Periodic Reporting for period 2 - OrganoVIR (Organoids for Virus Research - An innovative training-ETN programme)
Periodo di rendicontazione: 2021-01-01 al 2022-12-31
There are many viral infections that pose a huge burden on human health, for which treatment or vaccines are still not available. OrganoVIR (Organoids for Virus Research) aims to study these viruses with human cell cultures known as organoids, that accurately mimic human tissues. Using these human organoids will increase our understanding of these viral infections, which will help with development of new antiviral treatments or vaccines. OrganoVIR’s goal is to establish human organoids as superior models for viral pathogenesis studies and antiviral testing, thus replacing animal models.
OrganoVIR has attained this goal by achieving its four research objectives: 1) Develop, standardize, and improve organoid models for virus research; 2) Understand human viral pathogenesis by using human organoids as infection models; 3) Apply organoids in antiviral compound testing; and 4) Assess ethical and societal impact of organoid technology and identify factors that drive investment in this new biotechnology.
To accomplish its goals, OrganoVIR has provided an innovative training programme aimed to deliver highly skilled researchers that are capable of implementing and sustaining organoid technology, as well as innovate virus research in the EU. OrganoVIR is the first ITN to provide a novel pre-MBA programme and a Personal Developmental Plan to its researchers, allowing them to go beyond the lab and setting the new standard for future ITNs.
OrganoVIR has attained this goal by achieving its four research objectives: 1) Develop, standardize, and improve organoid models for virus research; 2) Understand human viral pathogenesis by using human organoids as infection models; 3) Apply organoids in antiviral compound testing; and 4) Assess ethical and societal impact of organoid technology and identify factors that drive investment in this new biotechnology.
To accomplish its goals, OrganoVIR has provided an innovative training programme aimed to deliver highly skilled researchers that are capable of implementing and sustaining organoid technology, as well as innovate virus research in the EU. OrganoVIR is the first ITN to provide a novel pre-MBA programme and a Personal Developmental Plan to its researchers, allowing them to go beyond the lab and setting the new standard for future ITNs.
OrganoVIR is divided into six Work Packages: 4 scientific Work Packages (WPs 2-5) that are guided by a newly designed training programme (WP1) and a management framework (WP6). The work performed and results obtained are provided per Work Package.
WP1 LEARN: An innovate training programme was designed comprising of various training courses in the areas of virology, organoids, IP, finance, entrepreneurship and communications. Furthermore, a tailored pre-MBA programme was designed. Upon completion of the programme, our researchers were awarded a pre-MBA certificate. All our researchers found the pre-MBA programme to be of great value for their current work and future career. Moreover, a tailored Personal Developmental Plan (PDP) was designed to help our researchers develop ‘soft skills’. Upon completion, our researchers were awarded a PDP certificate. The PDP has had a positive impact on the personal and professional lives of our researchers. Manuscripts about the pre-MBA programme as well as the PDP have been published on Open Research Europe.
WP2 DEVELOP: A co-culture model of human airway (HAE) and immune cells, a blood-brain barrier model and a human skin-like culture were developed. With the HAE co-culture, SARS-CoV2 could be studied and it was shown that macrophages are important in inhibiting this infection. Advancements were made with gelatin-based hydrogels to support co-cultures of gut epithelial and endothelial cells, and with specifically developed media for Apical Out Organoids, a new human airway organoid model for studying respiratory viruses. By establishing these different organoid models knowledge on 3D culturing expanded rapidly within the consortium.
WP3 UNDERSTAND: Successful infection of airway, gut and brain organoid models was established with a variety of viruses. This increased our insight in pathogenesis of virus infections in humans. The inhibitory effects of mucus on influenza viruses in airway epithelium was shown. Determinants for entry and transmission between epithelial cells of the airway exposed to coronaviruses were elucidated, and the capacity of coronaviruses to replicate in the human gut was shown. Airway cultures from patients with respiratory diseases were established to study virus-bacteria interactions in human disease. Several picornaviruses were studied for their preference for airway or gut for entry, and for their neuropathogenicity. This work showed the tremendous value of organoids for virus research.
WP4 APPLY: Organoids have been optimized to implement antiviral strategies against respiratory and gastrointestinal viral infections. To this end, human airway cultures and iPSC- or adult stem cell-derived intestinal organoid cultures have been successfully established to study infection with SARS-CoV2, noro-, rota- and parechovirus infections. Known or newly discovered antiviral compounds have been added to show that organoid-based antiviral testing is very well suited to support preclinical studies of antiviral drugs.
WP5 SHARE: A report has been provided containing a summary overview of the ethical issues regarding the derivation and use of organoids and an article has been published on how best to utilize a responsible research innovation framework for the development of complex and controversial organoid-entities. In the area of investing in new biotechnology, our research will advance the literature on signaling, categorization and entrepreneurial finance, add insights into the relationship between signals and investments in nascent ventures and provide valuable practical implications for a wide range of stakeholders, including entrepreneurs, investors, and policymakers.
WP6 NAVIGATE: OrganoVIR has hosted seven consortium events. To expand our communication and dissemination activities, OrganoVIR recruited a Science Communications Officer who has consistently disseminated information about the work performed as well as results obtained via the OrganoVIR website and its social media platforms. In addition, project publications have been published in scientific journals and disseminated via OrganoVIR’s communication channels.
