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Can we learn to understand how our immune system is activated?

Some proteins are responsible for recognising that a virus has entered our body. Other proteins send information around the body. But how does it actually take place in detail? This knowledge can help save lives.

Professor Rune Hartmann (photo: Lisbeth Heilesen, AU)

There is danger afoot. You have a virus in your body, and your cells need to know that.

However, first of all, your immune system must recognise that it is an enemy in the form of a virus.

These elements of our immune system are central to Rune Hartmann's research. In other words, the recognition that a virus is present and the subsequent communication of the danger to the body's cells.

"Actually, it is a fundamental problem which all organisms are exposed to, that viruses are everywhere. This means that if you intend to be on this earth for more than a short moment, you must also have a way to deal with viruses,' says Rune Hartmann, professor at the Department of Molecular Biology and Genetics at Aarhus University.

It is proteins which are responsible for both detecting viruses on behalf of our immune system and communicating that knowledge around the body.

Rune Hartmann has been working in the field since he submitted his thesis in 1997. The year before, the results of the first experiment to identify the proteins that recognise viruses were published in a scientific journal. The man behind it, the biologist Jules A. Hoffmann from Luxembour, received the Nobel Prize for his work in 2011.

Already in 2004, when “Danmarks Frie Forskningsfond (DFF)” (The Independent Research Fund Danmark) was established under the name “Det Frie Forskningsråd”, Rune Hartmann received the first grant for his research.

Important protein is found in all animals

The earliest research into how proteins recognise viruses and relay this information to other cells was characterised by fragments of information.

"In reality, it was because there were many proteins that could recognise a virus. So they talked into a kind of central communication path. Therefore, the components of this communication pathway were discovered first, while the proteins that had been responsible for the recognition of the virus were only discovered later,” says Rune Hartmann.

In 2013, there was a breakthrough in research. At that time, Zhijian Chen and his research colleagues from China succeeded in identifying the protein cGAS as the main player in recognising that a virus is present in the body.

"Then begins a process where we wonder if cGAS is only found in higher animals. Could it really be?,' says Rune Hartmann.

No, this was not the case. In 2016, the Rune Hartmann started to do study cGAS in the fruit fly (Drosophila melanogaster), from 2020 with support from Danmarks Frie Forskningsfond. Indeed, the fruit fly also turned out to have the protein. In fact, we know today that the systems that can recognise a virus are as old as the first multicellular animals.

Facts: 5 ways to research impact

Danmarks Frie Forskningsfond has presented '5 ways to research impact', which the foundation works on.

Rune Hartmann's work with the proteins which recognise viruses in the body and pass this information on to other cells, respectively, is in line with this strategy.

Among other things, this can be seen in the fact that industry can benefit from an understanding of how the signalling of the presence of viruses in the body takes place. This can naturally lead to the development of new drugs that can take into account which parts of the immune system should be suppressed during an infection.

Furthermore, this can potentially lead to better and more efficient treatment of patients and thus provide savings within the public sector.

Finally, research continuously helps by training PhDs and thus creates a human network of knowledge that industry would otherwise find difficult to access.

Read "5 ways to research impact"  (in Danish).

Facts: grants

Since 2004, Rune Hartmann has received a number of grants from Danmarks Frie Forskningsfond, the most recent of which are:

  • 'Balancing antiviral and pro-inflammatory responses to viral infections', 2020, granted DKK 2,875,366.
  • 'The role of IFN-λ in development and treatment of non-alcoholic steatohepatitis (NASH)', 2017, granted DKK 5,309,587.
  • 'Potentiation of RIG-I signaling by the OASL protein: How does OASL aid RIG-I in initiating an immune response?', 2015, granted DKK 2,528,225.
  • 'Expression of IFNλ4 and its influence on chronic viral diseases', 2015, granted DKK 2,590,742.
  • 'Recognition of viral infections at a molecular level: How the OAS proteins senses intruding viruses and inhibit their replication', 2013, granted DKK 2,333,599.

Our own immune system can put us in danger

For Rune Hartmann and his colleagues, it is now about getting to the bottom of how the recognition of a virus results in other cells being notified.

"We are in the process of putting the fragments of knowledge about cGAS together in a larger context, so that we can actually understand how this signaling takes place. There are several different types of signalling,' he says.

For example, there is a type of signalling which is supposed to help an infected cell try to survive being infected with a virus. Another type must communicate to other cells in the neighbourhood that they should be careful because there are viruses nearby.

A third type of signalling signals that it is time to mobilise the immune system and start producing antibodies.

"So we have a puzzle we need to put together. We must understand the processes on the molecular level, which is clinically very important,' explains Rune Hartmann.

He refers to his work focusing on lung infections. They have the advantage that they are easy to measure in connection with research.

For patients with SARS and influenza, the problems have mainly been created by the patients' own immune system in the form of inflammation.

Inflammation draws water out of the lungs so that you cannot breathe. Therefore, people can drown when they get viral infections.

"It is an important part of the treatment to be able to handle the inflammation. If you are in the risk group and are admitted to hospital with Covid-19, you will be given an anti-inflammatory drug along with some different medicines to try to dampen the viral inflammation. You therefore also have to suppress your own immune system, because otherwise this is what kills you,” explains Rune Hartmann.

The research may lead to new drugs

The researcher hopes that the ongoing research can result in a detailed understanding of the processes that pass on the information about the presence of viruses in our body. From recognition proteins, over signalling proteins to activation of the immune system. The results may gain attention within the pharmaceutical industry.

"We would like to understand how the recognition proteins signal that now you have to start an inflammation, and subsequently now you have to start something antiviral. It's exciting to understand,” says Rune Hartmann and adds:

"It will also have some enormous application possibilities. Because then we can start producing something much more specific medicine, which suppresses the harmful signalling pathways, but keeps the good ones.”

For further information, please contact

Professor Rune Hartmann
Department of Molecular Biology and Genetics
Aarhus University, Denmark
rh@mbg.au.dk - Mobil: + 45 28992578