April 18th 2024
Introducing Utrecht University – a CARE academic organisation
Introducing Utrecht University – a CARE academic organisation
Established in 1636, Utrecht University has a long history and is rich in tradition. Utrecht University was formed by the provincial government in 1636. Recognized as the leading Dutch university according to the Shanghai Ranking, it offers 45 undergraduate and 167 graduate programs, has some 30,000 students served by 7,500 academic staff. Today the university has seven faculties in Veterinary Medicine, Medicine, Science, Geosciences, Social and Behavioural Sciences, Humanities and Law, Economics and Governance.
The primary contributor to CARE from the university is the Virology section at the Faculty of Veterinary Medicine. The Virology section is studying various viruses (coronavirus, picornavirus, influenza, paramyxovirus) with the aim of developing innovative antiviral drugs, therapeutic antibodies and vaccine approaches.
The Virology section was started in 1971 by Prof. Marian Horzinek, who is considered a “Founding Father” of (veterinary) virology in The Netherlands. He started virology research at the university studying Feline Infectious Peritonitis (FIP), a deadly disease in cats due to infection with a feline coronavirus (FCoV). The section has longstanding and extensive experience in coronavirus research, specifically in
- Receptor identification and virus-receptor interactions
- Structure-function studies of the viral Spike protein, which is the protein involved in binding receptor(s) and mediating cellular entry and the main target for humoral immune responses, and as such a key viral protein for development of intervention strategies
- Determinants of coronavirus inter-species transmissibility
- Viral genome replication and virus-host interactions
- Development of intervention strategies (antibodies, vaccines, antiviral drugs) and diagnostics for (emerging) coronaviruses
The Virology section comprises approximately 45 members, including researchers at all seniority levels and support staff, rising to up to 60 researchers when housing students performing their MSc internships.
Why did Utrecht University choose to get involved in CARE?
The Virology Section has 50+ years of experience in coronavirus biology and possesses extensive expertise in both human and animal coronaviruses. They have particular expertise in virus structure, virus-receptor interactions, virus entry mechanisms, genome replication and virus-host interactions. The CARE project enabled them to quickly contribute their knowledge with many other research groups, while also benefitting from enhanced collaboration with the CARE partners.
What has Utrecht University delivered for CARE?
UU’s contributions span across various innovations and findings in Work Packages (WPs) 1, 2, 4 and 5. Overall, their efforts aim to identify potential antiviral drugs, peptides, nanobodies and antibodies, to understand their mechanisms of action, and to explore host factors involved in coronavirus infection, which could inform the development of effective therapies against SARS-CoV-2 and other related coronaviruses.
In WP1, they evaluated a large number of small molecules for antiviral activity against SARS-CoV-2 and other coronaviruses, characterized antiviral effects and performed Mechanism of Action studies to reveal their molecular mechanisms.
In WP2, they developed macrocyclic peptide inhibitors and nanobodies targeting the Spike protein of SARS-CoV-2. The team studied the site in Spike that is targeted by the macrocyclic peptide using cryo-Electron Microscopy (cryo-EM). This revealed that the peptide binds to a conserved region of the SARS-CoV-2 spike protein that has hitherto not been exploited by antibodies or small molecules and has not been mutated in any of the variants of concern.
In WP4, they established assays, reagents and structural biology workflows for the assessment and characterization of human neutralizing antibodies (nAbs) against SARS-CoV-2 and variants. The team generated bispecific antibodies to enhance potency and breadth of nAbs against SARS-CoV-2 and related coronaviruses. They also developed broad-spectrum nAbs against porcine deltacoronavirus (PDCoV), an emerging coronavirus with pandemic potential. Finally, they isolated and characterized human antibodies that target host receptor aminopeptidase N (APN). These antibodies are highly resistant to viral escape and can be employed for coronaviruses that share the same receptor for entry, increasing our pandemic preparedness against newly emerging coronaviruses.
In WP5, they determined changes in the metabolome in coronavirus-infected cells and identifying essential host factors for coronavirus infection via genetic CRISPR-cas9 screens. In follow-up experiments, they are investigating the physiological importance of the virus-induced changes in metabolism and the role of the identified host factors for efficient virus replication and/or evasion of infection-limiting host antiviral responses.
For more information about the different work packages, please click here
Who is working in the CARE team at Utrecht University?
The Utrecht University team is led by two Principal Investigators: Professor Dr Frank van Kuppeveld who studies the interaction between viruses and their host; and Dr Berend Jan Bosch (Associate Professor) who studies virus-receptor interactions and cell entry mechanism of membrane-enveloped viruses, particularly coronaviruses.
During the CARE project, Dr Daniel Hurdiss, a structural virologist, was promoted from a post-doctoral researcher to Assistant Professor. He is a structural virologist who, among others, uses cryo-EM to study the 3D structure of viral proteins and understand their functional implications.
Many of UU’s virologists have been involved in CARE from the beginning, all aiming to translate their knowledge into intervention strategies targeting either viral entry and/or replication: Frank Buitenwerf, Marianthi Chatziandreou, Oliver Debski Antoniak, Tim Donselaar, Wenjuan Du, Preeti Hooda, Ruben Hulswit, Yifei Lang, Joline van der Lee, Rutger Luteijn, Wendy Meijer, Vera Nijman, Lonneke Nouwen, Collins Owino, Judith Oymans, Itziar Serna Martin, Jill Ver Eecke, Marleen Zwaagstra. In the first year of CARE, the group of Alexandre Bonvin (Computational Structural Biology) at the university’s Faculty of Science also contributed to CARE.
What benefits have Utrecht University experienced through being part of CARE?
The Utrecht University Virology team has enjoyed the following benefits:
- Access to a broader range of expertise, technologies, and facilities.
- Opportunities to work alongside industry partners, other academic institutions, and governmental agencies which fosters knowledge exchange, interdisciplinary research, and the pooling of diverse perspectives and skills.
- Academic researchers’ opportunities for networking, professional development, and establishing collaborations with leading experts and institutions in the field.
- Support to conduct cutting-edge research, accelerate progress towards the development of effective therapies, and make meaningful contributions to the global effort to combat infectious diseases.
Want to know more about Utrecht University?