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"It's like the periodic table of the body"

20-year anniversary of Human Protein Atlas

The proteins involved in narcolepsy are shown in this still from a 3D animation
The proteins involved in narcolepsy are shown in this still from a 3D film produced by the Human Protein Atlas.
Published Nov 19, 2020

On the 20th anniversary of the Human Protein Atlas Project, KTH Professor Mathias Uhlén reflects on the journey of this massive database for understanding human biology and helping researchers develop precision medicine.

Each month 300,000 researchers use the open access database, the Human Protein Atlas , which generates about 30 citations daily. This interview with project director and KTH Professor Mathias Uhlén  was edited for length.

Mathias Uhlen in a lab
Mathias Uhlén, Professor of Microbiology

Let's go back 20 years, this all started after the publication of the Human Genome, right?
Exactly, this basically started with the announcement at the White House, in 2000. We started the first pilot project the same year, and we’ve been working ever since to get order and function into what they described.

Order and function, that’s a good way to put it.
The human genome is interesting because it is a blueprint of human beings. But it doesn’t tell you what is going on in the cells. In order to understand human biology and diseases, you really have to go the next level, which is the proteins. The proteins are the building blocks of all life on Earth. So knowing about the proteins is to start knowing about biology, health and disease.

Celebrating 20th Anniversary with Science magazine

cover art of booklet

On the 20th anniversary of the Human Protein Atlas, the project is publishing a special booklet  in the journal, Science, plus the release of a new microsite , a recorded webinar  and a section of the atlas which covers single cell data.

The atlas is regularly updated with new data, which is made freely available to all researcher, and successive sections have been added over time. The latest new feature is the Single Cell Type Atlas . “Chan Zuckerberg Foundation has put a lot of money into single cell technology and it’s a way to not look at tissues, but to look at single cells in tissues,” he explains “We use public data, and we re-analyze this data with our own tools.” Also new is a detailed analysis of the pre-frontal cortex of the brain.

How do you do that?
You have to have a tool, and this tool is the antibody. We have an antibody that recognizes every protein in human beings. It’s a KTH resource and within this resource we have begun to analyze, what are the building blocks? In what tissues are they? Where are they in the tissues, and in the cells? Are they involved in diseases? It’s a little like the periodic table of the human body. Instead of 100 atoms, we have 20,000 genes and proteins.

Of all the studies citing the atlas, which in particular stands out in our opinion?

I think the most important contribution is not a specific sort of thing, but it is more the holistic understanding of the building blocks of the human being. There have been quite a lot of companies that have been started because of the protein atlas. Those of us in the project have started 10 different companies, some of which are in the stock market and doing very well. Just from these startups I know of 10 different studies where the results have been brought into clinical trials with patients. I’m also proud of the holistic sort of Linneaus way of systematically going through all the building blocks of human beings, which is not been done before. (Editor’s note: Carl Linnaeus is the 18th century Swedish botanist who formalized the modern system of naming organisms)

What has surprised you the most about this project?
I’m a little bit surprised about how few proteins we have in the body, how few proteins are secreted to the blood, how few proteins seem to be necessary to keep the human cell alive. We think that only about 10 percent – or 2,000 – of the 20,000 proteins are necessary to sustain human cells. And then the other 18,000 are needed to create the kidney, the brain and different organs. When we started this 20 years ago we were expecting an organ, such as the kidney, to have its own specific set of proteins. But what we found is that there are extremely few proteins which are only used in only one place. Almost all proteins are actually in several places and the elegance of evolution has meant that it’s a little bit like Lego. There are few different kinds of Lego pieces but you can create very complex structures with them, and I think the human body works in the same way. The beauty is not the building blocks themselves, but how they interact and how they form complex structures together.

Does that make it easier or harder to develop precision medicine?
It would’ve been easier for us if the kidney consisted of 100 kidney proteins. But since the proteins are also present in the liver and brain, it makes it harder when you create a drug because you think you’re going to hit a kidney problem but you then also have side effects in the brain. So, it makes it harder but also more fascinating for a scientist. You answer questions, but then you have more questions than you had when you started – which is also the beauty of being in life science right now.

David Callahan

Engineering and life science

The vision of precision medicine involves data-driven life science research, an area where Sweden is leading. “Just a few weeks ago the Knut & Alice Wallenberg Foundation announced that it was funding 3 billion Swedish crowns for data-driven life science,” Mathias Uhlén explains. “And they talk about two things: one, to understand biology, and the other is the possibility to do precision medicine. So their view is to move to the next stage, to use data-driven life science, artificial intelligence and systems biology and then move into understanding and precision medicine. What’s exciting is that the engineering approach is a very good complement to the more medically-oriented approaches.”

The next 100 years of a ‘periodic table’ of the body

Mathias Uhlén refers to the Human Protein Atlas as “a periodic table of the body”, but unlike the periodical table in chemistry, there is no finite conclusion to the work needed to complete the database. “The project is funded for another four years so KTH is committed to continuing at least until 2025. I think this will go on for another hundred years, and I’m hoping that in 100 years it will still be used.”

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