A CONVERSATION WITH A SCIENTIST: Olga Dudchenko from Kyiv is a rising star in world science (Part I)
Photo courtesy of Olga Dudchenko
In 2019, Olga Dudchenko, a Ukrainian from Kyiv, was included in the list of scientists Innovators Under 35 according to the MIT Technology Review of the Massachusetts Institute of Technology (USA).
High recognition was brought to her by research in the field of genomics – a section of molecular genetics that studies hereditary material in the cells of living organisms: Olga improved the technology for determining gene sequences – she developed an algorithm that makes it possible to assemble the actual genome of a living organism many times faster and cheaper. For the general public, these are, perhaps, too complex matters.
But the project, organized on the basis of these studies, invariably attracts the attention of the masses: this is the DNA Zoo – a digital database of animal genomes. It looks like a prologue to the events from the movie Jurassic Park. In fact, everything is even more exciting.Olga is, without exaggeration, a rising star in world science, whose works are cited in many scientific manuscripts, whose method allows in a matter of days to collect disparate DNA elements in a single integral genome in the correct order, willingly talks about the intricacies of her work, but avoids talking about personal achievements…
“Genetics, genomics are active areas in modern science, and I managed to integrate into them after moving to the USA. And it is not related to any of my unique abilities. It happened. Let’s see what happens next… What is my mission in science? Do not make me laugh! We do everything we can, but what works, it works,” Olga said in an interview for Huxleў.
GOLDEN PROPORTION OF RANDOMITIES
It will be possible to evaluate my achievements and successes in science only after many years. It’s a common thing: everyone acts according to the power of their abilities, and something comes out for someone in the end. Sometimes it comes easily, sometimes through force. Sometimes you get lucky, and the skills you gain turn out to be successful.
There are people who, from an early age, know what they strive for, what they want. I’m not one of them. I was moving chaotically – a kind of Brownian particle. I chose the path from the landscape suggested by the circumstances. My secret to success?
At the bifurcation point, move very slowly in the hope that someone or something will set the right direction with the necessary strength. This is my whole strategy. Then it is as if you are walking along a bright spacious valley and easily moving forward.
At the moment I am still in the “valley” associated with genetics and genomics, with the assembly of genomes, and, probably, I will stay here for another year and a half. And there it will be seen what bifurcations will arise on the way.
My path in science was determined by a series of happy accidents. First there was a school №145 of the city of Kyiv, Natural Science Lyceum №145, which is on Shota Rustaveli Street. Wonderful place! I got there relatively by accident, and in this accident I was infinitely lucky.
Our family values education, but there were no outstanding scientists among my relatives who would have pushed me towards serious science. Parents have always tried to give me the opportunity to communicate with the best – talented teachers and gifted children.
The first year my classmate was Maryna Viazovska – now a famous mathematician, professor in Switzerland – who solved the problem of packing balls in eight-dimensional space.
After school there was MIPT, Moscow Institute of Physics and Technology, Department of Physics of Living Systems. At MIPT, I defended my PhD, worked in the former laboratory of Anatoly Markovich Zhabotinsky – an outstanding biophysicist and physicist-chemist.
I dealt with the most interesting problem – peristalsis. There are several types of biological pumps in the human body. Everyone immediately thinks of the heart – it is an active pump, centrally controlled.
But there is a different system, for example, the gastrointestinal tract, the lymphatic system, where this pump, let’s say, is distributed – there is no specific organ, a central system that creates high pressure and sets everything in motion.
Such systems respond to impulses locally, the processes are controlled by receptor muscles in a specific area, the systems work in a self-sustaining way, without the participation of the central nervous system.
There is a series of very interesting, spectacular experiments that demonstrate this process. Surprisingly, quite a bit of work has been done investigating the speed of waves in such systems, and I did it. But the research came to an end, and it was necessary to move on.
It was 2012. I discovered that the scientific landscape is such that most areas are shifting in one way or another towards genetics, genomics, sequencing. I think the change in my field of activity and the transition to genetics was to a certain extent also an accident: no matter whoever I chose as a scientific leader, I would still, with the highest degree of probability, find myself in the field of genetics.
The pool of attraction for this area of science is very large and continues to grow. It is facilitated by the pandemic, when the headlines of newspapers talk about the sequencing of the genomes of viruses.
GENETICS – “RUN TOGETHER WITH THE TRAIN”
I moved to the States as a postdoc (research assistant after receiving my doctoral or PhD degree). Physicists and mathematicians’ diplomas are recognized abroad, and you go to work in a US scientific laboratory just like any scientist, say, from Memphis, Geneva…
In the USA, as a physicist, mathematician, I got into a completely different field – genetics, genomics. I found a leader who is passionate about what he does. He readily accepted me, and we plunged into work. There were no far-reaching plans, there was an impulse: let’s start, and what we will do, we will decide on the way.
