Dissertation defence (Periodontology): MSc Samira Elmanfi

MSc Samira Elmanfi defends the dissertation in Periodontology titled “BACTERIAL SIGNALING MOLECULES AS REGULATORS OF GINGIVAL CELLS’ BEHAVIOR” at the University of Turku on 01 November 2024 at 12.00 (University of Turku, Dentalia, Arje Scheinin Auditorium, Turku).

Opponent: Associate Professor Tülay Yücel-Lindberg (Karolinska Institutet, Sweden)
Custos: Professor Ulvi Gursoy (University of Turku)

Doctoral Dissertation at UTUPub: https://urn.fi/URN:ISBN:978-951-29-9892-0

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Summary of the Doctoral Dissertation:

Cyclic dinucleotides are molecules produced by bacteria that play an important role in regulating various bacterial functions. Host cells recognize these molecules through the stimulator of interferon genes (STING). This detection activates the immune system, leading to the production of interferons and other inflammatory proteins. However, the effects of bacterial cyclic dinucleotides on gingival cells remain unknown.

This PhD research investigates the role of bacterial cyclic dinucleotides and lipopolysaccharides (LPS) of periodontal bacteria (Porphyromonas gingivalis (Pg)) on the cellular response of human gingival cells, specifically keratinocytes and fibroblasts. The study also examines how cyclic dinucleotides activate the STING/TANK-binding kinase1 (TBK1)/interferon regulatory factor 3 (IRF3) pathway in keratinocytes and evaluates their effects on gingival fibroblasts proteome response by using global proteomics analysis, either alone or in combination with Pg LPS.

The results show that cyclic dinucleotides can either increase or decrease the effects of LPS on cytokine production in keratinocytes, depending on the type of cytokine. The STING/TBK1/IRF3 pathway is functional in keratinocytes and is regulated by cyclic dinucleotides. In fibroblasts, cyclic dinucleotides work with Pg LPS to control early cellular responses, while Pg LPS has a greater effect on later responses. Cyclic dinucleotides, alone or combined with Pg LPS, also increase the production of proteins related to immunity and interferon signaling in fibroblasts and other important processes.

This PhD project suggests that bacterial cyclic dinucleotides play an essential role in regulating early cellular responses in periodontal tissue through the STING/TBK1/IRF3 pathway. A deeper understanding of these responses could lead to design cyclic dinucleotide analogs that can function as STING-agonists, antagonists, and potential therapeutics.
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