CARE’s Young Researchers – Introducing Holly Kerr, PhD, University of Edinburgh

Read about how Holly’s work in getting a better understanding of host response and resulting disease may help identify alternative or complementary approaches to direct-acting anti-virals by targeting the host.

CARE (Corona Accelerated R&D in Europe) is the largest European research initiative addressing the challenges of COVID-19. It comprises 38 partners, from both industry and academia, in a set-up of eight multidisciplinary work-packages (WPs). In this series, we highlight the work of some of the young researchers involved in CARE as part of their PhD or postdoctoral work. Here, we learn how this opportunity has benefited Holly, while simultaneously benefiting CARE and its ambition to help society defeat COVID-19 and future pandemics.

What experience did you have working on a Public Private Partnership before joining CARE? 

I had no experience of being in a consortium of this type within a research context. However, before starting my PhD in 2020, I was recruited as a Laboratory Scientist at one of the UK’s Lighthouse Laboratories that were responsible for the mass COVID-19 testing effort. These labs were only possible due to a huge collaboration between industry, academia, and government. Working at the Lighthouse Lab gave me my first insight into the importance, impact and challenges of this kind of partnership.

Why did you decide to get involved in CARE?

My PhD project within the Tait-Burkard lab aims to better understand the host factors involved in SARS-CoV-2 and other human coronavirus infections. This includes following up the results of an RNAi Druggable Genome screen which was conducted as part of the CARE work package 5 research. Starting my PhD during the pandemic and following the work in the Lighthouse Lab, I was motivated to align my research project with the pandemic response. I was inspired by the cross-disciplinary and well-supported team effort that IMI CARE champions and feel grateful to have this consortium as a network within my research.

How did your involvement in CARE come about?

I was encouraged in the planning of my PhD project by my supervisor, Christine Tait-Burkard, to be involved in CARE, given my interest in host factors, antivirals and pandemic preparedness.

Tell us about the work you have been doing in the CARE consortium

My role in the CARE consortium involves analysing and validating an in vitro RNAi host factor screen of SARS-CoV-2 as part of the aims of Work Package 5. I have generated hit lists of genes involved in SARS-CoV-2 infection from the screen, compared these to host factors identified in other published work, including results within our work package, and conducted pathway and network analysis of our hits. I’ve validated two clusters of hits from anti-viral and pro-viral pathways and begun to decipher their role in infection. Identified host factors in our screen are “druggable”, in that drugs exist that target them, or are they are predicted to be targeted with drugs based on their structure. To follow up the results of our screen, I have been testing the use of repurposed host-directed anti-viral therapies in SARS-CoV-2 infection in vitro and I am planning to take forward promising candidates to an in vivo study this summer.

What highlights can you share from your time in the CARE consortium so far?

The highlight from my time in CARE has been attending the annual meeting in March this year in Leiden. It was exciting to see my work presented and helpful to receive feedback from a global group of experts. I really enjoyed meeting researchers from across the consortium, learning about the development of multiple promising treatment options from across the other work packages and being a part of the strategic discussions for the future of the consortium as we prepare for the next pandemic. As an early career researcher, these conversations are not often made accessible to me – I appreciated the opportunity to have the insight into decision making processes at this level.

Why does this work matter?

This work matters because despite the vast amount of research conducted following the emergence of the third highly pathogenic human coronavirus in the past 20 years, we are arguably still some way from being prepared for the next pandemic. In particular, we are yet to find effective, broad-spectrum, “off-the-shelf” therapeutic options. Coronaviruses continue to burden human, animal and environmental health and there is a risk of further emerging strains. By understanding the host response, we can better understand the resulting disease and perhaps identify alternative or complementary approaches to direct-acting antivirals by targeting the host.

What are or were the biggest challenges you have experienced (and how did you overcome them?)

Challenges I have experienced include keeping up with the variants of concern that evolved in real-time during our research. This was overcome though collaboration with clinical scientists and teamwork within the Tait-Burkard lab.  We divided the labour to harness different skills from different scientists doing different tasks, including growing virus, testing stocks, sequencing, and then running relevant assays that tell us more about how the latest variants interact with the host within human cells.

How have you benefited from your involvement in CARE?

I have benefited by gaining insight into leading research in coronavirus biology, meeting experts from across Europe and putting my research in the context of other work under the same aim.

What advice would you give to someone getting involved in a Public Private Partnership? 

I would tell them to do it, grab the opportunities that arise and try to enjoy the feeling of being the least experienced person in the room – it means you have the most to learn!

CARE’s Young Researchers – Introducing Thijs Steijaert, PhD student, Leiden University Medical Centre

Meet Thijs! Thijs Steijaert is a PhD student at Leiden University Medical Centre and in this short video, describes for us his role in CARE Work Package 5, where his work is contributing to growing scientific knowledge of our understanding of host pathways involved in replication and pathogenesis of the SARS-CoV-2 virus using proteomics and phosphoproteomics. Take a look at this 50 second video to find out why this work, and the opportunity to take part in the CARE consortium, matters to Thijs.

CARE – Infographic: Work Package 2 Target-based drug discovery and design.

CARE has 8 Work Packages but do you know what each one does? Here, you can learn about the Work Package 2 team, their objectives, their partners, their breakthrough moments and more.

