On Patrol with the Immune System

It is found throughout our bodies, but nobody can see it – not under the microscope, and not even with the help of the most modern imaging equipment. The immune system is a clever complex of cells that has the power to kill us within minutes; for example, during an allergic reaction. It is also capable of granting us a lifetime of good health. Like policemen on watch, its trillions of team members patrol the tissue, organs and blood vessels, and they defend all points of entry in the skin and the mucous membranes against pathogens – as this is where the daily onslaught of viruses, fungi and parasites clamors for entry.

It is this network of messenger substances, receptors and cells that has captured Professor Andrea Ablasser’s scientific heart. At L’Ecole Polytechnique Fédérale de Lausanne (EPFL), the immunologist and native of Bad Friedrichshall in Germany deciphers the immune recognition that is integral to the body’s defense against pathogens. For centuries, generations of researchers have attempted to understand this complex system of defense. Despite considerable success, however, it is still holding on to many of its secrets. Andrea Ablasser, too, is intent on solving the mysteries, and she has come very close to achieving her goal. Her research on the innate immune system has inspired the international scientific community, and it has earned her numerous awards – the most recent being the Eppendorf Award for Young European Investigators 2018, which is awarded annually to extraordinary researchers.

Improving disease treatment

The fact that this much “fun” leaves little room for spare time is not a big problem for Andrea Ablasser. “After all, work for which one is predestined, which is so completely satisfying, isn’t work at all”, she says, and she has another ace up the sleeve of her white lab coat: her partner Tobias Kippenberg, professor of physics, shares her passion for time-intensive research. Time management is therefore not an issue in the Ablasser/Kippenberg household. Science first!

Of Basic Police and Special Forces

Andrea Ablasser is a person of few words. She prefers listening to speaking – unless the topic is science. She then inhales deeply and praises signaling cascades and the talents of cGas and STING. These two molecules are in fact the heart and soul of her research. “Our body’s immune system has developed two mechanisms with which to combat pathogens”, the young professor explains enthusiastically: “non-specific innate immunity and specific acquired immunity.” The innate immune cells do the work of the basic police. They are always on call; they act in the face of danger, and as phagocytic cells or natural killer cells, they eliminate pathogens. If the innate immune system becomes overwhelmed, it will call to the scene the arm of the immune system that the body has acquired over the course of its life – the Special Forces. Their antibodies must be produced first, but once ready, they are then custom-tailored to the enemy.
Within her research project, the scientist and her team of twelve study how the innate immune system recognizes pathogens, and the consequences of such recognition: “We are particularly interested to know how viruses and bacteria are recognized by their DNA inside the cells.” The focus is on a certain signaling pathway that consists of two molecules, cGas and the adapter molecule STING. This signaling cascade inside human cells was discovered only ten years ago. “If both molecules are activated, an inflammatory reaction will result that is important for combating viruses as well as specific types of tumors.”

In some cases, this signaling pathway will start up in error. This is the case when, through stress, cellular aging or illness, the body’s own DNA escapes from the nucleus and the DNA sensors respond in error. Fatal consequences may ensue: “The mistake may lead to a vast number of illnesses such as chronic inflammation, autoimmune diseases and neurodegenerative conditions”, says Ablasser.

Two small molecules with great potential

Based on this knowledge, the scientist has embarked on the search for a substance that suppresses the immune activation. She was successful. “In a screening process involving more than 60,000 molecules, we came across two promising small molecules that were capable of switching off the signaling pathway in a highly specific manner.” The team has been able to demonstrate in human cell lines as well as in mice that this inhibitor is indeed capable of preventing an autoimmune reaction. Andrea Ablasser is hopeful that this inhibitor will be developed further and in the future will be of use in the clinic. “Perhaps for the therapy of diseases of the immune system, but also for the therapy of illnesses which are much more common, such as heart attacks or Parkinson's.” The potential of this inhibitor is now to be tested in a number of different disease models, and Andrea Ablasser has recently co-founded a start-up for this purpose.

Determination and consistency make up the common thread of the life of this resolute scientist. “Even as an adolescent it was my wish to become a scientist.” In high school she skipped a grade and eventually followed the study of medicine at such renowned universities as the University of Oxford, Harvard Medical School and Ludwig-Maximilians-University in Munich. She has come by her enthusiasm for medicine honestly, through her father, chief physician at the hospital in Buchloe in Eastern Allgäu in Germany. “His work fascinated me, and it made a lasting impression on me”, she remembers. In her doctoral thesis, the aspiring scientist focused on immunology, and in 2010 she earned her doctorate in clinical pharmacology.

Living the science

Following her doctorate, she continued her research in the field of innate immunity at the Institute for Chemical and Clinical Pharmacology at the University of Bonn. In 2014, Andrea Ablasser was appointed Professor at EPFL in Switzerland and thereby hit two birds with one stone: the passionate skier was back where she felt most at home – in the mountains. While she no longer participates in downhill ski races, the nature lover gets around on her road bike. Secondly: she no longer has to maintain a long-distance relationship and is able to live with her partner. And what is next? Entrepreneurship in her own start-up instead of science?
“Absolutely not!” Andrea Ablasser remains true to basic science and she can already envision a new riddle that needs solving: the connection between cellular aging and innate immunity. “It is my goal to better understand age-related illnesses such as lung fibrosis or the loss of hematopoietic stem cells.” After all – as her career leading up to today clearly shows – basic understanding of cellular processes is an important step in the cure of disease.

Two small molecules with great potential

The team has been able to demonstrate in human cell lines as well as in mice that this inhibitor is indeed capable of preventing an autoimmune reaction. Andrea Ablasser is hopeful that this inhibitor will be developed further and in the future will be of use in the clinic. “Perhaps for the therapy of diseases of the immune system, but also for the therapy of illnesses which are much more common, such as heart attacks or Parkinson's.”
The potential of this inhibitor is now to be tested in a number of different disease models, and Andrea Ablasser has recently co-founded a start-up for this purpose. Determination and consistency make up the common thread of the life of this resolute scientist. “Even as an adolescent it was my wish to become a scientist.” In high school she skipped a grade and eventually followed the study of medicine at such renowned universities as the University of Oxford, Harvard Medical School and Ludwig-Maximilians-University in Munich. She has come by her enthusiasm for medicine honestly, through her father, chief physician at the hospital in Buchloe in Eastern Allgäu in Germany. “His work fascinated me, and it made a lasting impression on me”, she remembers. In her doctoral thesis, the aspiring scientist focused on immunology, and in 2010 she earned her doctorate in clinical pharmacology.

Living the science

Following her doctorate, she continued her research in the field of innate immunity at the Institute for Chemical and Clinical Pharmacology at the University of Bonn. In 2014, Andrea Ablasser was appointed Professor at EPFL in Switzerland and thereby hit two birds with one stone: the passionate skier was back where she felt most at home – in the mountains. While she no longer participates in downhill ski races, the nature lover gets around on her road bike. Secondly: she no longer has to maintain a long-distance relationship and is able to live with her partner. And what is next? Entrepreneurship in her own start-up instead of science?

“Absolutely not!” Andrea Ablasser remains true to basic science and she can already envision a new riddle that needs solving: the connection between cellular aging and innate immunity. “It is my goal to better understand age-related illnesses such as lung fibrosis or the loss of hematopoietic stem cells.” After all – as her career leading up to today clearly shows – basic understanding of cellular processes is an important step in the cure of disease.