Dr G. Dudas Receives an EMBO Grant to Set Up a Lab: Aims to Assess the Ability of Viruses to Enter Vertebrate Cells

Dr Gytis Dudas, a virus researcher at Vilnius University Life Sciences Centre (VU LSC), is one of two young scientists at VU LSC and one of 11 European scientists who received a grant from the European Molecular Biology Organisation (EMBO) to set up their own laboratory this year. According to Dr G. Dudas, perseverance was the key to achieving his goal. He will set up his laboratory to carry out studies assessing the ability of surface proteins from several orthomyxoviridae, distant relatives of the influenza virus, to penetrate vertebrate cells.

Congratulations on receiving an EMBO laboratory installation grant. How did you feel when you heard about it? What was the most challenging part of achieving it? And most unexpected?

Thanks! Though I felt great, the feeling also wore off rather quickly when I remember that hundreds of other tasks await me. Most of all, I’d say this success made me reflect on a whole string of failures to get other forms of funding even when I got quite far (i.e., to the interview stage for the Henry Wellcome postdoctoral fellowship). I’d say what helped me get the installation grant the most, was determination and a couple of years of independent research away from my former supervisors and colleagues, whether I liked it or not.
These experiences included organizing Lithuania’s SARS-CoV-2 genomic surveillance and other projects I took on after leaving Trevor Bedford’s laboratory in Seattle. What surprised me the most was the contrast between how I felt I did during the interview with the EMBO panel and the obviously positive decision by the committee to award the installation grant to me, but perhaps that’s just me being overly self-critical, or maybe other candidates had worse luck that day.

The EMBO Installation Grant is for a specific project called "Characterising metagenomically discovered orthomyxovirus surface proteins". What is this project?

The EMBO-funded project aims to assess the ability of surface proteins of several Orthomyxoviridae, distant relatives of the influenza virus, to enter vertebrate cells. The risk of a particular RNA virus-causing disease is usually assessed retrospectively, i.e., a virus is considered to be likely to cause disease after at least one case of disease associated with that infection has been reported.
At the same time, the ever-increasing affordability of sequencing over the last ten years has uncovered a vast diversity of RNA viruses in arthropods (insects, arachnids and their relatives), but the use of this information so far has been superficial, with a greater focus on the distribution of different viruses across hosts, locations or populations, and less attention paid to the evolution of the viruses discovered, their dynamics over time, and the integration and joint analysis of the genetic sequences discovered by earlier and different studies.

How does the virus work?

My previous research, incorporating sequencing data from several different studies, has shown that one virus discovered during such searches for new viruses, the unimaginatively named Wuhan mosquito virus 6, is likely to infect vertebrates (we suspect birds). It is also likely that this trait is not unique to this virus but is also found in other related orthomyxoviruses due to the presence of the surface protein gp64 in this group. One of the functions of viral surface proteins is to bind specifically, like a key and lock, to molecules on the surface of the host cell (called receptors), which is the starting point for the entry of the viral particle into the host cell and the initiation of infection.
We have reason to suspect that the surface protein gp64 of orthomyxoviruses found in insects (such as Wuhan mosquito virus 6) uses host receptor proteins that are very important for the cell (and therefore conserved during evolution), and that differ little between insects and vertebrates, i.e., the gp64 'key' is capable of unlocking the 'locks' of many cells, since the latter are not very diverse.

How do you find that out?

This project will test the ability of different orthomyxovirus gp64 surface proteins to enter avian cells using pseudoviruses, to assess the potential of viruses carrying these proteins to cause zoonotic infections in vertebrates. Pseudoviruses are a safe experimental platform based on viral particles that are unable to replicate themselves (i.e., they are able to enter the cell but not escape) and that carry on their surface, but do not encode in their genome, the desired viral surface protein.
This system is commonly used to study proteins belonging to viruses that may be too dangerous, i.e., in the case of Ebola virus, any experiments must be carried out in biosafety level 4 laboratories (BSL-4). The pseudovirus system can be used to study just the surface protein of Ebola virus called GP safely in biosafety level 2 laboratories (BSL-2), which also have high but more attainable safety standards.

Is Wuhan mosquito virus 6 found in Lithuania?

Wuhan mosquito virus 6, currently found on all inhabited continents, is likely circulating in Lithuanian mosquitoes too. At the end of the project, I hope to better understand the threat to public health and/or livelihoods posed by this virus and its relatives and to assess whether such a threat exists at all. Most of all, I hope that the results of the project will become a springboard for further funding and development of research into this interesting family of viruses in Lithuania.

What kind of research team will be needed to implement your project? Whom will you collaborate with?

Though I will not be looking for new team members this year, I would recommend anyone who has a PhD, molecular biology skills and experience with pseudoviruses in the lab and who would like to contribute to this unique direction of virus evolution research to reach out to me since I hope to hire a two-year postdoc for this specific project in 2024. Of course, I’m also always on the lookout for talented young researchers who are interested in viruses and evolution to do a PhD in my lab.

What advice would you give to other researchers who may be considering applying for an EMBO grant?

I would advise my colleagues to be determined and ambitious. It is an open secret that scientists working in Lithuania are lagging behind in procuring international funding despite our membership in the European Union and initiatives to reduce this gap. Whoever doesn’t try to get international funding ends up not getting it, and the disappointment that you feel when you don’t get the funding is not the end of the world, so I would encourage my young colleagues to never give up and to aim higher.

The EMBO Installation Grant is €50,000 per year for three to five years. Of this, €35,000 is paid annually by the EMBO member countries (in the case of Lithuania, by the Research Council of Lithuania) and the rest by the EMBC (European Molecular Biology Conference), which funds EMBO. Grant winners can apply for additional small grants (up to €10,000 per year).
Scientists who have received an EMBO grant become members of the EMBO Young Investigators Network, and are provided with professional support and access to state-of-the-art research facilities. In addition, they have access to other financial and information support from EMBO to help them develop contacts and skills.
Dr Patrick Pausch, a researcher at the VU LSC EMBL Partnership Institute, has been awarded a grant, together with Dr Dudas, to set up the EMBO Lab in 2023. In 2021, Dr Algirdas Toleikis, a young scientist at the VU LSC, was awarded an EMBO Installation Grant.