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Alexander (Shura) Mankin


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 most antibiotics are unclear. We are trying to uncover the principles of action of ribosome-targeting antibiotics and pave new venues for developing better drugs. In parallel, we are investigating molecular mechanisms of antibiotic resistance and principles of regulation of antibiotic resistance genes.


3. Mechanisms of antibiotic resistance
     Antibiotic resistance is an important medical and biological problem. Some antibiotic genes have been evolutionary optimized to be expressed only when the antibiotic is present. Regulation of expression of such genes is often controlled by programmed translation arrest. We are exploring the molecular mechanisms of antibiotic- and nascent peptide-controlled arrest of translation and its role in the regulation of inducible antibiotic resistance genes.


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

We collaborate with the laboratories of:
- Dr. Daniel Wilson (Ludwig-Maximilians-Universitat Munchen, Germany)
- Dr. Tanel Tenson (University of Tartu, Estonia)
- Dr. Ronald Micura (Center for Molecular Biosciences, Innsbruck, Austria)
- Dr. Axel Innis (Institut Europeen de Chimie et Biologie, Bordeaux, France)
- Dr. David Sherman (University of Michigan, Ann Arbor, USA)
- Dr. Petr Sergiev (Moscow State University, Russia)
- Dr. Michael Jewett (Northwestern University, Evanston, USA)