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27.01.2021 10:24

Elvira Mass receives the 2021 Paul Ehrlich and Ludwig Darmstaedter Prize for Young Researchers

Jennifer Hohensteiner Public Relations und Kommunikation
Goethe-Universität Frankfurt am Main

The course for organ health is set in the early embryo. This year's laureate has shown that specialized immune cells from the yolk sac accompany organ development and contribute to maintaining their health throughout life. For Elvira Mass, impaired function of these immune cells might cause many diseases.

Frankfurt am Main. Developmental biologist Professor Elvira Mass, Ph.D. from the Life and Medical Sciences Institute (LIMES) at the University of Bonn, receives the 2021 Paul Ehrlich and Ludwig Darmstaedter Prize for Young Researchers, which is endowed with €60,000. The award ceremony in Paulskirche, which is traditionally held on March 14th, Paul Ehrlich's birthday, has been canceled this year due to the coronavirus pandemic. Elvira Mass will be honored next year together with the award winners of 2022.

For organs to stay healthy and functional, they must be constantly surveilled for abnormalities. Until a few years ago, it was believed that this task is performed by immune cells originating from the bone marrow. In a series of elegant genetic labelling experiments, Mass has shown that these cells are mainly yolk sac-derived progenitor cells that migrate to the developing organs, where they immediately differentiate and self-maintain for a lifetime. The reason for their longevity is still a mystery. These immune cells are referred to as tissue-resident macrophages and belong to our innate immune system. Their primary job is to scavenge anything that does not belong to a healthy organ. However, they also produce a broad range of bioactive molecules and growth factors, ensuring that tissues are not only ‘tidy’ but grow, develop, and function.

"The special achievement of Elvira Mass is to have contributed to an important change in perspective when looking at the function of organs," writes the Scientific Council, chaired by Professor Thomas Boehm, Director at the Max Planck Institute for Immunobiology and Epigenetics in Freiburg, in substantiating its decision. “In order to understand how organs develop and what keeps them healthy, one no longer only looks at the bone marrow, but also at the yolk sac and thus at a completely different population of macrophages. This observation has important implications for medicine, because organ-specific defects might be associated with malfunctioning tissue-resident macrophages originally derived from the yolk sac”.

Mass has provided evidence for the health-promoting function of resident macrophages in the mouse brain. Her attempt to manipulate microglia, as the brain-specific macrophages are called, were stimulated by the findings in patients suffering from a rare form of cancer called histiocytosis. This cancer arises from mutated macrophages, which multiply out of control. Many patients suffering from histiocytoses eventually develop neurodegenerative symptoms or behavioural deficits. Mass introduced the mutation typical for histiocytosis specifically into yolk sac-derived tissue-resident macrophages of mice and followed the development of the animals. She found that the mutated microglia cells no longer carried out their traditional tasks but instead attacked and eliminated neurons in their vicinity. Eventually, this led to paralysis demonstrating that mutated microglia can cause neurodegeneration in mice.

With funding recently awarded by the European Research Council, Mass will investigate which environmental factors change the epigenetic imprinting of the yolk sac-derived tissue-resident macrophages and how these changes affect the health of organs. To this end, she will, among other things, examine the influence of nanoplastics on macrophages. Particles that are smaller than 500 nanometers enter the embryo's blood via the placenta and could potentially damage the supporting function of the tissue-resident macrophages.

Short biography of Professor Dr. Elvira Mass
Elvira Mass (34) studied biology at the University of Bonn and did her Ph.D thesis at the Life and Medical Sciences Institute (LIMES) in Bonn. In 2014, she moved to Frederic Geissmann's laboratory at King’s College in London and followed him a few months later to the Memorial Sloan-Kettering Cancer Center in New York. From there she returned to the LIMES Institute in 2017 as a group leader. In 2019, she became W2 Professor for "Integrated Immunology" at the University of Erlangen-Nuernberg. In 2020, she switched to a W2 / W3 professorship at the LIMES Institute. Mass has received several awards, including the Heinz Maier Leibnitz Prize in 2020, which is considered the most important award for young scientists in Germany.

