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Molecular and immunopathogenesis mechanisms of oral commensal streptococci induced cardiovascular disease infective endocarditisct"
Taiwan (FMS-Taiwan) - National Taiwan University, Taipei
COLLEGE OF MEDICINE GRADUATE INSTITUTE OF IMMUNOLOGY
Type of Research Project
- Basic science
What is the background of the project?
The immune-enhancing and immunothrombosis roles of neutrophil extracellular traps (NETs) in the progression of immune-related or thrombosis-related diseases such as autoimmune diseases, tumor and cardiovascular diseases have been highlighted recently. Infective endocarditis (IE) is a typical biofilmrelated life-threatening infectious disease on the heart valves. Histopathologically, IE is characterized by the formation of vegetations, fibrin-platelet clots with the embedded bacteria forming biofilm, which is refractory to routine antibiotic treatment. Using Streptococcus mutans-induced IE model, our pioneering results lead to the notion that host factors play important roles in the pathogenesis of IE. Specifically, platelet is an essential host factor for IE pathogen to enhance bacterial biofilm formation and resistance (J Infect Dis. 2012; 205:1066-75), and the bacteria-activated platelets can further induce NET release to induce more platelet aggregation, fibrin-clot formation and vegetation expansion (Circulation. 2015; 131:571-81; Thromb Haemost. 2019; 119:786-796). The mechanisms of NET induction are quite complex, involved ROS production, granule protein translocation, autophagy activation and histone citrullination and vary depending on the source of NET stimuli.
What is the aim of the project?
The specific aims of this project are: 1.Elucidation of the molecular mechanisms of platelet-dependent S. mutans induced NETosis. 2.Investigation of signaling pathway of P-selectin expression on S. mutans activated platelets. 3.Elucidation of the molecular mechanisms of platelet-independent S. mutans induced NETosis. 4.Identification of specific plasma component(s) that contribute to S. mutans induced NETosis 5.Investigation of and mechanisms of the identified plasma component(s) in the NET induction and the roles in disease progression
What techniques and methods are used?
What techniques and methods will be used? We will use basic genetic, biochemical, and molecular biological approaches to analyze these genes, such as genetic screening, molecular cloning, protein analysis, RNA interference, etc. We will also use advanced microscopy techniques to dissect the function of these genes, such as fluorescence microscopy, confocal micrscopy and twophoton microscopy. Our lab is equipped with all necessary equipments for these studies. Will there be any theoretical teaching provided (preliminary readings, lectures, courses, seminars etc)? Yes. We will have courses on microscopy and brain development. Literature in the related field will also be assigned to catch up with recent progress.
What is the role of the student?
- The student will observe the practical experiments but will be highly involved in the analysis of the results
- The tasks of the student will be performed on his/her own
- The tasks will be done under supervision
What are the tasks expected to be accomplished by the student?
The student will learn new techniques from the laboratory and (hopefully) enjoy the process of scientific discoveries. When performing experiments, the student is expected to follow the lab safety rules. If animal handling is needed for the project, the student is required to complete the animal handling training and follow all rules and protocols established by the Institutional Animal Care and Use Committee (IACUC). When the student is not in the lab, trying as many different Taiwanese cuisines is highly recommended.
Will there be any theoretical teaching provided (preliminary readings, lectures, courses, seminars etc)
Animal experiment courses Lab meeting
What is expected from the student at the end of the research exchange? What will be the general outcome of the student?
- The student will prepare a scientific report - No specific outcome is expected
What skills are required of the student? Is there any special knowledge or a certain level of studies needed?
Basic concepts on biology, chemistry, or physics are required. Experience in hands-on laboratory work is preferred. Dare to try all kinds of food is a must. For more information, please go to: http://immunology.eday.com.tw/
Are there any legal limitations in the student’s involvement
Type of students accepted
This project accepts: - Medical students - Graduated students (less than 6 months)
- Neutrophil extracellular traps enhance Staphylococcus aureus vegetation formation through interaction with platelets in infective endocarditis. Thromb Haemost. 2019 May; 119(5):786-796. doi: 10.1055/s-0039-1678665. Epub 2019 Feb 7. Hsu CC; Hsu RB; Ohniwa RL; Chen JW; Yuan CT; Chia JS; Jung CJ. https://www.thieme-connect.com/products/ejournals/abstract/10.1055/s-0039-1678665
- Endocarditis pathogen promotes vegetation formation by inducing intravascular neutrophil extracellular traps through activated platelets. Circulation. 2015 Feb 10; 131(6):571-81. doi: 10.1161/CIRCULATIONAHA.114.011432. Epub 2014 Dec 19. Jung CJ; Yeh CY; Hsu RB; Lee CM; Shun CT; Chia JS. https://www.ahajournals.org/doi/full/10.1161/CIRCULATIONAHA.114.011432?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub%3Dpubmed&
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