Over the past few years, Dr. Ieva Plikusienė, a researcher at the Center for Physical Sciences and Technology (FTMC), has become a true rock star in Lithuania and abroad.
A senior researcher in the Department of Nanotechnology, she has been recognised for her work on the interaction between SARS-CoV-2 proteins and antibodies. In 2021, she was the winner of the L'ORÉAL-UNESCO For Women in Science International Awards, and in 2022, she was recognised as one of the most promising young scientists worldwide, winning the prestigious UNESCO International Rising Talent Award.
In December, the icing on the cake was that Dr. Ieva Plikusienė was named the Woman of the Year 2022 by the Lithuanian website Lrytas.lt magazine "Stilius".
She has given numerous interviews - from comments on the importance of the awards to stories about her love for her husband and daughter. Now, let's take a closer look at the research she has been doing, what it means for all of us - and what it all looks like.
(Dr. Ieva Plikusienė. Screenshot from video of L'Oréal Group's Facebook account)
Anxiety turned into successful work
The early 2020s. News of the coronavirus rage in China is becoming more and more prominent in daily news - until finally the subject takes all the attention completely. The virus spreads to Europe, killing thousands in Italy, and at the end of February we hear of the first case in Lithuania.
"When we heard about the coronavirus, we were very worried, we didn't know what would happen. As scientists, we realised that very little was known about the virus, and we didn't know how it would mutate," recalls Dr. Ieva Plikusienė. But after the initial shock wore off, she and her colleagues had an idea: after all, we have a lot of experience on researching interactions between antibodies and antigens. Why can't we use that in this situation?
Then a joint team of scientists from FTMC and Vilnius University successfully produced the first publication, which was published in the high-profile Journal of Colloid and Interface Science in early 2021. "We carried out the experiments, wrote the paper and published it in a few months - which is very fast," she says.
In the lab, COVID-19 was not dangerous to study because the work was not on the viruses themselves, but on their proteins. Initially, it was not yet possible to buy them anywhere, but the Vilnius University Life Sciences Center (with Dr. Aurelija Žvirblienė at the forefront) and biotechnology company Baltymas helped to solve this issue. Company produced the coronavirus "spike" proteins, and A. Žvirblienė's team produced the antibodies. The published article is also unique in that all the research (as well as the production of the proteins) was carried out in Lithuania.
This work will be the first of its kind to receive international recognition. Antigen VS antibody interaction studies are a very promising field, and knowledge of this field can lead to the development of ever better biosensors.
How to make sense of it all? We'll explain in a moment.
The golden age
A biological sensor (or just biosensor) is a tiny device that uses biologically active substances. One of the simplest and most common examples is the COVID-19 rapid test for disease detection.
Dr. I. Plikusienė explains that a pregnancy test is exactly the same biosensor. It contains certain biologically active substances that recognise and bind to each other. Then, usually gold nanoparticles are attached to them, which is why we see the two red stripes: the pregnancy test is positive and you are crying with happiness (or shock, depending on the situation).
"The field of biosensors is a scientific topic that is now in its golden age," says the FTMC scientist. "The development of such devices is very important because they help to diagnose diseases or conditions in time, before they start - for example, by detecting tumour markers and thus possibly preventing cancer.
But before such simple and quite cheap sensors can be developed, there is a lot of work to be done on the molecules themselves - which molecules to put in a rapid test? What antibodies are needed to detect the antigen well? So that it recognises what it needs to, not just anything?"
(Image from Wikipedia.org)
The battlefield called My Body
Ieva Plikusienė has found a new, reliable way to answer these questions. Before we do that, let's remember what antibodies and antigens are - and how important their interaction is.
Antibodies are Y-shaped protein molecules that are responsible for our body's defence against foreign organisms (such as viruses or bacteria). Antibodies are produced by our immune system when it senses a threat.