Paul Ehrlich and Ludwig Darmstaedter Prize for Young Researchers
The Paul Ehrlich and Ludwig Darmstaedter Prize for Young Researchers, awarded for the first time in 2006, is conferred once a year by the Paul Ehrlich Foundation on a young investigator working in Germany for his or her outstanding achievements in the field of biomedical research. The prize money must be used for research purposes. University faculty members and leading scientists at German research institutions are eligible for nomination. The selection of the prizewinner is made by the Scientific Council on a proposal by the eight-person selection committee.

The Paul Ehrlich Foundation
The Paul Ehrlich Foundation is a legally dependent foundation which is managed in a fiduciary capacity by the Association of Friends and Sponsors of the Goethe University, Frankfurt. The Honorary Chairman of the Foundation, which was established by Hedwig Ehrlich in 1929, is Professor Dr. Katja Becker, president of the German Research Foundation, who also appoints the elected members of the Scientific Council and the Board of Trustees. The Chairman of the Scientific Council is Professor Thomas Boehm, Director at the Max Planck Institute of Immunobiology and Epigenetics in Freiburg, the Chair of the Board of Trustees is Professor Dr. Jochen Maas, Head of Research and Development and Member of the Management Board, Sanofi-Aventis Deutschland GmbH. Professor Wilhelm Bender, in his function as Chair of the Association of Friends and Sponsors of the Goethe University, is Member of the Scientific Council. The President of the Goethe University is at the same time a member of the Board of Trustees.

Further information
You can obtain selected publications, the list of publications and a photograph of the prizewinner from Dr. Hildegard Kaulen, phone: +49 (0) 6122/52718, e-mail: h.k@kaulen-wissenschaft.de and at www.paul-ehrlich-stiftung.de.

Background on the award of the 2021 Paul Ehrlich and Ludwig Darmstaedter Prize for Young Researchers to Professor Elvira Mass, Ph.D

Conductors from the yolk sac

Immune cells from the yolk sac help embryos to develop properly.

After an egg cell has been fertilized, every step in the development of an embryo must be well coordinated. Heart, lung, liver, and the other organs have to follow their developmental trajectories and all organ-specific cells must follow their respective fate. This year's recipient of the 2021 Paul Ehrlich and Ludwig Darmstaedter Prize for Young Researchers Professor Elvira Mass has shown that this mission is accompanied by specialized immune cells, so-called macrophages that are derived from the yolk sac of the early embryo. Like law enforcement officers, they spring into action when the developmental steps are not on schedule or flawed. Later in life, they contribute to organ health; hence, if these macrophages fail to execute their function, organs might fail too.

Most of the time, new research expands existing knowledge, but sometimes new research results in rewriting the textbooks. Developmental biologist Elvira Mass from the Life and Medical Sciences Institute (LIMES) in Bonn is one of those scientists who has turned existing knowledge on its head. The award winner has revised our understanding of organ development in early mouse embryos. She discovered that most of the macrophages that colonize all growing tissues of the embryo derive from a yolk sac precursor; once in place, they mature together with their organ of residence. For decades, scientists were firmly convinced that tissue-resident macrophages are exclusively derived from haematopoietic stem cells in the bone marrow. Mass has shown that yolk sac-derived tissue-resident macrophages make a life-long contribution to the health of organs; when they don’t live up to expectations, organ functions may fail.

More than a cleaning crew
Macrophages belong to the innate immune system of mammals. They are part of their permanently active surveillance system that, like a radar, constantly scans the body for threats. If the innate immune system encounters a problem, it sounds the alarm and calls the specialized immune system with its tailor-made antibodies and killer cells to the scene. Macrophages work as a cleaning force, remove cell debris and scavenge dead or damaged cells. However, they are more than just phagocytes. Macrophages also produce a large range of bioactive molecules and growth factors. In doing so, they ensure that tissues are not only tidied up, but are also provided with essential support for their morphogenesis. To achieve this feat, each organ has its own set of tissue-resident macrophages. These cells are called microglia in the brain, Kupffer cells in the liver and Langerhans cells in the skin, to name just three examples.

