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Projects / Programmes source: ARIS

Microvesicles as risk factors for secondary thromboembolic events

Research activity

Code Science Field Subfield
3.03.00  Medical sciences  Neurobiology   

Code Science Field
B007  Biomedical sciences  Medicine (human and vertebrates) 

Code Science Field
3.01  Medical and Health Sciences  Basic medicine 
Keywords
Microvesicles, cell membranes, thromboembolisms, cancer, autoimmune diseases
Evaluation (rules)
source: COBISS
Researchers (16)
no. Code Name and surname Research area Role Period No. of publicationsNo. of publications
1.  16104  PhD Apolonija Bedina Zavec  Biotechnology  Researcher  2011 - 2014  154 
2.  36516  Tatjana Blažič    Technical associate  2013 
3.  22482  MSc Goran Bobojević  Computer science and informatics  Researcher  2011 - 2014  12 
4.  33470  PhD Barbara Drašler  Biology  Researcher  2011 - 2014  45 
5.  11155  PhD Damjana Drobne  Biology  Researcher  2011 - 2014  887 
6.  04634  PhD Aleš Iglič  Systems and cybernetics  Researcher  2011 - 2014  975 
7.  13188  PhD Rado Janša  Physics  Researcher  2011 - 2014  200 
8.  05916  PhD Veronika Kralj Iglič  Neurobiology  Head  2011 - 2014  880 
9.  37148  Judita Lea Krek  Neurobiology  Technical associate  2014  18 
10.  19225  PhD Mojca Pavlin  Systems and cybernetics  Researcher  2011 - 2012  264 
11.  36514  Magda Peruško    Technical associate  2013 
12.  30689  PhD Šarka Perutkova  Medical sciences  Beginner researcher  2013 - 2014  54 
13.  36523  Sonja Peternelj    Technical associate  2013 
14.  11949  PhD Borut Štabuc  Oncology  Researcher  2011 - 2014  679 
15.  31673  PhD Roman Štukelj  Sport  Researcher  2011 - 2014  119 
16.  29375  PhD Vid Šuštar  Biochemistry and molecular biology  Researcher  2011 - 2014  75 
Organisations (6)
no. Code Research organisation City Registration number No. of publicationsNo. of publications
1.  0104  National Institute of Chemistry  Ljubljana  5051592000  21,227 
2.  0312  University Medical Centre Ljubljana  Ljubljana  5057272000  77,892 
3.  0381  University of Ljubljana, Faculty of Medicine  Ljubljana  1627066  48,701 
4.  0382  University of Ljubljana, Faculty of Health Sciences  LJUBLJANA  1627155  14,592 
5.  0481  University of Ljubljana, Biotechnical Faculty  Ljubljana  1626914  67,203 
6.  1538  University of Ljubljana, Faculty of Electrical Engineering  Ljubljana  1626965  27,985 
Abstract
Microvesicles are created in the budding process and reflect the composition of the mother cell. They convey matter and information between cells and take part in spreading of inflammation, infection and cancer as well as in thromboembolic disorders secondary to these conditions. Controlled manipulation of the budding process presents a possible mechanism of slowing down the development of some diseases and of decreasing the risk for thromboembolic events while assessment of MVs is a possible method for determination of the risk for thromboembolisms. Understanding of the budding and vesiculation process in vivo and during isolation is yet rudimentary while the existing methods of quantitative assessment of MVs are poorly repeatable and inaccurate and are not yet suitable for use in clinical practice. Preliminary results indicate that a breakthrough to clinically relevant methods is possible only by technological advancement in equipment and a systematic approach to interpretation of clinical studies on large and diverse populations of patients. The scope of the project is improvement of the understanding and assessment of microvesiculation, to render it applicable in clinical practice.    Aims Improvement of the understanding of membrane budding and vesiculation processes and connection of these mechanisms to thromboembolisms Improvement and standardisation of methods for isolation and assessment of MVs Determination of parameters of microvesiculation which are connected to the risk for thromboembolisms, in particular, secondary to cancer and autoimmune diseases, due to side effects of drugs and due to therapeutic procedures Development of simple, low cost, life friendly, clinically relevant diagnostic methods based on characterization of MVs from blood Characterization of substances that would by suppression of microvesiculation act as anticoagulants   Expected results Elucidation of the origin of MVs in blood isolates, improvement of methods for determination of concentration of MVs in isolates, improvement of methods for MV characterization, reflecting an increased risk for thromboembolisms, and determination of natural anticoagulants acting as suppressors of microvesiculation.    Methods Budding and microvesrovesiculation will be considered theoretically and experimentally in artificial membranes and in body fluid samples. In mathematical models we will take into account curvature sorting of membrane constituents and cell deformation due to centrifugation and shear forces in the fluid. Mechanisms of membrane budding will be studied in artificial membranes (phospholipid vesicles) which will be acquired by electroformation. MV will be isolated from body fluids by centrifugation and washing and observed by optical methods and by different microscopic techniques. Proteomic analysis and analysis of the nucleic acid content of MVs will be performed. Quantitative assessment of MVs isolated from blood will be interpreted in the view of clinical status of patients with increased risk for thromboembolisms and of healthy volunteers.     Relevance and potential impact of results Improvement of methods for assessment of risk for thromboembolic events and the corresponding methods for their prevention will have positive medical, ethical, social and economic consequences. Thromboembolisms can cause death or debilitation, decrease the quality of life of patients and their  relatives and present economic burden to society. Determination of substances that suppress microvesiculation and thereby act as anticoagulants will have an impact also on methods for slowing down the spreading of cancer. The proposed project would enable exploitation of the project IMIPEB within the initiative EUREKA, for which Slovenian partners were conditionally granted by MVZT  (the number of the document 430-124/2009/333 from 22.10.2010). The worth of the entire project is around 1M EUR with Slovenian share 450.000 EUR. The coordinator of the project IMIP
Significance for science
In theoretical field, the results contribute to elucidation of interactions in complex systems- In experimental field, the results contribute to elucidation of mechanisms of intercellular communication which are fundamental for functioning of living organisms. In clinical field, the results contribute to implementation of understanding of the above basic processes in diagnostic and therapeutic procedures. The results promote biophysics as a clinically relevant description of the system on the basis of biophysical mechanisms.
Significance for the country
Within the project we collaborated with experts home and abroad and in this way broadend our knowledge. Of particular importance is the fact that, in collaboration with top experts, young associates were able to develop their knowledge. We included into the process of scientific work also undergraduate and graduate students. Three PhD theses were defended and one is in the final stage, of which there are two from the field of medicine and two from the field of nanosciences. Eva Ogorevc continues her work in a renowned research group in Lausanne, Switzerland , Roman Štukelj and Rado Janša are employed in Slovenia. Our contribution has increased the reputation of participant institutions and society in the international scientific and professional community. Particular attention was paid to the ethical aspects of research. We did not perform any experiments that would burden the patients and require life or suffering of animals, nor have we used chemicals obtained by such means. We have strived for development of methods where theoretical biophysics would bear the load and not a repetition of a large number of experiments that cause suffering. In this way we have contributed to raising the quality of life of individuals and society.
Most important scientific results Annual report 2011, 2012, 2013, final report, complete report on dLib.si
Most important socioeconomically and culturally relevant results Annual report 2011, 2012, 2013, final report, complete report on dLib.si
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