A CONVERSATION WITH A SCIENTIST: Olga Dudchenko from Kyiv is a rising star in world science (Part II)
Photo courtesy of Olga Dudchenko
DNA ZOO IS A PRACTICAL IMPLEMENTATION OF FUNDAMENTAL RESEARCH
At some point we thought: “Why don’t we do this? We can do it!” A kind of practical implementation of fundamental research. It was the request of time and society. There were many specialists who needed genomes to advance in their scientific fields, they literally begged for various specialized laboratories or companies.
And they puffed out their cheeks and told how difficult it was, and asked for a lot of money for their work. This behavior confused us a lot, because these same companies used our tools that were already laid out in the public domain. And we decided: it’s time to put everything in its place.
Our task was to make the assembly method with the help of Hi-C democratic and affordable. Yes, it is a risky experiment to give away all of your work, but it seems to me that it is currently quite successful. People work with our genomes, conduct scientific activities, publish articles, draw some conclusions… The project is useful.
Why “zoo”? I have a standard triad answer to that. Firstly, animals are cool, they have many different interesting characteristics, skills determined by genetics. It’s great to understand what, where and why. Secondly, we can really help save endangered species. Our partners include many zoos, nature conservation organizations, and nature reserves. How can we help?
Let’s say there is a small population that retains little gene variation. Insignificant variability is often bad: in case of changes in the habitat, the occurrence of infection, almost the entire population is under threat.
The greater the genetic variability, the higher the likelihood of survival of the species, therefore most programs are focused on maintaining the highest possible variability. If you act in a random order, mate close relatives, it will not solve the problem.
When you know that a couple are animals that are not closely related, there is hope to get healthy, high-quality offspring. Actually, the entire set of genetic tests that are carried out for humans are also done for animals. And thirdly, there is a selfish aspect: when you want to know more about yourself, you need to know more about your relatives.
In particular, about their health. Animals are our distant relatives, and understanding their genome will be useful for us, humans. One of the questions that, we hope, animals will help us answer – we are working on it as part of the Encode project – is the search for functionally important elements in the human genome.
Probably everyone has heard about this: a bunch of numbers, a sea of controversy, what is there in our genome “trash”, what is “not trash”, where are protein sequences, where are non-protein… human DNA is large, and not all of us know about it. Knowing the genome of our distant relatives allows us to draw certain conclusions.
Indeed, if the sequence of letters is the same in all mammals – primates, mice, whales – remains unchanged, does not mutate, most likely, it means that it carries a certain functional load. It gives us hints as to which sequences in human DNA are important.
APP FOR THE SEPARATION OF MATERNAL AND PATENTAL CHROMOSOMES
Perhaps, in the near future we will develop new applications, for example, with tools for separating paternal and maternal chromosomes, now this topic is little disclosed. We also work with clinical samples of human DNA, looking for ways to diagnose diseases caused by the breakdown of one of the chromosomes in a pair. In contrast to genome assembly, which has already formed as a separate direction, there are still fewer necessary tools in this area.
Many clinical sequencing companies are showing interest in our work on chromosome separation. Hopefully, in partnership or ourselves, we will do something. But it’s too early to talk about it.
A month ago, our new article was published in Sсience with some developments in this direction. There we collect genomes using the Hi-C method, and latently analyze data on the location of chromosomes in the nucleus. In this article, we consider 24 genomes and show that there are two main types of chromosome arrangement in the nucleus.
In one type, chromosomes occupy separate places, cells, in the cell nucleus and practically do not mix, in the second type they, one might say, are lined up. In this publication, we analyze the issues of chromosome rigidity, we also describe a study carried out primarily by the efforts of our colleagues and co-authors from the Netherlands – an attempt to break this mechanism, transform one type of folding into another. We take a human nucleus, break the stacking order of chromosomes and get something close to the nucleus of a Drosophila.
WE LAID OUT OUR BASE AND THE WORLD WAS DID NOT COLLAPSE!
My boss and I agreed to promote a non-commercial idea. We discussed the issue of founding a commercial company, but first decided to go for an experiment. At that time it was new, unexpected, atypical, similar databases were already published, but with a lot of restrictions for the user.
And researchers need knowledge, they need data to move forward. We are tired of listening to colleagues’ complaints about the impossibility of obtaining the information necessary for work, about the closed nature of research. And we did something radically: laid out our base, just to see what would happen. And the world did not collapse!
Yes, sometimes people publish works on our data without mentioning us, you can’t keep track of everything. We are contacted and asked to process a sample. We never refuse, but we warn that all results will be made public. This condition is usually accepted. I would like to hope that the world is getting a little better from the fact that we allow others to use our best practices.
ABOUT THE NATIONAL SELF-SESSION
I left Ukraine back in 2001, so I spent most of my life outside the country. But my parents live in KYIv, I visit them. Just recently we returned from there – we finally introduced our grandparents to their grandson, who was born during a pandemic. Fortunately, my work and the situation in general does not require me to be determined with this difficult issue, and I am glad of that.
HOW TO MEASURE A SCIENTIST’S SUCCESS
Formally, the success and achievements of a scientist are measured in publications. At least I was taught that when you are looking for a job in the scientific world, no one else is interested in anything other than your articles. And if subjectively… If a person is passionate about his work, if the question he is working on raises him out of bed in the morning, then this is probably a successful scientist – in the sense that he is happy. As much as possible.
Science is an industry not that different from all other industries. The work of a scientist differs little from any other work. There is bureaucracy, there is politics, there is its own structure… Someone more successfully interacts with this structure, someone less.
Interaction is not always correlated with the importance of scientific results. I will cite one example, which has already been discussed many times. A woman scientist for years could not get funding, interrupted somehow, finally went into the industry… And after many, many years she found herself at the forefront of the development of RNA vaccines – an advanced, extremely in demand now, as I think everyone knows, topics…
THE BOOK ABOUT THE GENOME RACE WILL BECOME A BESTSELLER
In America today, genomics and genetics are taking off. It is not known what will happen next, China and other countries are making a lot of efforts in this direction … But so far America is in the lead. People work here with real passion. I think books will be written about this period someday.
As one of my favorites – Microbe Hunters by Paul de Kruif. This is about how in the early years scientists dealt with infectious diseases, about the period from the first vaccine to Pasteur and beyond. About the United States of the late genomic race, one could also write something similar. Of course, a lot has already been published! But there are also materials for the bestseller.
FEELINGS ABOUT UKRAINIAN SCIENCE
Now, probably, Ukraine cannot seriously support genetics and genomics inside the country – experiments are too expensive. Probably need to let people go. Let them go, let them look for their fields and the application of their knowledge. Keeping talented children and counting on the fact that somehow they themselves will create Ukrainian genomics is unrealistic.
Someone, perhaps, will later return in a new status, someone will come for family reasons, there will be some kind of joint projects. It is necessary to give the opportunity and some kind of minimal, but unconditional support to seek oneself. And it’s so difficult, there is no need to interfere. As my former supervisor loved to say, the world is great, God is not malicious. This is a lot, it gives hope.