Akademik Veri Yönetim Sistemi
Hasirci V. N. (Yürütücü), Kenar H., Yücel D., Citoğlu S.
Diğer Uluslararası Fon Programları, 2021 - 2024
Covid-19 pandemic highlighted the urgent need for research on infectious respiratory agents to gain more information on risks and outcomes of infection as well as rapid translation of research findings into vaccines or therapeutics to protect the public from a future pandemic. Global health epidemiologists warn that this will not be the last pandemic to affect humans at this level and many international organizations such as Predict Consortium and Global Virome Project have focused on handling future infection waves. This call by Southeast Asia-Europe Joint Funding Scheme is an attempt in this direction to bring scientists from different regions of the world together to fill the knowledge gap in pathogenic processes related to the infection.
Cells in human respiratory tract that express ACE2, the cell surface receptor of SARS-CoV-2 S protein, were identified as the primary target of viral attack and entry, and the most severe clinical phenotypes arise from the infection of alveolar epithelial cells localized on the pulmonary blood-air barrier which are unfortunately difficult to access. The existing cell culture models have so far failed to reconstitute complex lung microenvironment and preclinical animal models do not represent essential properties of human pulmonary blood-air barrier, leading to the need of highly expensive humanized transgenic models. A deeper understanding of infection pathogenesis requires experimental models that can recapitulate essential constituents and microphysiology of pulmonary blood-air barrier.
The study consists of 5 work packages. The hypothesis is that models mimicking pulmonary blood-air barrier can be successfully built using tissue engineered and microfluidic systems, and used to better understand virus-host interactions at the interface. The study includes nanoparticles decorated with ACE2 specific S1 oligopeptides to mimic and compete with the virus in attachment to cells. Another nanoparticle set decorated with S1 and S2 proteins carrying a representative anti-viral agent will be prepared to study the carrier and the drug transport across the barrier. Finally, the results obtained with the nanoparticles will be compared with those obtained with SARS-CoV-2 virus isolate.
MicroLung project is proposed by Indonesia (UGM), Germany (IKTS Fraunhofer) and Turkey (ACU) who are planning to bring together their complementary expertise. During the project, transnational collaboration will be intensive as IKTS, UGM and ACU will exchange nanoparticles, and IKTS and ACU will develop and use the microfluidic (MF) system containing tissue engineered model which will make one of the final pilot level products. In addition, a PhD student from ACU will support the in vitro studies at UGM and exchange expertise in Indonesia for the functionality tests of models using the virus.
The results of the study will benefit not just Covid-19 studies and treatments but will also be applicable to other respiratory viral infection studies.