University of Minho PhD students Graça Pinto and Rodrigo Monteiro asked Dr. Evelien Adriaenssens, group leader at the Quadram Institute, about her career studying phages and viromes, her thoughts on manipulating microbiomes with viruses, and how viral classification is changing.
Can you start by telling us a little about your background and current research interests?
Evelien: I studied at the University of Leuven, in Belgium, and I have a degree in Agriculture Engineering from the Faculty of Bioscience Engineering. During my master’s, I was working on something not bacteriophage-related, but, since I was partially in the lab of Professor Rob Lavigne, I saw all the interesting work that everyone was doing with phages.
I did my PhD on the use of bacteriophages to combat the emergent bacteria Dickeya solani on potato plants. We had interesting results, and we sold the phages to a company that continued to work on them. After my PhD I wanted to learn more about bioinformatics, so I went to South Africa to join a lab that was doing microbial ecology, called the Centre for Microbial Ecology and Genomics. They were starting a project on metaviromics (viral metagenomics) of deserts. In the 3.5 years of work on this project, I learned about global viral diversity and how to use bioinformatics tools.
Later, I was recruited by the University of Liverpool, because of the bioinformatics and viromics skills that I developed. They were starting a project on the use of viromics to find pathogenic viruses in the environment when it comes to wastewater contamination of the river system and whether viruses end up in the food chain. That was perfect for me; I could expand my knowledge of viromics since I was specifically looking for norovirus, a virus that makes you vomit and gives you diarrhea.
While in this project, I got interested in viruses that are associated with the human gut. I wanted to use what I learned about phages and viral diversity to see what was going on with the human gut, so I started a research group at the Quadram Institute in the Department Gut Microbes and Health in Norwich, UK, in January 2019. Our institute is focused on investigating human gut microbiome health, how that intercalates with the food we eat, and microbes from the food chain that can potentially make us sick. My focus is on the gut virome and how we can use phages in the virome to increase health or reduce disease.
You went from biotechnological use of phages to a wider knowledge of the virome. How was the transition?
Evelien: It was challenging in a way, but it was what I wanted for my first post-doc. I wanted to use my knowledge of bacteriophages on a larger scale, so, instead of looking at one genome, I was looking at thousands of genomes, while improving my bioinformatic skills. This is a process that is not finished, as I am still learning new bioinformatic skills every day. I never called myself a bioinformatician, but I do use a lot of bioinformatics tools. Now I am trying to integrate everything into my research group. I think I did some nice jumps so that, when I combine everything now, I can create a good research environment where there are a lot of different angles that we can use.
In the different habitats that you studied—the deserts, the rivers and now the gut—how important do you think virome is?
Evelien: I think, in a lot of environments, viruses were understudied just because there were no tools to look for them. Most of the early microbiome studies were done using 16S sequencing, but there is no such universal gene for viruses, so people conveniently ignored them. Especially bacteriophages; in every environment where bacteria are important, the bacteriophages are also important. Bacteriophages make sure that you have population turnover, and there are a lot of temperate phages that integrate into the genomes, providing other genes that are important for bacteria to become more virulent. The crAssphage story in the human gut is very important, and one of the things I assisted with in my previous project was see whether we could use crAssphage as a marker for wastewater contamination of the environment. We were relatively successful, but it turns out that all of the environment was contaminated. So, I think viruses, and particularly phages, are important in every environment.
As you said, only now are phages and the virome in general being looked at in these kinds of studies, because we have new tools that allow us to do that. But do you think that the boom in the studies relating to microbiomes has also contributed to the boom in virome studies?
