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Molecular Chaperones and Immunity

#0091-2


Design of Recombinant Protein-Peptide Immunomodulators

Tech Area / Field

  • BIO-MIB/Microbiology/Biotechnology
  • BIO-CGM/Cytology, Genetics and Molecular Biology/Biotechnology

Status
3 Approved without Funding

Registration date
20.08.1998

Leading Institute
Institute of Immunological Engineering, Russia, Moscow reg., Lyubuchany

Collaborators

  • University of Reading, UK, Reading\nUniversity of Maryland at Baltimore, USA, MD, Baltimore\nUSAMRIID, USA, MD, Fort Detrick\nUniversity of Birmingham, UK, Birmingham\nMartin-Luther Universität Halle-Wittenberg, Germany, Merseburg\nUniversity of Turku / Finnish-Russian Joint Biotechnology Laboratory, Finland, Turku\nUniversity of Medicine and Dentistry of New Jersey / Robert Wood Johnson Medical School, USA, NJ, Piscataway

Project summary

Studying the molecular mechanisms of the virulence of pathogenic microorganisms, particularly those, which are responsible for their ability to overcome the immunity, is one of the most urgent problems in biology and medicine. It is necessary to solve this problem in order to develop effective means for prevention and treatment of infectious diseases.

The objective of the Project 091-94 extension is to study the chaperone-dependent mechanism of overcoming the immunity by plague agent Yersinia pestis as a way to improve the molecular antiplague vaccine. Besides, using a procedure for designing and selection of randomised single-chained oligonucleotides (aptamers) of DNA or RNA origin (SELEX), the Project executors plan to search for the aptamers capable to selectively block the functions of V protein, key for the virulence of Yersinia and encoded by Yop virulon, for urgent prevention and treatment of yersinioses.

The scientific novelty of the proposed studies is in elucidating the peculiarities of the molecular functioning mechanisms of operons of Gram-negative pathogens (using caf and psa operons of Yersinia pestis as an example) responsible for the formation of virulence-associated surface structures with atypical morphology and influencing the chaperone-dependent mechanism of overcoming the immunity by these pathogens. In particular, some data will be obtained on the interaction of the products of caf and psa expression with the type in secretion system.

To achieve the objectives set in the Project we plan to use a complex of modem research methods, including gene engineering, site-directed mutagenesis, a procedure for designing and selection of randomised single-chained oligonucleotides (aptamers) of DNA or RNA origin (SELEX - Systematic Evolution of Ligands by Exponential enrichment). X-ray analysis, electron microscopy, differential adiabatic scanning microcalorimetry, circular dichroism, spectrofluorimetry, molecular computer modeling, radioreceptor analysis. The biological activity of the mentioned compounds will be studied using a complex of biochemical, immunological and pharmacological methods.

The extension of Project 091-94 will make a significant contribution to the development of fundamental and applied biology and medicine as well as to the solution of a social problem, i.e. it will give the scientist and engineers at the Institute of Immunological Engineering, Joint-Stock Company "Biopreparat", who fulfilled earlier state orders of the Ministry of Defense, an opportunity to apply the accumulated experience and the international relations, they obtained executing Project 091-94, for carrying out fundamental and applied studies, connected with the solution of international research and technical problems in the field of biology and medicine for peaceful purposes, for creating long-term perspectives of fruitful activity within the international scientific community.


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