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Invited researcher Seamus Martin
Contract number
14.B25.31.0013
Time span of the project
2013-2017

As of 30.01.2020

16
Number of staff members
16
scientific publications
8
Objects of intellectual property
General information

Name of the project: Search for low-molecular inhibitors of cell proteases responsible for processing and activation of IL-36 cytokines during inflammation

Strategy for Scientific and Technological Development Priority Level: в


Goals and objectives

Research directions: Biotechnologies

Project objective: Research of IL-36 proteins, finding low molecular inhibitors of proteases participating in processing and activation of IL-36 as a possible therapy for inflammatory diseases, assessment of efficiency of potential inhibitors in model mice, creation of medications for treatment of inflammatory skin diseases.


The practical value of the study

  • The Laboratory has researched activity of low-molecular inhibitors of proteolysis of IL-36 on cell cultures.
  • A set of optimized inhibitors has been developed.
  • We have investigated activity of low-molecular inhibitors on animal models of psoriasis.
  • New data have been obtained on activation of recombinant interleukins IL-36 by caspase-3. The data confirm the hypothesis that IL-36 proteins can be selectively activated through internal proteolytic processing.
  • We have detected a set of inhibitors that efficiently suppresses proteolysis of synthetic substrates and signaling of IL-36 in the cellular system.

Implemented results of research: A method has been created for producing degranulate and in vitro testing based on it. The method has found practical applications at the Department of Skin and Sexually transmitted Disease of the S.M. Kirov Military Medical Academy

Education and career development:

  • 4 candidate dissertations have been defended.
  • Lecture courses in biotechnologies for bachelors and masters.
  • Internships have been organized on the grounds of the Laboratory for students and postgraduates.

Organizational and structural changes: The scientific and educational enter «Medical biotechnologies» has been created.

Other results: The leading scientist Seamus Martin co-authored the 11th, 12th and 13th editions of «Essential Immunology», the main textbook in immunology.

Collaborations:

  • Trinity College (Ireland): joint research, student exchange, organizing seminars and conferences
  • University of Rome Tor Vergata (Italy): student exchange, organizing seminars and conferences
  • Saint Petersburg Institute of Pharmacy CJSC (Russia), Research Institute of Hygiene, Professional Pathology and Ecology of the Federal Biomedical Agency of the Russian Federation (Russia), S.M. Kirov Military Medical Academy (Russia): joint research

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Sullivan G.P., Henry C.M., Clancy D.M., Mametnabiev T, Belotcerkovskaya E., Davidovich P., Sura-Trueba S., Garabadzhiu A.V., Martin S.J.
Suppressing IL-36-driven Inflammation Using Peptide Pseudosubstrates for Neutrophil Proteases. Cell Death & Disease 9(3): 378 (2018).
Sullivan G.P., Davidovich P.B., Sura-Trueba S., Belotcerkovskaya E., Henry C.M., Clancy D.M., Zinoveva A., Mametnabiev T., Garabadzhiu A.V., Martin S.J.
Identification of small-molecule elastase inhibitors as antagonists of IL-36 cytokine activation. FEBS Open Bio 8 (2018).
Smirnov A.S., Nikolaev D.N., Gurzhiy V.V., Smirnov S.N., Suslonov V.S., Garabadzhiu A.V., Davidovich P.B.
Conformational Stabilization of Isatin Schiff Bases – Biologically Active Chemical Probes. RSC Advances 7(17): 10070–10073 (2017).
Clancy D.M., Henry C.M., Davidovich P.B., Sullivan G.P., Belotcerkovskaya E., Martin S.J.
Production of Biologically Active IL-36 Family Cytokines through Insertion of N-terminal Caspase Cleavage Motifs. FEBS Open Bio 6(4) (2016).
Davidovich P., Kearney C.J., Martin S.J.
Inflammatory outcomes of apoptosis, necrosis and necroptosis. Biological Chemistry 395(10) (2014).
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