The infographic is also available here

Published in Viruses: Lower infectivity of recent SARS-CoV-2 omicron sub–variants in Syrian Hamster.

The CARE partner, KU Leuven (KUL) evaluated the infectivity of two important sub-variants of omicron in Syrian hamsters. Indeed, since the emergence of the first omicron SARS-CoV-2 variant at the end of 2021, several sub-variants have evolved and become predominant in the human population, showing enhanced transmissibility and ability to (partly) escape the adaptive immune response. These include EG.5.1, an XBB sub-variant, and BA.2.86, a phylogenetically distinct variant, which were compared to the BA.5 sub-variant, a preceding BA.2 descendant. The BA.2 variant was not chosen as a comparator as it does not replicate efficiently in the KUL hamster model as compared to the BA.5 sub-variant.

Both EG.5.1 and BA.2.86 sub-variants are attenuated in Syrian hamsters as compared to the BA.5 sub-variant, as shown by lower infectious titers in the lung and lower lung pathology scores, while the viral RNA loads in throat swabs were comparable in the 3 strains. Interestingly, no virus titers in the lungs of the hamsters infected with the BA.2.86 sub-variant were observed although high viral RNA loads were detected. Therefore, viral RNA loads in the throat swabs and the lungs as well as lung histopathology scores could be a more suitable readout for vaccine and antiviral studies involving these two new sub-variants.

The continuous emergence of sub-variants will remain a challenge as it may require updating vaccines and therapeutic antibodies. Pre-clinical models with the evolving sub-variants are therefore crucial not only to study the virological characteristics of these new sub-variants, but more importantly to evaluate the efficacy of updated and also novel vaccines as well as therapeutic options for which the efficacy is virus variant dependent such as neutralizing antibodies.

To learn more, click here: Comparing the Infectivity of Recent SARS-CoV-2 Omicron Sub-Variants in Syrian Hamsters

CARE’s Young Researchers – Introducing Wenjuan Du, Post-doctoral researcher, Utrecht University

Read about how Collins’s work in understanding how the coronavirus hijacks human host factors and processes has provided us with opportunities to develop therapies to inhibit viral replication.

CARE (Corona Accelerated R&D in Europe) is the largest European research initiative addressing the challenges of COVID-19. It comprises 38 partners, from both industry and academia, in a set-up of eight multidisciplinary work-packages (WPs). In this series, we highlight the work of some of the young researchers involved in CARE as part of their PhD or postdoctoral work. Here, we learn how this opportunity has benefited Wenjuan (Utrech University), while simultaneously benefiting CARE and its ambition to help society defeat COVID-19 and future pandemics.

What experience did you have working on a Public Private Partnership before joining CARE? 

Before joining CARE, I had limited experience working in Public Private Partnerships.

Why did you decide to get involved in CARE?

I completed my doctoral studies in June 2020, at a time SARS-CoV-2 had become a serious health problem worldwide. I was highly motivated to contribute to the fight against SARS-CoV-2 and saw CARE as an excellent network to join.

How did your involvement in CARE come about?

My involvement with CARE stemmed from my doctoral research within the Virology laboratory at Utrecht University. My experience with molecular virology, antibody expression and neutralization assays made me well suited for the antibody research endeavors within Work Package 4 of the CARE research program.

Tell us about the work you have been doing in the CARE consortium

Within the consortium, my responsibilities have been diverse. They included setting up assays monitoring SARS-CoV-2 variants and characterizing antibodies that were developed by our WP4 partners. We evaluated the neutralization potency and breath of SARS-CoV-2 antibodies by using a pseudovirus system. More recently we started to develop human monoclonal antibodies against the emerging porcine deltacoronavirus (PDCoV), to enhance pandemic preparedness against this virus which can infect humans. We identified several antibodies with virus neutralizing activity, one of which targets a conserved epitope that is shielded from antibody recognition by other domains in the natural spike conformation. This antibody exhibits broad reactivity against related deltacoronaviruses and shows potential for future therapeutic use. Our studies on these antibodies have also provided more insight in PDCoV Spike-mediated cell entry. These findings are soon to be published in Nature Communications.

What highlights can you share from your time in the CARE consortium so far?

Highlights from my time in the CARE consortium include identifying antibodies with broad neutralization activity, particularly those that target conserved epitopes. These results have given me a great sense of accomplishment.

Why does this work matter?

Our research has deepened our understanding of the humoral immune response to combat  coronaviruses and the potential for these RNA viruses to evade from it. Our efforts have underscored the potential of antibodies targeting conserved epitopes on the spike protein to serve as therapeutic agents against future emerging coronaviruses.

What are or were the biggest challenges you have experienced (and how did you overcome them?)

I have benefited by acquiring new experimental skills, strengthening critical thinking, and expanding my professional network. Additionally, CARE provided me the opportunity to work with a great team of scientists in Utrecht, as well as with other scientists from academic and private partners within WP4, which was a rewarding and enriching experience.

How have you benefited from your involvement in CARE?

I have benefited immensely by interacting with experienced industry and academia experts who are willing to mentor and guide the upcoming scientists within the consortium. I have been able to sharpen my technical as well as interpersonal skills since I joined the consortium.