[EN] Лаборатории

Martin Seamus

Contract number

14.B25.31.0013

Time span of the project

2013-2017

Laboratory's website

As of 30.01.2020

Number of staff members

scientific publications

Objects of intellectual property

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

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 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).

Hosting organization	Field of studies	City	Invited researcher	Time span of the project
Сell Physiology and Pathology Laboratory of Research and Development Center of Biomedical Photonics (10) Orel State University named after I.S. Turgenev - (Orel State University)	Medical biotechnologies	Orel	Abramov Andrey Yuriyevich Russia, United Kingdom	2024-2028
Laboratory for Super-elastic Bio-interfaces Tomsk State University - (TSU)	Medical biotechnologies	Tomsk	Volinsky Alexei Aleksandrovich USA, Russia	2021-2023
Laboratory for Omics Technologies and big data for Personalized Medicine and Health Skolkovo Institute of Science and Technology - (Skoltech)	Medical biotechnologies	Moscow	Borchers Christoph Hermann	2019-2023

Laboratory for Cellular Biotechnology