Projects

Vladan Čokić, Olivera Mitrović Ajtić, Dragoslava Đikić, Teodora Dragojević, Tijana Subotički, Milica Vukotić

Institute for Medical Research, National Institute for Medical Research, University of Belgrade

In order to discover the mechanism underlying frequent thrombosis in hematologic malignancies, it will be initiated the inflammation dependent activation and interplay of endothelial cells, platelets, and leukocytes with subsequent formation of microparticles and nitric oxide (NO) linked to thrombus generation by induction of coagulation and fibrinolysis. Cancer-associated thrombosis (CAT) is the second leading cause of death in cancer patients including both venous and arterial thromboembolism. While CAT can be treated with anticoagulants, benefits of therapy must be balanced with the increased bleeding risks. The coagulation related cells and biomarkers will be analyzed and selected by flow cytometry from the following hematologic malignancies: multiple myeloma, lymphoma, acute myeloid leukemia, and transplanted patients with graft-versus-host disease (GvHD). Besides clinical follow-up of the patients, extensive preclinical studies will be performed using in vitro cell cultures (hypoxia chamber, RT-qPCR, immunoassays), in vivo mouse models (NO analyzer), and in silico profiling. Activation of the coagulation factors will be observed through the prothrombotic properties of endothelium (microchip flow-chamber system), neutrophil extracellular traps (NETs, spectrophotometry) and anticancer treatments. The proposed study will show inflammatory stimulation of hypercoagulability, chemotaxis of immune response, and NET formation as well as modulation of fibrinolytic system and miRNA regulated platelet activation. In addition, the equilibrium between NO production and oxygen tension will largely influence the inflammation-dependent thrombus formation, with a prognostic significance of hypoxia related gene signature. Understanding the principal mechanisms may allow the development of new therapies to safely prevent CAT in the hematologic malignancies and GvHD, while determination of the specific biomarkers in each malignancy can be used as predictors of thrombosis.

PI Vladan Čokić, P2 Juan F. Santibanez, P3 Olivera Mitrović Ajtić, P4 Milica Vukotić, P5 Dragoslava Đikić, P6 Tijana Subotički, P7 Teodora Dragojević

Severe acute coronavirus virus syndrome 2 (SARS-CoV-2)-induced hyperinflammation is a major reason for severe clinical outcome of coronavirus disease 19 (COVID-19), principally in male patients. Cell entry of SARS-CoV-2 depends on binding to angiotensin-converting enzyme 2 (ACE2) and androgen-regulated transmembrane serine protease 2 (TMPRSS2). We propose a novel androgen-dependent mechanism of ACE2 activation by SARS-CoV-2 in endothelial and immune cells; as well as endothelial dysfunction and hyperinflammation stimulated immune response predispose to thrombus formation in COVID-19. SARS-CoV-2 will be isolated, in vitro expanded, and used to monitor cell signaling and cytokine storm by immune assays and viral load by RT-qPCR. Related androgen pathways will be pharmacologically targeted. Immune-endothelial cell co-cultures will be performed for thrombosis development. We expect androgen-dependent SARS-CoV-2 host cell infection and mediated inflammation in thrombotic complications. This translational research will reveal androgen pathways implication in SARS-CoV-2 infection and therapeutic strategies to speed up patient recovery.

Many organisms, ranging from bacteria and fungi to those much larger animals and plants use chemical and mechanical means to attach permanently or temporarily to surfaces. Some bioadhesives have advantages over synthetic counterparts in terms of their ability to function over a wide temperature range, in wet or dry environments, and to form stable bonds within seconds to all manner of substrata, even those with challenging surface coatings. Knowledge about these materials, in terms of composition, structural design and interactions with surfaces, is necessary to reveal the basic biochemical and mechanical principles involved in biological adhesion. This COST Action will unite the widespread European expertise in the field of biological adhesives (spanning biology, physics, chemistry, and engineering) by streamlining and pooling knowledge, methods and techniques, and will focus activities by avoiding duplication of efforts, decreasing research costs, and accelerating scientific and technological progress in Europe.

Bioaerosols are among the most complex components in the atmosphere. Bioaerosols are relevant as important pathogens in crops and on trees, as aeroallergens in relation to human health and as catalysts for physical processes in relation to climate such as cloud formation processes. The last five to ten years a range of new techniques have become available that enable a number of scientific breakthroughs in the general understanding of bioaerosols and how they interact with the environment. This COST action will establish an interdisciplinary network of experts currently involved in the detection of bioaerosols using both existing methods as well as upcoming technologies such as real or near real-time technologies from atmospheric chemistry and physics or eDNA methods used in molecular biology. A main objective is to critically address the barriers that limits the penetration of new methods in detection of bioaerosols.

Contamination routes of human pathogenic micro-organisms (HPMO) to plants are poorly understood. Basic resources for agro-production, such as soils, water and fertilizers can play a role in contamination of plants, but micro-organisms taxonomical closely related with HPMO are also present plant microbiomes. The HUPLANTcontrol network consists of five working groups: 1) on the ecology of HPMO in plants, 2) on taxonomical identification of HPMO from plants, 3) on characterization of the potential human-threatening nature of HPMOs, 4) on sanitary and agricultural management procedures to control HPMO in plant production facilities and 5) on dissemination of achieved knowledge via connections between science groups and relevant stakeholders from agriculture, industry and public health authorities. The Action integrates molecular biology, bio-informatics, microbiology, ecology, agronomy, veterinary and clinical sciences and places a strong focus on primary plant production, in principle covering all micro-organisms posing potential threats to humans.

Dr Snežana Tomanović, Dr Darko Mihaljica, Dr Ratko Sukara, Dr Gorana Veinović, Dr Valentina Ćirković

Emerging infectious diseases (EIDs) represent a national security threat for every country. The PRAGMATICK COST action aims to disseminate knowledge and promote the application of the Stockholm paradigm in order to anticipate and mitigate disease risk associated with the presence and spread of ticks and tick-borne pathogens (TBPs) under anthropogenic pressure and changing climate. This research network will apply the comprehensive and highly focused DAMA (Document, Assess, Monitor, Act) protocol that allows to “anticipate to mitigate” emerging diseases. The main focus is on urban tick and TBP hotspots and the spread and establishment of ticks and TBPs. PRAGMATICK will find new ticks and tick-borne pathogens before they find us. By applying citizen science and supporting capacity building in the domain of tick and tick-borne disease prevention, the Action will eventually lead to new and improved insights in the potential threats related to this important group of vectors across Europe.