Projects_laboratory_m

Microbiome-Mediated Interactions in Atherosclerosis: SESN and APO Families' Proteins, Cytokines, and Clinical Manifestations

Project goal: To identify new biomarkers of atherosclerosis based on the study of the oral cavity and gut microbiome, the immunological profile, clinical manifestations, and specific proteins of the APO and SESN
families.
Project description: Main concept of this project includes oral and gut microbiome study, and its metabolic pathways in patients with coronary AS in association with specific proteins APO and SESN, cytokine profile and clinical indicators. Multidisciplinary nature of study brings together experts from various scientific fields of medicine, biology, biotechnology, bioinformatics, immunology, allows a deeper understanding of complex relationships in AS pathogenesis. This approach will contribute to disclosure of new pathways and factors affecting AS development and progression and is aimed at finding new potential biomarkers.
Project facilitators:
PI: Argul Issilbayeva
Samat Kozhakhmetov
Laura Chulenbayeva
Madiyar Nurgaziyev
Zharkyn Jarmukhanov
Symbat Seidulla
Bayan Ainabekova
Assel Meiramova
Yelena Rib


Project partners:
Heart Center: UMC
Realisation period:
2024-2026
Expected results: - at least 3 (three) articles and (or) reviews in peer-reviewed scientific publications in the scientific direction of the project, indexed in the Science Citation Index Expanded and included in the 1st (first), 2nd (second) and (or) 3rd (third) quartile by impact factor in the Web of Science database and (or) having a CiteScore percentile in Scopus database of at least 60 (sixty);
- at least 1 (one) article or review in a peer-reviewed foreign or domestic publication recommended by the KOKSNVO;
- or at least 2 (two) articles and (or) reviews in peer-reviewed scientific publications indexed in the Science Citation Index Expanded and included in the 1st (first) and (or) 2nd (second) quartile by impact factor in the Web of Science database and (or) having a CiteScore percentile in the Scopus database of at least 70 (seventy);
- or at least 1 (one) article or review in a peer-reviewed scientific publication indexed in the Science Citation Index Expanded and included in the 1st (first) quartile in the Web of Science database or having a CiteScore percentile in the Scopus database of at least 90 (ninety).
Absence of such studies in the World increases scientific, technical effect of project results. In future it will lead to effective AS prevention, diagnosis, treatment methods development, reduction of socio-economic burden of state. Multiplicative nature of results is due to wide scope of application, demand from AS patients, individuals with increased AS development: smokers, hypertension, diabetes, hypercholesterolemia, etc.Target consumers, application scope are medical institutions, patients with coronary AS, their families, pharmaceutical companies, public, private scientific organizations. Applicability, possibility of commercialization of obtained scientific results: project results can be applied in development of new AS diagnostic methods, early detection, prevention. Results will also contribute to new treatment methods development, focused on new AS biomarkers, will have commercial potential in market of medical technologies, pharmacological industry. Impact of expected results on development of life and health sciences, related fields of science and technology will be significant and is due to creation of foundation for future research in life sciences, will strengthen scientific and technical potential of Kazakhstan, increase competitiveness, strengthen our country position in world scientific community.
Methodology:Our study investigates the relationship between coronary atherosclerosis and microbiome composition in patients aged 40-80 years with >50% coronary occlusion compared to healthy controls. Research is conducted in Astana following ethical principles (Helsinki Declaration) and approved by Nazarbayev University Ethics Committee. Participants undergo cardiological and dental examinations, with blood tests, oral cavity swabs, and fecal samples collected for analysis. The oral microbiome is studied via 16S rRNA gene sequencing, while gut microbiome is analyzed using Shotgun metagenomic sequencing on the Illumina NovaSeq 6000 platform. DNA extraction is conducted using ZymoBIOMICS DNA Miniprep Kit, following the manufacturer's recommended protocol. DNA quality and concentration are assessed using multiple methods: spectrophotometric analysis with NanoDrop 2000 (Thermo Scientific), fluorometric quantification using Qubit 3.0 Fluorimeter, and integrity verification through agarose gel electrophoresis. Raw sequencing data undergo rigorous quality control and preprocessing. Adapter sequences and low-quality reads are removed using Trimmomatic (version 0.39). Quality-filtered reads are assembled and annotated using multiple computational approaches. MetaPhlAn 4 is employed for taxonomic profiling, while HUMAnH 3 performs functional annotation using the UniRef90 database. Additionally, we examine inflammatory markers, apolipoproteins, and SESN proteins using Luminex Flexmap 3D and ELISA methods. Data analysis employs R v4.4.1 and Python v3.9.14 software.
Contacts: argul.issilbayeva@nu.edu.kz