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Center for Pharmaceutical Biotechnology - m/c 870, University of Illinois at Chicago 900 S Ashland Avenue Chicago IL 60607 Tel: (312) 413-1406 Fax: (312) 413-9303 E-mail: email@example.com
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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
The bacterial ribosome is an excellent antibiotic target. Many antibiotics inhibit the growth of pathogenic bacteria by inhibiting protein synthesis. However, the mechanisms of action of most antibiotics are poorly understood. We are trying to deduce the key principles of action of one of the most important groups of ribosome-targeting antibiotics, macrolides, and pave new venues for developing better antibiotics.
We are looking for new sites of antibiotic action in the ribosome and developing approaches to find new compounds that would selectively inhibit the growth of pathogenic bacteria by acting upon these new antibiotic sites.
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 some of these genes is mediated by interaction of the ribosome with the nascent peptide and with antibiotics. We are exploring the molecular mechanisms of these interactions and their role in the regulation of inducible antibiotic resistance genes.
We are also investigating the genetics, regulation and mechanism of action of an important resistance gene, Cfr, which renders bacteria resistant to many clinically useful antibiotics.
The work in the laboratory is funded by:
Research grants from NIH, NSF, pharmaceutical industry, and international scientific agencies.
We collaborate with the laboratories of:
- Dr. Mandel-Gutfreund (Technion University, Haifa, Israel)
- Dr. Karen Shaw (Trius Therapeutics, San Diego, California)
- Dr. Jamie Cate (University of California, Berkley)
- Dr. Ada Yonath (Weizmann Institute, Israel)
- Dr. Tanel Tenson (University of Tartu, Estonia)
- Dr. Thomas Steitz (Yale University)
- Dr. Zoya Ignatova (University of Potsdam, Germany)