Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Protein engineering extends the language of immune cells

24.01.2019

Evolution of signaling molecules opens door to new sepsis therapy approaches

Small infections can be fatal: Millions of people die each year from sepsis, an overreaction of the immune system. A new immune signaling molecule, designed by a research team from the Technical University of Munich (TUM), now provides the basis for potential new approaches in sepsis therapy.


This the modified human interleukin-27-alpha. Inspired by the murine interleukin-27-alpha, one amino acid has been exchanged, enabling the formation of a disulfide-bridge (marked in red).

Credit: Matthias Feige / TUM


Stephanie Müller and professor Feige in the Laboratory for Cellular Protein Biochemistry at the Technical University of Munich produced a protein, that might be the basis for potential new approaches in sepsis therapy.

Credit: Andreas Battenberg / TUM

The numbers are alarming: According to estimates by the World Health Organization (WHO), around six million people die every year from sepsis. The disease, popularly called "blood poisoning", normally starts with a harmless infection.

If this triggers an excessive reaction of the immune system, the body's own tissue can be attacked and damaged. The overreaction eventually leads to a life-threatening collapse of the body's defenses. In Germany alone, more people die of sepsis than of AIDS, colon cancer and breast cancer combined.

Researchers around the world are on the search for new therapies - so far in vain. An interdisciplinary team from the fields of structural biology, immunology and cell biology has now, for the first time, successfully produced a protein that could balance the overshooting immune response.

The language of immune cells

In their work, the scientists were inspired by evolution: mice are well protected from sepsis by their immune systems. Here, interleukins - messengers, that mediate communication between the cells of the immune system - play a key role.

"The interleukins are the vocabulary with which immune cells communicate," explains Matthias Feige, Professor of Cellular Protein Biochemistry at the Technical University of Munich. The cells form these messenger molecules according to a very specific blueprint of individual amino acids. Their arrangement determines, which three-dimensional structure an interleukin adopts and, consequently, which information it transmits.

Humans and mice have similar, yet different vocabularies. The researchers discovered one striking difference in interleukin-27-alpha. This molecule can be released by cells of the mouse immune system - but not by human cells - and regulates immune cell function.

"Using computer models and cell biological experiments, we discovered that a single structurally important amino acid defines whether interleukin-27-alpha is released by cells of the immune system," explains Stephanie Müller, the first author of the study. "That gave us an idea about how we can engineer novel human interleukin proteins that are released by cells so that we can produce them biotechnologically."

Proteins with new functions from the laboratory

The team then prepared the modified interleukin in the laboratory and tested its biological functions - with very encouraging results: The engineered messenger molecule is recognized by human cells. First analyses suggest that it can indeed balance an overreaction of the immune system, making it a promising candidate for sepsis therapy.

"Our approach allowed us to rationally extend the language of immune cells by engineering a key signaling molecule. This provides us with an opportunity to modulate the reaction of immune cells in a targeted manner. Such a finding was only possible thanks to the close collaboration with immunologists and clinicians from TUM, the Université Sorbonne in Paris and the Helmholtz Zentrum Muenchen," says Feige. A patent for the new protein is already pending.

###

The research was funded by the German Research Foundation (DFG) in the context of the Collaborative Research Center SFB 1035 and the Cluster of Excellence Center for Integrated Protein Science Munich (CIPSM). Matthias J. Feige is a Rudolf Mössbauer Tenure Track Professor and is supported by the TUM Institute for Advanced Study with funds from the Excellence Initiative and the European Union.

Additional funding was provided by the Marie Curie COFUND program of the European Union, the Helmholtz Association, the Studienstiftung des Deutschen Volkes, the Fondation ARC pour la recherche sur le Cancer and the Ligue Nationale contre le Cancer (France).

The research was carried out at the Technical University of Munich at the Department of Theoretical Biophysics (Physics Department), in the Laboratory for Cellular Protein Biochemistry (Faculty of Chemistry), the Center for Allergy and Environment (ZAUM) of the TU Munich and the Helmholtz Zentrum Muenchen, as well as at the Université Sorbonne in Paris.