Antigens are molecules on the surface of those viruses or bacteria. It is the antigens that are the primary "target" of antibodies: they recognise the foreign body, bind to the antigens and thus neutralise the rogue virus.
This "fight" can happen naturally (when our body fights the disease itself) or artificially, for example through vaccination. The more antibodies we have, the better our chances of fighting off the disease.
This "battle" is also fought in biosensors such as antigen or antibody tests. A good antigen detection requires the presence of antibodies in the sensor, and vice versa. And for the most accurate results, we need to know the antigen-antibody affinity.
"Affinity is a parameter that is very important because the more the molecules are related to each other, the higher the sensitivity of the sensor will be, and the more it will be possible to determine whether a person has contracted an infection or a disease from lower concentrations. This will avoid non-specific reactions that can give the wrong answer," explains Dr. I. Plikusienė.
According to the specialist, it is very easy to imagine this affinity:
"We all have close relatives - parents, children, grandparents - whom we want to hug when we meet them. We are happy to see them. And we have, for example, a distant uncle who we see across the street and we don't even want to say hello, because we don't have a very strong interaction... I mean, the better the relationship, the more we want to connect."
It is the same with antibodies and antigens. The more related the molecules are to each other, the more bonds are formed. An antibody is a Y-shaped molecule that has what looks like arms through which it can bind to antigen. If the bond between them is very specific, the molecules will bind tightly. But if not, the parts will either weakly bind together or quickly pull apart.
So if we want to produce an accurate rapid test, we need more closely related molecules."
What are Ieva Plikusienė and her team doing here? Even before the rapid tests are developed, scientists help select which molecules to put in the tests by measuring certain antibodies or antigens to determine their affinity.
As mentioned above, such biosensors are not only applicable to the coronavirus, but also to other biological molecules, such as tumor markers or other diseases, etc. Biosensors have high expectations in drug development, for example in the development of anticancer inhibitors. This is a joint effort with the Vilnius University Life Sciences Center.
(Dr. Ieva Plikusienė. Photo: dr. Remigijus Juškėnas)
Today's and future technology
And what are the means by which antibody-antigen affinities are determined? This is a combined optical and acoustic methods being developed in this research group to understand how coronavirus proteins (antigens) interact with antibodies.
In 2022, I. Plikusienė received international recognition for this research. How does it work?
"The optical method is a technique that uses light to detect interactions between biologically active molecules such as antibodies and antigens. In our studies, we measure the light reflected from a sample when an interaction between an antibody and an antigen occurs on its surface. The measured light is converted into an electrical signal and the result is displayed on a computer screen as the time variation of a parameter. The mass of antibodies or antigens formed on the surface can then be calculated by processing the results of the measurements.
The acoustic method uses acoustic waves to study the same interactions between antibodies and antigens. Here, the parameters of the acoustic waves are measured and also displayed on a computer screen. One of these measured parameters is the temporal variation of the frequency: the fewer antibodies or antigens on the surface, the smaller the variation will be and vice versa. This method, like the optical method mentioned before, also gives an estimate of the mass of the surface, but both can be used in a single experiment to calculate this and other values more accurately," explains the researcher.
Combining optical and acoustic methods to study antibody-antigen interactions is relatively new, she says, as there are not many such tests:
"We are opening up a new field here. Before, we were working only with an optical instrument, but then it became possible to buy new equipment that allows acoustic measurements. This was a strong addition to the work we had done before. We have successfully applied these methods to the coronavirus in a relatively short time, as we already had a lot of experience in this field.
We are now working successfully with biotech companies, helping them to select which proteins are most suitable for the market, for drug development, etc."
The scientist reiterates the multiple benefits of biosensors. Many biomarkers, which are like the fingerprints of a disease, can be successfully detected relatively quickly.
Another global trend is the so-called Internet of Things: the aim is for sensors linked to a person's state of health to "collaborate" with the medical establishment and report on potential risks. For example, if your blood pressure drops dramatically, or your heart doesn't beat as well as it should, you can signal the clinic immediately, etc.
