the ribosome, in which rRNA of the large and small ribosomal subunits are fused into a single molecule and as a result, ribosomal subunits are linked together. We are exploiting the properties of Ribo-T to create an orthogonal translation system in the cell and explore the functions of the ribosome as an RNA-based enzyme.


The work in the laboratory is funded by:
Research grants from NIH, NSF and pharmaceutical industry.

We collaborate with the laboratories of:
- Dr. Yury Polikanov (University of Illinois at Chicago, USA)
- Dr. Michael Jewett (Northwestern University, USA)
- Dr. Jaanus Remme (Tartu University, Estonia)
- Dr. Allen Buskirk (Johns Hopkins University, USA)
- Dr. John Christodoulou (University College London, UK)