Publication:

Stephanie I. Müller, Antonie Friedl, Isabel Aschenbrenner, Julia Esser-von Bieren, Martin Zacharias, Odile Devergne, Matthias J Feige:

A folding switch regulates interleukin 27 biogenesis and secretion of its alpha subunit as a cytokine

PNAS, 16.01.2019 - DOI: 10.1073/pnas.1816698116

Media Contact

Andreas Battenberg
battenberg@zv.tum.de
49-892-891-0510

 @TU_Muenchen

http://www.tum.de 

Andreas Battenberg | EurekAlert!
Further information:
https://www.tum.de/nc/en/about-tum/news/press-releases/detail/article/35210/
http://dx.doi.org/10.1073/pnas.1816698116

More articles from Life Sciences:

nachricht Biophysicists reveal how optogenetic tool works
29.05.2020 | Moscow Institute of Physics and Technology

nachricht Mapping immune cells in brain tumors
29.05.2020 | University of Zurich

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Biotechnology: Triggered by light, a novel way to switch on an enzyme

In living cells, enzymes drive biochemical metabolic processes enabling reactions to take place efficiently. It is this very ability which allows them to be used as catalysts in biotechnology, for example to create chemical products such as pharmaceutics. Researchers now identified an enzyme that, when illuminated with blue light, becomes catalytically active and initiates a reaction that was previously unknown in enzymatics. The study was published in "Nature Communications".

Enzymes: they are the central drivers for biochemical metabolic processes in every living cell, enabling reactions to take place efficiently. It is this very...

Im Focus: New double-contrast technique picks up small tumors on MRI

Early detection of tumors is extremely important in treating cancer. A new technique developed by researchers at the University of California, Davis offers a significant advance in using magnetic resonance imaging to pick out even very small tumors from normal tissue. The work is published May 25 in the journal Nature Nanotechnology.

researchers at the University of California, Davis offers a significant advance in using magnetic resonance imaging to pick out even very small tumors from...

Im Focus: I-call - When microimplants communicate with each other / Innovation driver digitization - "Smart Health“

Microelectronics as a key technology enables numerous innovations in the field of intelligent medical technology. The Fraunhofer Institute for Biomedical Engineering IBMT coordinates the BMBF cooperative project "I-call" realizing the first electronic system for ultrasound-based, safe and interference-resistant data transmission between implants in the human body.

When microelectronic systems are used for medical applications, they have to meet high requirements in terms of biocompatibility, reliability, energy...

Im Focus: When predictions of theoretical chemists become reality

Thomas Heine, Professor of Theoretical Chemistry at TU Dresden, together with his team, first predicted a topological 2D polymer in 2019. Only one year later, an international team led by Italian researchers was able to synthesize these materials and experimentally prove their topological properties. For the renowned journal Nature Materials, this was the occasion to invite Thomas Heine to a News and Views article, which was published this week. Under the title "Making 2D Topological Polymers a reality" Prof. Heine describes how his theory became a reality.

Ultrathin materials are extremely interesting as building blocks for next generation nano electronic devices, as it is much easier to make circuits and other...

Im Focus: Rolling into the deep

Scientists took a leukocyte as the blueprint and developed a microrobot that has the size, shape and moving capabilities of a white blood cell. Simulating a blood vessel in a laboratory setting, they succeeded in magnetically navigating the ball-shaped microroller through this dynamic and dense environment. The drug-delivery vehicle withstood the simulated blood flow, pushing the developments in targeted drug delivery a step further: inside the body, there is no better access route to all tissues and organs than the circulatory system. A robot that could actually travel through this finely woven web would revolutionize the minimally-invasive treatment of illnesses.

A team of scientists from the Max Planck Institute for Intelligent Systems (MPI-IS) in Stuttgart invented a tiny microrobot that resembles a white blood cell...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Dresden Nexus Conference 2020: Same Time, Virtual Format, Registration Opened

19.05.2020 | Event News

Aachen Machine Tool Colloquium AWK'21 will take place on June 10 and 11, 2021

07.04.2020 | Event News

International Coral Reef Symposium in Bremen Postponed by a Year

06.04.2020 | Event News

 
Latest News

Black nitrogen: Bayreuth researchers discover new high-pressure material and solve a puzzle of the periodic table

29.05.2020 | Materials Sciences

Argonne researchers create active material out of microscopic spinning particles

29.05.2020 | Materials Sciences

Smart windows that self-illuminate on rainy days

29.05.2020 | Power and Electrical Engineering

VideoLinks
Science & Research
Overview of more VideoLinks >>>