Now genetics is a very promising field, attractive and inviting. It develops so rapidly and dynamically that people who have devoted years of research to it do not have a great competitive advantage in comparison with newcomers, everything changes hourly, you literally have to “run along with the train”.
There were several reasons for choosing the States. I speak English quite well, it made the move easier. In addition, the United States is a huge country with many universities, colossal investments in science and, it seems to me, more opportunities than in Europe. Plus family circumstances.
My boyfriend (now my husband), with whom we studied together at the Moscow Institute of Physics and Technology, went to work on his PhD dissertation in the States. For five years we have been flying from Russia to the United States and vice versa. But the moment came when we needed to practically solve the problem of reducing the distance between points A and B. And we solved it in several iterations. A common story: modern scientists are a nomadic profession!
DNA SEQUENCING METHOD IN PRACTICE
Since 2017, since the completion of the assembly of the human genome, when this work cost more than three billion dollars, the picture has changed. Collecting genomes became easy, and we launched the DNA Zoo project. It looks simple: we collect the genome of the animal and put it in free access.
The information is mainly used by nature conservation organizations and nature reserves. They are limited in funds and resources, and they cannot carry out such studies, the maximum they can do is perform local sequencing in order to assess the characteristics of the population of animals of interest to them. Thanks to research carried out in 2001-2004, a lot of things have become easier today. The cost of sequencing has significantly decreased, and new generation techniques have appeared.
How does it work in practice? A typical human cell contains 46 chromosomes – 46 very long polymer molecules, DNA, which consist of the letters A, D, G, C … Now there is no technology that allows you to “enter” the cell nucleus and “read” a chromosome from beginning to end. Therefore, we act like this. A bunch of cells are taken, DNA is extracted from the nuclei.
DNA is such long, long “spaghetti”, and when you start taking them out, they break down, break up into small fragments. But there are ways to “read” individual extracted fragments. Using them, like a puzzle, then you need to assemble a whole text corresponding to the sequence of letters of the entire chromosome.
The shorter the section of the “readable text” of the molecule, the cheaper the experiment, but the more difficult the assembly task is. Now work is underway to increase the length of the “text” of the fragment. It is still relatively expensive, but the length of the “text snippets” is increasing, and I think we will be able to read the chromosome from start to finish very soon.
VISUAL LANGUAGE BASED ON HI-C TECHNOLOGY IS OUR MAIN ACHIEVEMENT
Based on the methods developed and published in 2017 in an article in the Sciience magazine, we have created several software tools, visualization tools that allow even when working with the cheapest, very short sequences, to collect genomes up to full chromosomes.
These ideas were not born in 2017. They lined up around the Hi-C technology, which my current leader and co-founder of DNA Zoo Erez Aiden, together with his colleagues, proposed in 2009. It is a method for examining the location of DNA within the nucleus.
The 46 long “spaghetti” are somehow packed in the core, and not randomly packed, but strictly regulated. Certain sequences are always close to each other, some closer to the surface, some inside the nucleus. There is an extremely interesting biology behind all this. Using Hi-C, we read this information relatively easily and cheaply.
And the spatial aspect we have proposed helps in the assembly of the genome. This is roughly the same as starting to assemble a jigsaw puzzle from the side: you can use some geometric information that is not related to the content inside.
We have written many code programs, visualizations, and validations that allow us to investigate special aspects of DNA packaging and use this data to collect DNA in the genome. Gradually, our tools became generally accepted. Now every week we try to upload 1-2 genomes for general use.
The fact that Ні-С-technology could be used in such a way – for assembling small into large – was clear back in 2009, when it was announced for the first time. The question was how to put this assembly into practice. We have developed an understandable algorithm, accessible and clear, and most importantly, we have created a visual language based on technology, that is, we have visualized this process.
This is our main achievement. You can write a good algorithm, you can improve it, or you can teach artificial intelligence to do all this. But it is important to be able to quickly understand whether the result is meaningful.
If we show our principle to a six-year-old child, then he will be able to assemble simple genomes using our visual code and programs. They are intuitive, validation of results is given instantly. Visual languages have always been popular with people.
The visualization is presented in the form of maps. We recently added the ability to visualize maternal and paternal chromosomes separately. A person has 46 chromosomes – 23 pairs of chromosomes from each of the parents. And when genomes are collected, 23 chromosomes are taken – a cross between dad’s and mom’s. In the human nucleus, the chromosomes from both parents are quite close, in other species everything is more complicated.
To be continued…