Transcription
[Music] people laughed, you know, go in your corner, play with your computer, you're useless anyway. So, so that was the attitude in the early '90s. Uh, people became worried. Many people still hated it, but they knew they can't survive without it. Somehow, the world is awash with data on genome sequencing and health. However, harnessing these data requires advanced analytical tools. For more than 30 years, bioinformatician Pier Bor has developed and shared data analysis tools that can help solve problems related to health, the environment, and climate. For this, he is receiving the 2021 Nova Zes Prize.
Growing up in Leipzig in former East Germany in the 1980s meant you could not always follow your dreams. Probably many young people originally wanted to become an architect, uh, but then you see these concrete blocks, very boring, very monotone. So I think almost by chance, I read a book where the photosynthesis was described in molecular terms. It was fascinating. A whole new world in that book, and that's when I wanted to do biochemistry.
Biochemistry is a tedious business. I'm an impatient person, and then I remembered that the computer can help. Pier Bor realized that like buildings, molecules also consist of different types of blocks. A computer could help identify and map these. But that computer was much bigger than a car, and it couldn't divide two numbers properly. You had all these tapes where you have to feed the computer for programming, and Pier Bor's supervisor, Jens, was constantly under starry surveillance. People want me not to do the, the PhD with him because he might end up in prison. So it was a high risk, in a way. But in a way, also high gain because he was a great person, gave me freedom, which I sometimes need, you know, to develop my own ideas.
P. Bor was given the task of optimizing the activity of enzymes by making small changes. By comparing the sequences from the same enzymes from different organisms—humans, pigs, yeast—specific patterns emerged. There were several blocks in there, so one for the co-actor binding site, then the enzyme activity, and then maybe regulatory domain, etc. Then I realized that these co-actor binding sites, which had the greatest potential to prove, they also different kinds of enzymes. So I wrote with a colleague a little program just to find them. And I still remember when we submitted to a journal the first time, uh, one of the reviewers said, it's just a laundry list of these motifs, nobody would ever look at this.
By transferring a more efficient binding motif from one species, the researchers could boost the speed of an enzyme in another organism. So it turned out to be extremely useful. Um, we have, uh, many thousands of users per month, uh, now still. So it's, it's also a bit rewarding that one had the right nose for the right tool at that time.
Like many others in East Germany, P. Bor moved West after the wall fell in 1990. He got a shared appointment at the European Molecular Biology Laboratory in Heidelberg, a university town steeped in tradition in Southwestern Germany, and Europe's flagship laboratory in molecular biology research. If you come from, from East Germany, for the first time, it was day and night, obviously, the way things get handled, plus the culture. People were so much more supportive, and I got stuck because it's indeed fantastic.
During the mid-1990s, with the emergence of the World Wide Web, P. Bor's patent search database was transformed into a highly effective online tool, SMART. The success meant he was sucked into one of history's greatest scientific races and adventures: the Human Genome Project. There was a race, that means in the academic world, because they were a bit under threat from a company, uh, who was much faster moving. They had to team up. The SMART tool became an important tool to help annotate the functions of many proteins that the billions of bases in the human genome encode. You get maybe for 30%, 40% a straightforward answer, and then you have another 30%, you know, but then the rest still had nobody had a clue. So in that particular, for those difficult cases and unknown cases, we could contribute a lot with the tools like SMART, uh, to just annotate, to say what they are.
Soon, P. Bor got invitations from numerous other early animal genome sequencing projects. The many new sequences raised many new philosophical questions, like, what makes a chicken a chicken and not a human? 70% of the genes are the same, even the motifs. So it's only 30% chicken left. We have a bit better taste than a chicken. I mean, we have more taste receptors, but nothing about brain or soul. So basically, the biggest difference is that they have feathers and we have hairs. Although questions like these seem exotic, they are crucial if a researcher or a company wants to induce yeast to produce a certain human protein.
Although genes in a genome can be almost randomly arranged in animals, in bacteria, genes come in pairs or more. This became the first entry point, what we call STRING, to predict which two genes are interacting. But if one gene is continguous to the next one, and there's the third one in a way that comes back to a network. Using tools like STRING, scientists can ensure that all tightly interacting proteins are cloned. To visualize what makes humans differ from chicken or yeast, P. Bor decided to use the gene patterns to visualize the gene and domain similarities. Today, the Interactive Tree of Life tool has more than 20,000 individual users per month and stores more than 1.3 million individual trees.
With a string of very successful tools, P. Bor could easily have lived a very happy research life, continuing what he was doing. But the tools have never been a goal in themselves. Opening new doors, it's more interesting, at least to me. So, so, um, uh, and has with a high risk again, the chance also being really making fundamental new discoveries and a new kind of area. And the computer was always the tool, uh, in a way that could be used.
A new door opened at a conference at which he met Edward Rubin, who was heading up one of the handful of groups in the world that was trying to sequence and analyze thousands of genomes of plants, fungi, and microbes. They sequenced a bit of soil, and they had no clue what to do with that. So they had these snippets, and this is much harder than the Genome Project because the snippets don't belong to one entity, to endless entities. To organize these puzzle pieces into genes and organisms, the researchers had to develop many novel tools to create what are known as metagenomes. It was so exciting because again, it was having real data, the eye opener, what you could do with all this. So whatever we see, not in an organism, but in an environment, this is a footprint of an environment.
Pier Bor and European colleagues decided to investigate one of the least explored but most well-known habitats: the human body. We realized the core of the analysis is that you could stratify the human population into three different groups that we call enterotypes. Although what is normal is still unclear. P. Bor and colleagues then embarked on finding microbial markers for certain diseases. We have quite a few other candidate diseases where we think the microbiome biomarker has a good potential. Pancreatic cancer, for example, where diagnostics is very difficult. You see it too late, and if you see it, it is usually too late. Indeed, the researchers are now developing new non-invasive and cheap early screening tests that complement existing tests. We are probably 70% different in microbial composition, and we know now that the drug response differs. And if we know what's in us, each of us, I think we can tailor the medication much better. And I think that is not science fiction, that is achievable in a reasonable short time scale.
From working with very small protein domains, large genome sequencing projects, and the study of the human microbiome, P. Bor's journey continues onwards to still great goals. This was really an eye opener to go yet another level from the protein to the genome, you know, to the environment, uh, to many genomes, and now we go to the, to the Earth. People laughed about it at the beginning, you know, you're silly, but it turned out and fantastic success.
As part of the Tara Oceans Consortium, which takes samples around the world at depths down to 1,000 meters, P. Bor and his colleagues hope to create a catalog of the ocean biodiversity and study interactions between them to learn how environmental factors such as temperature affect ocean microbial communities. The big questions, what we are up to now, is really, how is molecular functionality evolving on the planet? How is it shared? How is it disseminating? You know, uh, antibiotic resistance, where is it coming from? Those questions, you can suddenly answer with a data-driven approach. And, uh, that's for the remaining years, I think, uh, uh, keeps me busy.
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