Two new assistant professors at the University of Bonn are setting out to develop “mini-organs” in order to study metabolic and disease mechanisms. Elena Reckzeh is using these so-called organoids to identify new drug candidates, while Ana Ivonne Vazquez-Armendariz hopes that they can give her a better understanding of lung disease. As Argelander Professors in the Life and Health Transdisciplinary Research Area (TRA), the two researchers are working at the interface between various disciplines—and bridging the gap between chemistry, biology and medicine in the process.
Organoids are made from stem cells in the lab. Cell clusters organize spatially into organ-like structures, which is why they are also known as “mini-organs.” Researchers can use organoids to investigate the interactions between cells in 3D.
The Argelander professorships for early-career researchers (named after the Bonn-based astronomer Friedrich Wilhelm August Argelander, 1799–1875) are geared toward expanding the research profile of the University’s six TRAs, where researchers work together to tackle issues of great relevance to the future across subject and faculty boundaries.
“Organoid research is very much a pioneering field in modern biomedical research,” says Prof. Dr. Waldemar Kolanus, Speaker of the TRA Life and Health and Managing Director of the University of Bonn’s Life & Medical Sciences Institute (LIMES), where the professorships are based. In his view, organoid research is partly about bridging the gap between the existing cell culture models and even more complex animal models and partly about embracing a completely new philosophy: “It’s a question of building living ‘organ-like’ systems from scratch, literally from individual (stem) cells. In other words, constructing organs ourselves rather than ‘pulling them apart’ as we used to will give us a better understanding of how they develop.”
Organoids are already used in numerous labs at the University and the University Hospital Bonn. Says Kolanus: “By recruiting these two Argelander assistant professors, however, we’ve succeeded in establishing a new and highly visible research focus in this rapidly evolving field. We in the TRA Life & Health are delighted about the two young researchers who will be bringing their highly innovative and, most importantly, complementary approaches to the University of Bonn.”
Mini-organs and the hunt for drug candidates
Jun.-Prof. Dr. Elena Reckzeh’s research straddles the boundaries between chemistry and biology. She is aiming to discover novel chemical tools (potential drug candidates), which she intends to use to manipulate biological phenomena and thus understand them better.
Even before she had finished her doctorate, she had already developed a glucose uptake inhibitor in order to starve cancer of glucose, its favorite nutrient. “This made me realize that the biological system we use to discover new chemical compounds can have a major influence on our results,” she says. “Biological systems modeling an organ or disease more accurately will allow us to develop new and possibly better therapeutic strategies.”
Organoids have played an increasing role in Reckzeh’s research work over the past few years. She has used mini-intestines to study the nutrient and drug metabolism inside the small intestine and has deployed tumor organoids to find new strategies for combating squamous cell carcinomas of the head and neck.
As a new Argelander Professor for Organoid Biology, Elena Reckzeh will now be working at the interface between chemical and organoid biology. She and her team mainly want to use organoid models to investigate nutrient uptake in the small intestine and metabolic mechanisms in conjunction with bowel cancer. “We’ll be employing these models in chemical screens to discover new tools for studying metabolic disorders and cancer metabolism,” she explains. By incorporating additional components, including the immune system, microbiota and multi-organ systems, it should be possible to research how changes in the environment affect the disease models.
After studying molecular biomedicine and chemical biology in Bonn and Dortmund, Elena Reckzeh completed her doctorate under Prof. Dr. Herbert Waldmann at the Max Planck Institute of Molecular Physiology in Dortmund. She spent the next few years as a postdoctoral researcher in Prof. Dr. Hans Clevers’ laboratory at the Hubrecht Institute in Utrecht in the Netherlands, where she specialized in organoid research. She received numerous grants and awards, including the Max Planck Society’s Otto Hahn Medal for outstanding early-career researchers as well as scholarships from the Christiane Nüsslein-Volhard Foundation and the Human Frontier Science Program. Her research findings have been published in several high-profile journals.
The lung as a “mini-organ”
Jun.-Prof. Dr. Ana Ivonne Vazquez-Armendariz and her team primarily use 3D lung organoids, which are created from various mouse and human stem cells and are designed to model lung generation and regeneration.
Vazquez-Armendariz has already built a robust and reliable mini-organ in her research work to date, the so-called bronchioalveolar lung organoid (BALO). This is made using cells taken from the epithelial tissue of the lower respiratory tract and stem cells from the connective tissue of mice. The cells organize themselves into lung-like structures within their culture in the space of a few weeks, before diversifying into other cells of the respiratory system. Vazquez-Armendariz and her team developed a technique for introducing immune cells into the lung organoids in order to study how the cells interact while they are being injured and repaired.
“The model is also well-suited to support infection and replication of selected respiratory viruses such as influenza,” Ana Ivonne Vazquez-Armendariz says. This direct method of infection also triggers a stronger antiviral response from the immune cells, allowing Vazquez-Armendariz and her team to imitate lung injury caused by an influenza infection. Her lab also aims to make an organoid from human induced pluripotent stem cells (iPSCs) closely resembling the lung architecture, thus allowing it to serve as a highly informative tool for modeling diseases and be deployed in regenerative medicine.
Says Vazquez-Armendariz: “Ultimately, our research goal is to dissect the cellular and molecular crosstalk between lung epithelium and immune cells. Hopefully this will tell us more about unknown lung development, infection, injury and repair mechanisms.”
Ana Ivonne Vazquez-Armendariz studied clinical biochemistry at the University of Nuevo León in Mexico and molecular medicine at Charité in Berlin. She gained her doctorate and continued her work as a postdoctoral researcher at the Justus Liebig University Giessen. Vazquez-Armendariz established and headed up her first research group at the University of Giessen’s Institute for Lung Health two years ago. She is now continuing the work on lung organoids and disease modeling that she began there in her new position of Argelander Professor at the University of Bonn. Her research has already been published in a number of renowned journals and has won multiple awards, including from the American Thoracic Society.