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Beyond the Genome

We talk to the winner of this year’s Akzo Nobel Science Award about his groundbreaking project to map all 22,000 proteins in the human body.

We talk to the winner of this year’s Akzo Nobel Science Award about his groundbreaking project to map all 22,000 proteins in the human body.

the human genome was successfully sequenced four years ago, it was hailed as the biological equivalent of putting a man on the moon.

So when Akzo Nobel Science Award winner for 2005, Professor Mathias Uhlén, recently described that remarkable achievement as “not that useful,” it came as a bit of a surprise to say the least.

But far from being flippant, Uhlén was simply trying to put things in perspective. As the man behind a pioneering project to map the human proteome, the highly respected Swedish scientist was merely trying to point out that the genome project simply nudged the door open, now the real medical revolution can take place.

“For most scientists, the genome project is not that useful,” he says. “What is useful is that someone else has now been able to come in, take all the genes and map them as proteins. So genome paved the way and now the real value is being created.”

The work being carried out by Uhlén and his team has massive medical implications. Their research project—known as the Human Proteome Resource (HPR)—is systematically mapping the full set of human proteins, the building blocks of life.

Once the work is complete, they will have created a so-called protein atlas of all 22,000 human proteins, which will not only increase the understanding of how the body works, but also boost the capacity to address disease through the development of new treatments and drugs.

Targets
“If you go to a pharmacy today, about 98 percent of the drugs are directed to proteins,” explains Uhlén. “All the drugs in the world are directed towards about 500 proteins. Obviously, what I hope is that our work will help us to define all the future targets for all future pharmaceuticals. Not only that, but if we can also see how every protein is expressed in different parts of the body, then it should be possible to predict if a drug will give side effects or have adverse effects.”

The possibilities, therefore, are staggering. Because by mapping the proteins in the body, scientists will be able to understand the human body and disease in a way that was not previously possible. It will provide a better understanding of when/where proteins are active (brain, heart, liver, kidney and so on) and which/how these proteins interact with each other in complex networks.

Also, by identifying proteins in a blood test, doctors will, for example, be able to use the protein atlas to help identify different types of disease and see which organs are affected. So a cure for some forms of cancer is not only possible, but probable.

“I would be very disappointed if we didn’t have several cancer therapies coming out of this,” states Uhlén. “The research tools will be available right from the point when we release the protein atlas. The diagnostic tools take five years to develop and the pharmaceuticals take 15 to 20 years, so it’s a long way off.

But cancer therapy in most cases is very crude and what we all want to have is more specific molecular applications, more personalized cancer therapies. So I hope our work will pave the way for personalized medicine, especially in cancers, but also in Alzheimer’s and diabetes for example.”

Antibodies
Funded by the Knut and Alice Wallenberg Foundation, the HPR project is being carried out at the Royal Institute of Technology in Stockholm, Sweden (where Uhlén is based) and Uppsala University, also in Sweden. Around 100 people are involved, with their work (which mostly involves making antibodies for every protein) having started way back in the early 1990s.

“I was involved in the genome project at the time, doing a lot of sequencing and mapping,” says Uhlén. “Coming from a background as a protein chemist, we decided to try and see if we could map proteins in a more systematic manner. It took us almost ten years to sort things out, but then in 2001/2002, we thought we had a technically feasible system and that’s what we started in the summer of 2003.”

He goes on: “We estimate that we have about 22,000 human proteins and what we are trying to do now is scale-up so that we can more or less analyze 3,000 of these every year. That means in four or five years we’ll have mapped about 75 percent of all the human proteins.”

The first major landmark was passed on March 15—the same day he received his Science Award from Akzo Nobel CEO Hans Wijers—when the first 200,000 images (representing around 400 proteins) were released to a select group of international researchers.

The next major step will take place on August 29 at the Human Proteome Organization Conference in Munich, Germany, when the database will be made available to the general public. The plan after that will be to release an additional 500,000 images, representing around 800 proteins, every six months.

It goes without saying that the HPR project is producing mind-blowing amounts of data—about 150 gigabytes every day—and there have been some operational problems along the way. But sophisticated data storage technology is being used to handle the wealth of information being produced, which is drawing on expertise from fields such as bioinformatics, genetics, medical engineering and advanced image analysis.

“We are producing about 4,000 new images every day now and simply looking at them and knowing that these proteins are something that everyone in the world has—but we’re the first ones to actually look at the images and see where they are—it’s a fantastic feeling,” enthuses Uhlén.

“I didn’t dare to think that this would be possible. Only after the genome project defined all the genes did it become possible to do it on this sort of scale.”

(Published: April 6, 2005)

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