Applied research cannot do without genome editing

As a little boy he wanted to be a gamekeeper, but eventually his passion for plants won. Plant geneticist Aleš Pečinka from the Center of the Region Haná for Biotechnological and Agricultural Research has moved from classical “flower lover” through cytology to molecular biology and epigenetics. Today he is one of the leading experts in the research of cell nucleus of plants, and, as he calls himself, an ambassador of genetically modified crops. If we, as humanity, want to survive and not burden the environment, we simply cannot do without genetic engineering.

Immediately after graduating from college he left for abroad and stayed there for sixteen years. He did his doctorate in Germany at the Leibnitz Institute for Plant Genetics and Crop Research. Then went to Vienna for a post-doctoral project at the then-established Gregor Mendel Institute for Plant Molecular Biology. “And then I was very lucky to become the head of a research group at the Max Planck Plant Breeding Research Institute in Cologne. These positions are listed for a certain period of time, usually for five years, followed by one or more two-year extension periods,” Pečinka describes his steep career. Already during the extension, he began to look around for opportunities to grow. At that time he contacted the head of the Olomouc workplace of the Institute of Experimental Botany AS CR and the scientific director of CRH Jaroslav Doležel. “The chemistry was just right, and I also knew that the Olomouc workplace is well equipped and the research here is complementary to what I was doing abroad. On top of that, I had family ties here, so it was decided,” Pečinka explains the reasons for returning home, the Czech Republic.

In July, a year has passed since the decision of the European Court of Justice to designate plants subjected to targeted genome editing as GMOs. Scientists from 121 European institutions are calling for a change in regulations. How much do you think this change is needed?
I consider myself one of the ambassadors trying to defend genetic modifications and their meaningful use. In our research we use these methods basically daily in both, the model Arabidopsis as well as cereals. We work with a number of these methods, for example we prepare fusion proteins, usually created by artificial joining of two or more original proteins, we perform genome mutagenesis using molecular scissors CRISPR.

I have been studying these methods in terms of their potential for breeding new varieties or popularization. In my view, these practices will be essential for the breeding of new varieties if we are to provide enough food for the world population, while not burdening the environment even more than now. The methods resulting from the so-called Green Revolution of the last century, i.e. a combination of breeding, use of mineral fertilizers and large amounts of herbicides and pesticides, will not be able to contribute to increase in yields. At the same time, we see that they have a large negative impact on soil quality and landscape biodiversity.

For part of the public, however, this is a controversial and perhaps even complex topic, and there are various myths and concerns about GMOs. So, in your opinion, the fear of genetically modified organisms is inappropriate?
These methods have not only positive impact on yield, but also many other benefits. They enable us to develop plants that can grow in field cultures without large amount of pesticides we are currently applying. The advantage is the possibility of creating plants using new, more efficient fertilizers that will not promote excessive weed growth, thereby reducing the need for herbicides and also limiting the growth of cyanobacteria in watercourses. This will protect the landscape.

Another benefit is the improvement of plant properties with respect to human health. There are already crops with substances important for human nutrition. These include, for example, the so-called golden rice to prevent vitamin A deficiency in the population of poor areas in Southeast Asia, or gluten-free wheat to make life easier for people with gluten-free diet. Of course there is also aversion which is likely to stem from the lack of communication of experts and companies regarding the benefits and potential risks of these technologies.

Unfortunately, environmental organizations also have their share of the blame. They refuse to accept the results of independent scientific research and are in captivity of ignorance and irrational ideas.

I agree that GMO crops must undergo controls before being placed on the market. On the other hand, there are no plausible studies to demonstrate the adverse effects of GM crops on the quality of the resulting products.

If the outdated legislation on GMOs is not changed, could it also have an impact on science?
On the one hand, society wants applied research from scientists, but without genome editing methods we will not be meaningfully able to do so. Or we will create applications to be "put into the drawer", but then the question is whether this is an effective approach. We must also realize that there are countries that are much more progressive in this matter, such as the USA, Canada, China, and Japan will probably review its position very soon. This means that Europe will lose one large field of the economy with great added value. European innovations will not be competitive.

You are often referred to as an expert in plant cell nucleus research. What can we imagined under this term?
Plants do not have a nervous system, many processes are hormone-controlled, and the central control system is, to a certain extent, the plant nucleus where the hereditary information is stored. Many perceptions of the plant come into the cell nucleus, triggering a cascade of molecular reactions to respond to external stimuli or developmental stages of the plant. Thus, genes are switched off and on in the cell nucleus. That is exactly what we are interested in.

That would make the cell nucleus a central part of the plant, something as its “central brain”?
Yes, it is its governing body. There are very few plant cells that can function for a limited time without it. Moreover, the DNA in which the hereditary information is stored cannot be imagined as some spaghetti on a plate, but is wrapped around tiny balls of eight histone proteins, nucleosomes. In human body, for example, about two meters of DNA are wrapped in each cell nucleus in a space with diameter of as little as 20 micrometers. Thus, the cell nucleus controls the cell, and thus the whole plant, but at the same time undergoes a very dynamic process where DNA rearranges, shrinks, and relaxes in various ways. And we are very interested in how it all happens and how it affects the plant.

When your colleagues contributed to deciphering the genomes of wheat, barley or banana tree, was it isolated DNA? And now you need to go further and unravel the tiny balls you mentioned?
For genome reading, DNA is purified from proteins. We are currently trying to use methods to analyze plants inside the cell nucleus. By reading the genome we find out the sequence of four letters of the genetic alphabet – A, C, G, T – and we are able to say with some probability where a particular gene is located in the genome. The next task, however, is to find out what this “text” means for the plants functioning. This is the purpose of studying the cell nucleus. Genome reading can be seen as a necessary basic platform, and now we are trying to decipher this text, giving some meaning to each word.