WP1 LEARN: An innovate training programme was designed comprising of various training courses in the areas of virology, organoids, IP, finance, entrepreneurship and communications. Furthermore, a tailored pre-MBA programme was designed. Upon completion of the programme, our researchers were awarded a pre-MBA certificate. All our researchers found the pre-MBA programme to be of great value for their current work and future career. Moreover, a tailored Personal Developmental Plan (PDP) was designed to help our researchers develop ‘soft skills’. Upon completion, our researchers were awarded a PDP certificate. The PDP has had a positive impact on the personal and professional lives of our researchers. Manuscripts about the pre-MBA programme as well as the PDP have been published on Open Research Europe.
WP2 DEVELOP: A co-culture model of human airway (HAE) and immune cells, a blood-brain barrier model and a human skin-like culture were developed. With the HAE co-culture, SARS-CoV2 could be studied and it was shown that macrophages are important in inhibiting this infection. Advancements were made with gelatin-based hydrogels to support co-cultures of gut epithelial and endothelial cells, and with specifically developed media for Apical Out Organoids, a new human airway organoid model for studying respiratory viruses. By establishing these different organoid models knowledge on 3D culturing expanded rapidly within the consortium.
WP3 UNDERSTAND: Successful infection of airway, gut and brain organoid models was established with a variety of viruses. This increased our insight in pathogenesis of virus infections in humans. The inhibitory effects of mucus on influenza viruses in airway epithelium was shown. Determinants for entry and transmission between epithelial cells of the airway exposed to coronaviruses were elucidated, and the capacity of coronaviruses to replicate in the human gut was shown. Airway cultures from patients with respiratory diseases were established to study virus-bacteria interactions in human disease. Several picornaviruses were studied for their preference for airway or gut for entry, and for their neuropathogenicity. This work showed the tremendous value of organoids for virus research.
WP4 APPLY: Organoids have been optimized to implement antiviral strategies against respiratory and gastrointestinal viral infections. To this end, human airway cultures and iPSC- or adult stem cell-derived intestinal organoid cultures have been successfully established to study infection with SARS-CoV2, noro-, rota- and parechovirus infections. Known or newly discovered antiviral compounds have been added to show that organoid-based antiviral testing is very well suited to support preclinical studies of antiviral drugs.
WP5 SHARE: A report has been provided containing a summary overview of the ethical issues regarding the derivation and use of organoids and an article has been published on how best to utilize a responsible research innovation framework for the development of complex and controversial organoid-entities. In the area of investing in new biotechnology, our research will advance the literature on signaling, categorization and entrepreneurial finance, add insights into the relationship between signals and investments in nascent ventures and provide valuable practical implications for a wide range of stakeholders, including entrepreneurs, investors, and policymakers.
WP6 NAVIGATE: OrganoVIR has hosted seven consortium events. To expand our communication and dissemination activities, OrganoVIR recruited a Science Communications Officer who has consistently disseminated information about the work performed as well as results obtained via the OrganoVIR website and its social media platforms. In addition, project publications have been published in scientific journals and disseminated via OrganoVIR’s communication channels.
Immortalized cancerous cell lines and animal models remain the state of the art to study viral diseases to test antiviral drugs. However, there is a clear need for physiological human models to better understand how viral infections cause disease in humans. OrganoVIR aimed to bring progress beyond the state of art by establishing organoids as a superior model for virus studies and the testing of antiviral drugs. With successful development and implementation of organoids in virology, OrganoVIR has set a new horizon to study human virus infections, which is of high interest to both academia and industry.
Furthermore, OrganoVIR provides an unique European network that expands the application of organoids for virology in both academia and industry. By providing a multi-sectoral and innovative training programme, OrganoVIR provided interdisciplinary trained researchers that are internationally oriented, which will increase mobility. This is necessary to guarantee a leading position for the EU in innovative virology and to broaden the possibilities for EU companies to invest in organoid technology applications.
OrganoVIR has accomplished the following results:
• Successful adaptation of human organoids for virology
• The utilization of expertise on organoids and virology to standardize methods for assessing viral infections
• The development of a specialized media for lung organoids
• An increased understanding of how specific viruses (such as coronaviruses and picornaviruses) enter the human body and establish infection
• The characterization of antiviral molecules against specific viruses
• Standardization and extending of established organoid cultures for High-throughput screening
• Development of an ethical framework for the use of organoid technology
• Lead innovation in the fields of organoids for virus research
Furthermore, OrganoVIR provides an unique European network that expands the application of organoids for virology in both academia and industry. By providing a multi-sectoral and innovative training programme, OrganoVIR provided interdisciplinary trained researchers that are internationally oriented, which will increase mobility. This is necessary to guarantee a leading position for the EU in innovative virology and to broaden the possibilities for EU companies to invest in organoid technology applications.
OrganoVIR has accomplished the following results:
• Successful adaptation of human organoids for virology
• The utilization of expertise on organoids and virology to standardize methods for assessing viral infections
• The development of a specialized media for lung organoids
• An increased understanding of how specific viruses (such as coronaviruses and picornaviruses) enter the human body and establish infection
• The characterization of antiviral molecules against specific viruses
• Standardization and extending of established organoid cultures for High-throughput screening
• Development of an ethical framework for the use of organoid technology
• Lead innovation in the fields of organoids for virus research