Also ther is an important area that has already been mentioned several times: medicines. With highly sensitive sensors, it is possible to investigate the properties of different preparations that will be used for medicines. "One of the things we are doing is looking at how gold nanoparticles can be used to detect heparin in a joint approach. Heparin is a substance used as a drug to regulate blood clotting. It is most widely used during surgery; it is very important to monitor the amount of heparin in a person's blood so that they do not have too much. So this is also one of the topics we are developing," says Dr I. Plikusienė.
Science will also benefit from llamas
Coronavirus research is not the only area to which the scientist devotes her time and attention. Her working day is very intense, with everything scheduled by the hour. In addition to her work at the FTMC, she has been a lecturer at the Faculty of Chemistry and Geosciences at Vilnius University for 13 years, working as an associate professor, lecturing on physical chemistry and thermodynamics to students at different levels. The latter also helps to study the interactions between antibodies and coronavirus antigens.
"The affinity between antibodies and antigens is a thermodynamic parameter that depends on temperature. If the temperature changes, the affinity may change. Knowing the rate at which antibodies and antigens bind (and the rate at which they are released) can also give us additional information, such as the spatial positioning of the antibody in order to successfully form a complex with the antigen," she says.
Ieva travels extensively for her work, collaborates with foreign specialists and participates in various projects. For example, FTMC is launching a team project to study the interactions of antibodies from llamas (yes, those cute South American animals) with the protein of a "needle" of mutated coronavirus.
It turns out that camelids organisms produce special antibodies that are smaller than those found in humans. This allows them to access, bind to and block the antigen more quickly and efficiently.
"Llama antibodies have great potential in both diagnostics and therapy," says I. Plikusienė. However, you don't have to travel to the llamas yourself - these antibodies are produced in laboratories, so you just need to buy them.
The Department of Nanotechnology of FTMC has a number of partners not only in Lithuania, but also worldwide. The Lithuanian team is working with mathematicians at the Sorbonne University, who are helping to develop mathematical models that allow the antibody-antigen ratio to be evaluated not only qualitatively but also quantitatively.
There is also a collaboration with the European Membrane Institute IEM, based in Montpellier, France: "They have extensive experience in the formation of various nanostructures using metal oxides. We are using such structures in our development of biosensors and bioanalytical systems. These can be nanowires, nanobeams - such as nano-hedgehogs, structures that can be used to develop bio-optical sensors."
Dr. Ieva Plikusienė is also helping the country's young scientists. She is the President of the Young Academy of the Lithuanian Academy of Sciences. This is an organisation that brings together and represents high-achieving Lithuanian scientists under the age of 40.
"We aim to improve the working conditions, position and career path of young scientists in Lithuania. There are many problems related to this. For example, after defending a doctoral thesis, sometimes a scientist does not know what to do next. One of the loopholes is that the stipend for a PhD student is quite high, but after defending the dissertation, the person starts working for a lower salary.
There was also a time when we did not have calls for postdoctoral fellowships. It is important to make that path clear, to provide opportunities - because that is why young professionals simply drop out or rarely choose to do a PhD at all," she says.
Not just a job, but a mission
When asked if she often thinks of herself as doing work that is important to society, Ieva says: "I think scientists are working to make people better off. Maybe we don't communicate enough with the public, because people "pay" us salaries by paying taxes - so we have a responsibility to tell them about what we do and how we contribute to improving their daily lives."
She adds that we probably don't often think that the reason we live so comfortably, so long and so much healthier today than we did 50 to 100 years ago is simply because scientists are doing their job - and developing technologies that can be applied when needed. For example, mRNA vaccine technology has been well-known and developed for decades, even before the rise of COVID-19. Let alone other, "smaller" discoveries that help in everyday life.
"Few people turn on an induction hob in their home and think how much work physicists have put in to make it happen," says Dr. I. Plikusienė.
Written by Simonas Bendžius