You are working on several projects, can you describe them closer?
A key topic in our group is so-called Structural Maintenance of Chromosomes (SMC) proteins, which are protein complexes found in all eukaryotic organisms, i.e. plants, fungi, animals and humans. Specifically, there are three – cohesin, condensin and the so-called SMC5 / 6 complex. These complexes are essential for the organization and maintenance of chromosome structure. We focus mostly on the SMC5 / 6 complex, which controls the hitherto unknown way of DNA repair. This research is set within a framework where we try to characterize the functions of nuclear genes that are involved in the organization and management of the cell nucleus.

In order not to be boringly academic, we look at how the properties of the cell nucleus affect properties of plants. In this respect, our core theme is development of seeds, specifically their component – endosperm nutrient tissue. To some extent, it resembles the placenta of mammals. It encapsulates the embryo, nourishes it and regulates its development. We are interested in how the endosperm develops both in the model plant of Arabidopsis, when the embryo eventually consumes the endosperm before germination, and in barley, where the seed is largely made up of endosperm and the embryo begins to consume it after germination. Endosperm cereal is the main ingredient of our food. Flour is produced from wheat endosperm, barley endosperm is important for malt production or as feed. In this case, we combine cell nucleus control with a particular trait that has significant breeding potential.

One of your research directions has a possible overlap into human medicine…
In a model plant Arabidopsis, we discover genes that are involved in repairing a little-known type of DNA damage. We've found five of them so far. All these genes have their homologues (genes of the same type and similar properties inherited from the common ancestor) even in animals. Therefore, we assume that they participate in similar biological processes. Since this DNA damage also occurs in human cells and DNA repair is an evolutionarily conserved process, we assume that the genes identified by us are involved in this process in humans as well. But there is still a long way to go, transferring information from plants to humans is not easy and we are still looking for a partner to test our findings in human cells.

How hard is it to estimate that you are on the right track with research?
To a certain extent, this is possible thanks to learning from previous mistakes. I think earlier failures taught me to design a project so that we do not get into an impasse. But the risk of failure cannot be completely avoided, it is a necessary part of scientific work. At times when something doesn't work for us, we often learn the most. Often it resembles detective work. Science is definitely not boring. One must be largely open to where the road will lead.

You and your colleagues recently published an article in The Plant Cell, when you first described the function of two genes of the SMC5 / 6 complex in plants, namely in Arabidopsis. An unexpected finding was that this complex also affects the development of seeds. You spoke about the importance of basic research. How important is it at a time when applied research and innovations are so accentuated?
Applied research is not possible without basic research, and this is true at several levels. For example, the development of new methods is done on model organisms under laboratory conditions as part of basic research because these models are simple, inexpensive, and easy to control. Only then can the method be applied to other crops or organisms. In model plants, we are able to understand more easily the many processes and mechanisms that take place in plants. This is important, for example, for breeding new varieties.

On the other hand, also in CRH, great emphasis is placed on the transfer of knowledge into practice. The leitmotif of the center´s activities is to help breed economically important crops with desired properties, which will enable them to feed then ever-growing population or produce crops that will have a beneficial impact on our health. How much do you think about this in your daily work?
In everyday work, classical research, we cannot be concerned with having applicable results. Although this may vary from project to project. Our group seeks to push the boundaries of human knowledge, with the idea that somewhere in the distance, our results may be useful in practice. But this is not the primary goal for us. The mission of our institute is to conduct excellent basic research and to develop new methods that will be useful for breeding research.

Max Planck's institutes, where you came to Olomouc from two years ago, tend to be seen as the ideal model - given the results of local scientists, but also in connection with the system of functioning. Working in Germany is a milestone in your scientific career. Is it even possible to move somewhere better from there?
Certainly it is, and I have succeeded in some sense. There are eighty Max Planck's institutes and each of them works a little differently. If I am to compare their environment with my current location, in terms of material equipment, the situation is comparable, in some respects even better. Not only the equipment itself, but also the stability and know-how of the people who operate it. While in Germany we all worked superficially on many devices, in Olomouc there is a different approach and colleagues are more specialized. When a person comes to them, he knows that he is talking to a real expert experienced in a certain method, and that we can do great things together. What is missing in our conditions is about fifty years, when Max Planck's network of institutions went through different periods of development and gradually formed the rules. On the contrary, CRH is basically a greenfield project, and the rules are still being formed.

After your return from Germany, you described the Czech Republic as a country with great potential in science. Have you changed your mind since then?
I am very positive about Czech science because I see efforts to move it forward and make it competitive in the world. Obviously, I am bothered by excessive bureaucracy. Over the past two years, however, we have managed to create a stable and functioning team, for which I would like to thank my immediate supervisor Professor Doležel. I see the strength of the Center of the Region Haná, where we develop cooperation within various departments, between Palacký University, Institute of Experimental Botany, and the Crop Research Institute. There is great synergy, which makes us one of the main centers of plant research in the Czech Republic. If it succeeds to connect with other scientific centers of Palacký University, Institute of Organic Chemistry and Biochemistry AS CR and University Hospital in Olomouc within the planned university institute, the synergy will be even greater.

So you are still planning to stay here permanently?
We have done a lot of work here in two years, a lot of projects are running and a lot of work is ahead. There's no reason to think about moving elsewhere.