Breakthrough research at Masaryk University

Since 2018, the scientists at Masaryk University in Brno have been researching how viruses release their genomes. Recently, their third article was published in the prestigious magazine ACS Nano by American Chemical Society (ranking 243 out of 5554 peer-reviewed journals) and caught attention of the media.

What’s their research about? We’ve asked one of the scientists working on the project. Lukas S. was already interviewed by us about his PhD studies in Brno a few months ago. After the article in ACS came out, he was kind enough to tell us about the fascinating project in more detail.

Sorry for such a blatant question but you’re primarily a physicist so how come you study viruses?

It’s actually a very good question because not many people know that what happens to a virus in human cells is, in fact, mostly a physical phenomenon. One would maybe expect that what happens in bodies of living organisms are chemical reactions, in other words changes to chemical structure of matter. For example, when carbon and oxygen turn into carbon dioxide during the process of burning.

However, such processes are in the minority, a lot needs to happen before an actual chemical process takes place. Organic molecules do interact with each other but mostly it’s too weak for a chemical reaction to happen. Imagine it rather as a game of billiards—small and big molecules are constantly bumping into each other, and sometimes when the right molecules hit each other, they can stick.

Then when you have several big molecules stuck together, they can facilitate a chemical reaction. That’s how synthesis of all the tissues of our bodies work. First two parts of a ribosome come together, then an RNA chain gets stuck in them in the right place, then over a period of time a messenger-RNAs molecules hit this amalgamation and add bricks (residue) to a newly built molecule, a protein.

Only the creation of a connection between the brick and the protein is a chemical reaction, all that preceded it was a physical process. All that happens several trillion times every second naturally in our bodies. On the micro scale, that’s how organic matter behaves. It’s never tranquil, always moving.

Why is your research so useful?

If we discover how the process of virus releasing its genome works, we can then create certain substances that will induce such a process or prevent it, effectively creating a new anti-virotics. You’d want to induce it outside cells where it’s not harmful and prevent its release inside cells.

Right now, typical viruses work like this—they get into cells they’re programmed to invade because they carry certain proteins which acts as „keys“ that grant them access to cells carrying „locks“. Once inside, the virus disintegrates and its genome starts to multiply, the cell’s own ribosomes start building the proteins from viral genome, copying the virus. This will eventually kill the infected cell, infect the surrounding cells and make the host sick. What we want to do is to use those viruses to be beneficial for us. They could be reprogrammed to deliver medicine into certain cells instead.

I’ll give you a concrete example. Contemporary chemotherapy works on the principle that cancerous cells eat more than healthy ones. Chemotherapy is basically a weak poison that, if present in sufficient concentration, kills the cell. Cancerous cells, being such gluttons, eat most of the drug you deliver to the body so they are basically poisoned. While this can get rid of cancer, the person undergoing the treatment gets anaemia and loses their hair which is an unpleasant side effect because healthy cells are also affected.

What we’re trying to achieve is make viruses deliver those drugs only into cancerous cells and leave the healthy ones be. Viruses are ideal for it because that’s their function. Some vaccines against Covid-19 actually already work with this discovery. It’s called viral vector vaccine with examples like Johnson/Janssen, Astra-Zeneca and Sputnik.

That’s fascinating. Your particular research is about catching the virus in the moment when it opens to release its genome which is such a short time that one can’t even imagine it. How come you were the first ones to work on that? Has someone attempted it before?

We’re indeed the first in the world who managed it. It’s highly improbable to capture the precise moment because, as you pointed out, it’s so unbelievably quick. I guess we were lucky and it was a combination of factors. We got the results of such disintegration from prof. Plevka’s Cryo-EM experiments. They study the simplest viruses and the research data in this area expanded greatly over the last ten years. We needed the latest discoveries and technologies to model it.

How is your research going to continue?

There’re several ways actually. To release its genome, the virus has to get virus activated which happens in a cell organelle called endosome. Later, the endosome disintegrates, the virus enters into the cell proper where it disintegrates as well and its genome takes over the cell machinery. So far, we were researching only the virus disintegration part.

Another possibility is that the endosome doesn’t disintegrate but the virus does so its genome has to get out somehow. So far, we’re not sure how that happens. We can also evaluate the role of the endosome during the disintegration of the virus. There’re still many things we can pursue.

What would you recommend to students who are finishing their master’s and are considering applying for PhD in sciences? Is it for everyone? Do you maybe have some tips on how to choose a good university and find your supervisor? How many people who finish their PhD actually continue pursuing serious research?

I would start with emphasizing that science never stands on an individual ability. In sci-fi movies, it’s always the hard-to-understand scientist who solves problems within moments or a single genius who is so far ahead of others that no one understands what they’re doing. However, in reality, the work is tedious and you will spend months with no progress at all.

Additionally, you alone will have limited impact on what and how you do the research. Rather, it’s more in the line of: a) the right place (scientific group using some methodology focusing on some research area), b) right time (your work will always be built on what others have done before) and c) a person, you, with sufficient ability to perform the work.

Then there is the cold hard truth of statistics. Only about a half of the people who enrol finish their PhD and that is the easy part. Only about 10% of PhDs manage to find a long-term position in academia. In the meantime, they travel across the world. Staying a year or two here and there. Usually not even being employees, but on a scholarship—being without health-insurance for half a year every year with a wage comparable to most cashiers.

Here are some tips for those who think they will beat the odds.

The right place: Firstly, never accept a position as a PhD candidate on the scholarship alone. In the Czech Republic, the scholarship is now 12 000 CZK. You can’t survive on that. Also, if your supervisor won’t offer you additional pay from a grant, it means he doesn’t have one. Not having a grant means they are not producing good science. Stay clear of those supervisors. Try to find a salaried position at a university of renown with a supervisor who regularly publishes in Q1 journals.

The right time: Seemingly you can’t choose when you will do you PhD. But you can choose fields which are growing, with great promise for the future or of easy publications due to the hype (I’m looking at you, covid-19 articles). Unfortunately, you would need a PhD in the field to know if the particular field of study is dying or not. So again, be lucky.

The right skills. For most people, science is data, facts, evidence. All content, no form. Well, true science happens when you interpret the data—when you convince people of your simple idea born out of the data. Consider Darwin. Did he simply write a short report detailing the unique shaped beaks of birds on Galapagos islands? No, he formed a hypothesis, supported his arguments for it with data and convinced others.

Thus, knowing some epistemology to understand how to build valid arguments. Being a good public speaker and knowing how to write engaging and convincing texts is immensely useful because as a scientist you will be judged not by the work you do (since only you will understand it), but how well you present your work and convince others of its importance.

Picture note: Viruses don’t have colours because they’re smaller than the visible light’s wavelength. The colours in the model are only for your better illustration.

Additional resources:

Read the research paper

Animated model of the genome release