Mass created a map for the differentiation and migration of macrophages in the mouse embryo as the cells progress from their immature stage in the yolk sac to fully developed tissue-resident macrophages in the organs where they live on to adulthood. Apart from phagocytosis, one of their main tasks is in sculpturing tissues and supporting their functions.

If indeed these macrophages are so important for the development and health of an organ, the question arises as to what happens when they or their progenitor cells in the yolk sac are mutated or damaged. Observations in patients suffering from tumours in which the tissue-resident macrophages proliferate in an uncontrolled manner helped Mass in answering this question. Often, these so-called histiocytoses exhibit a specific mutation. Mass introduced this mutation in yolk sac-derived tissue-resident macrophages in mice and monitored the development of these genetically manipulated animals. The ill effects of the mutation were particularly evident in brain microglia, which shifted from a homeostatic to a pro-inflammatory phenotype and began to eliminate neighbouring neurons. Eventually, all mice showed damage to the brain that led to paralysis, indicating that mutated microglia caused neurodegeneration. This finding mirrors the clinical phenotype of patients with histiocytosis who often also develop signs of neurodegeneration or behavioural deficits.

New approach to neurodegeneration
“These experiments show that macrophages with certain molecular changes may contribute to the development of neurodegenerative diseases,” says Mass about her results. "Even though our results currently only pertain to mice, we ask ourselves what these findings mean for the development of neurodegeneration in humans, such as Alzheimer's or Parkinson's disease. In the light of our findings, it is possible that malfunction of microglia, due to mutation or faulty epigenetic imprinting, may contribute to neurodegeneration. I am firmly convinced that, when looking at the development of diseases, we have to pay much more attention to possible malfunctions of the tissue-resident macrophages than before. "

Mass was also interested in the role of macrophages in other tissues, such as osteoclasts in bones. In healthy bones, bone formation and bone loss are in balance. So-called osteoblasts are responsible for building bones, whereas osteoclasts are breaking them down. Mass was able to show that a defect in the growth and differentiation programme of the yolk sac-derived precursors specifically in osteoclasts impairs their function. This leads to an imbalance between bone formation and bone loss, osteoblasts gain the upper hand and harden the bone. In response, mice with a defect in osteoclast formation recruit new macrophages from the bone marrow, a situation that is not possible in patients, in whom germ-line mutations affect all cells in the body, including the haematopoietic stem cells which give rise to an alternative lineage of macrophages. However, a blood transfusion from healthy donors may represent a therapeutic option for these patients, soon be tested in clinical studies.

What could harm macrophages?
In the future, Mass plans to investigate which environmental factors change the epigenetic imprinting of yolk sac-derived tissue-resident macrophages and how these changes influence their function. "I am firmly convinced that many diseases are caused by such changes," says Mass about her research. For example, she wants to study the influence of maternal obesity in mice. Mass speculates that the offspring of overweight mice develop a fatty liver disease due to malfunctioning Kupffer cells. With financial support from the European Union, she will also investigate the influence of nanoplastics on macrophages. Particles smaller than 500 nanometers can pass the human placenta and would therefore be able to damage the support function of yolk sac-derived tissue-resident macrophages during organ development.

Further information
You can obtain the full resume, selected publications, the list of publications and a photograph of the prize winner from the Press Office of the Paul Ehrlich Foundation (c/o Dr. Hildegard Kaulen, phone: +49 06122/52718, email: h.k@kaulen-wissenschaft.de and at www.paul-ehrlich-stiftung.de.

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Wissenschaftliche Ansprechpartner:

You can obtain selected publications, the list of publications and a photograph of the prizewinner from Dr. Hildegard Kaulen, phone: +49 (0) 6122/52718, e-mail: h.k@kaulen-wissenschaft.de and at www.paul-ehrlich-stiftung.de.

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