Evelien: Yes, I think that when it comes to microbiome and virome studies, the virome is lagging on the microbiome. So, whenever the microbiome is important the virome will also be important. We need to make sure that we don’t make the same mistakes as the microbiome field in general did, regarding over-hyping things. It is important but it is not the solution to world peace. What I hope to find and to do, as there are specific bacteriophages that can work on specific bacteria, is for example, to use bacteriophages to knock out one member of the microbiome, without causing a cascading effect, rather than altering the entire microbiome at the same time. This is one of the things that we are investigating now: what are the cascading effects in the gut microbiome, if we use a phage or if we try to knock something out? It is very important to define/to find the culprit of the disease. In many diseases, there is no simple solution, because what causes it is a combination of factors, and to think that one bacterium, one bacterial strain or one phage will give you the answer is a bit naïve. Nevertheless, in other cases, it is very well described, as with the important work that Martha Clokie does with Clostridium difficile: that is a very clear case where a particular bacterium causes a very clear disease. I think that there are a lot more of those diseases, but we need to take care in finding those, so we can focus on those and not on everything at the same time.
In parallel to your research, you are the Chair of the Bacterial and Archaeal Viruses Subcommittee of the ICTV and the chair of the Caudovirales Study Group. What exactly does this imply?
Evelien: Since February, I have taken over from Andrew Kropinski as the chair for the Bacterial and Archaeal Viruses Subcommittee. When I was the vice-chair, I was Andrew’s right-hand person, now I am in charge, meaning that I am now also part of the Executive Committee of the ICTV. I was chair of the Caudovirales Study Group because it gave me a good oversight of everything that happens with tailed phages, but now I oversee all phages. The ICTV has been given the power, decades ago, by the International Union of Microbiological Societies, to be in charge of viral taxonomy, meaning that we create new species, genera, families and so on. When a new phage gets isolated, we can see the closest relatives, if they fit in the same species or the same genus, and we define the thresholds and the criteria for classification. Finally, we communicate that, for example, to people at NCBI, who then adapt and use it to classify and structure their reference database.
Recently, the committee changed one family, Myoviridae, creating two more families. What was the purpose of that?
Evelien: We are moving from a morphology-based taxonomy to a genome-based taxonomy. Unfortunately, we don’t have the time or resources to do it all at once, because we do this as volunteers. So, Myoviridae, Podoviridae, and Siphoviridae are the families of tailed phages according to the tail structure. Now, as more phages have gotten sequenced, we’ve seen that there are more differences within a family than what you can contain at the morphological level, especially if you compare to eukaryotic viruses. Furthermore, some phages of two different families are more related to each other than with other members within the family. This creates confusion, particularly when you do metagenomics and you only have the genome information; you can easily reach the wrong conclusions. So, we started to break up these families into new ones that are based on all sorts of genomic, phylogenetic, phylogenomic, and core gene analyses. There is a large range of bioinformatics methods that come with defining a new family. We first did the Ackermannviridae and then we published a paper on the new family, Herelleviridae, where we described all the steps that were taken. The goal is to do it for all tailed phages in the next couple of years, so there will be no more Myoviridae, Podoviridae, Siphoviridae, but only the new families that have the genomic context. This means that the term ‘myovirus’ will just be the description of the morphology.
At the Viruses of Microbes conference, you and Dr Andrew Kropinski are going to give a workshop. Can you give us a sneak peek?
Evelien: There will be two big sections. One will be about phage genome annotation, what you do if you have a new phage sequenced. Some of the tips and tricks that Andrew Kropinski knows very well about best practices when defining the ORFs, what is a gene, looking for Shine-Dalgarno sequences. All to lead to a nice finished genome sequence that you can submit to a public database. In the second section, we will go through some of the tools that we use to classify phages and give some tips and tricks for your phage classification. This way, you can go from a Genbank sequence submission to an official classification.
What are your expectations for the rest of the conference?
Evelien: I have been going to the Viruses of Microbes conferences since it started in Paris in 2010. They are always very interesting, and as somebody who kind of does a little of everything, one of the many things that I like about Viruses of Microbes is that it also talks about research other than phages. Things that I don’t know much about, but I am very interested in—you don’t always have time to be on top of the literature with that. That is what I love about Viruses of Microbes, but also at the same time seeing all my colleagues again and interacting with them, and hopefully starting some new collaborations.
This issue was produced in collaboration with the Viruses of Microbes 2020 Organizing Committee. The conference, originally planned for July 2020, will be postponed to July 2021.
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