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Molecular Chaperones and Immunology

#0091


Design of recombinant protein-peptide immunomodulators using new basic molecular biology data.

Tech Area / Field

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

Status
8 Project completed

Registration date
13.09.1993

Completion date
14.07.1998

Senior Project Manager
Kondratenkov Yu B

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

Collaborators

  • University of Turku / Finnish-Russian Joint Biotechnology Laboratory, Finland, Turku\nUniversity of Medicine and Dentistry of New Jersey (UMD) / Robert Wood Johnson Medical School, USA, NJ, Piscataway\nUniversity of Turku, Finland, Turku\nInstitute of Animal Health, UK, Compton\nDon & Sybil Harrington Cancer Center / Department of Immunologycal and Macromolecular Crystallography, USA, TX, Amarillo\nUniversity of Birmingham / Department of Immunology, UK, Birmingham\nUniversity of Reading, UK, Reading

Project summary

In the recent years the investigations in the fields of molecular biology and immunology allowed one to specify problems the solution of which is critical for further development of the sciences. Among these problems, one of the most vital is the problem of molecular chaperone functions as an intracellular immune system, its evolutionary and structure-function relationship with classic immune system. The importance of the problem lies in the fact that its solution would provide a clue to mechanisms of induction of immunologic tolerance and immunosuppression, as well as to mechanisms of immunity overcoming by pathogenic bacteria.

The knowledge about molecular chaperones acting as an intracellular immune system inherent to all cell organisms, including prokaryotes, is underlying the project.

The aim of the project is to study mechanisms of functions of the system of molecular chaperones and related proteins as an intracellular immune system, using for illustration gram-negative bacteria, as well as the interaction of molecular components of the system with classic immune system of mammals, and to demonstrate the potential of application of the data of basic research to design recombinant and synthetic protein-peptide immunomodulators.

Major research tasks to solve the problem specified:

- to design recombinant strains producing proteins of Y. pestis f1 operon required for basic research under the project;

- to study and compare structural and functional properties of periplasmic molecular chaperones Caf1M, small heat shock proteins (sHsp25, sHsp27) and IgG as evolutionary related proteins belonging to an immunoglobulin superfamily;

- to study and compare structural and functional properties of Y. pestis F1 antigen and IL-1 as proteins sharing evolutionary structure-function relationship;

- to elucidate mechanisms of the interaction of IL-1 with E. coli cells transformed by f1 operon, and the role of molecular usher protein Caf1A and molecular chaperone Caf1M in the given process, and to study biologic effects induced in E. coil cells following the interaction with IL-1;

- to demonstrate the potential of application of basic molecular biology data for designing of synthetic and recombinant protein-peptide immunomodulators, including the proteins derived from f1 and pH6 operons of Y. pestis. Scientific novelty of the studies to be performed lies in the fact that molecular chaperones will be studied for the first time as the system acting as intracellular immune system, an evolutionary precursor of the classic immune system of mammals.

Under the project new data will be obtained: about mechanisms of molecular chaperone functions as intracelllular immunity system; about the interaction between molecular chaperone system and immune system; about immunity evolution.

The role of F1 and pH6 antigens in the pathogenesis of plague and immunity suppression at early stages of the infectious process will be elucidated.

Using f1 operon, strains overproducing biologically active substances (cytokines, antigens, etc.) intended for medicine and veterinary medicine, will be designed.

The recombinant E. coli strains obtained under the project will be of commercial significance as producers of F1 antigen and periplasmic molecular chaperone Caf1M of Y. pestis, and synthetic peptides derived from immunoglobulins and cytokines will be of commercial value as basic components of pharmaceuticals.

It is anticipated to employ in the work different physical methods, including microcalorimetry, radio receptor binding assay, authors' modifications of the theoretical conformation analyses, and molecular biology, biochemical, pharmacological and immunological methods.

The implementation of the project will significantly contribute to the development of basic and applied biology and medicine, as well as facilitate the solution of one of social problems, namely: it will provide to scientists and engineers of the Institute of Immunology of State Concern "Biopreparation" engaged previously in the studies carried out to order of the Ministry of Defense, the opportunity to redirect their scientific interests, and to apply the experience acquired to conduct basic and applied research related to peaceful international science and technology problems in the fields of biology and medicine, to develop long-term prospects for fruitful cooperation within the international scientific community.


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