Dr. Lorenzo Bonaguro from the German Center of Neurodegenerative Dieseases (DZNE) has been awarded a Starting Grant from the European Research Council (ERC) totaling about 1.5 million euros to investigate the influence of the ubiquitous PFAS chemicals on the immune system. His research will utilize so-called organoids and cutting-edge analysis methods.
Since their invention in the 1950s, thousands of different substances from the category of per- and polyfluorinated alkyl compounds (PFAS) have been developed. Due to their water and fat-repellent properties they are used in countless products like cosmetics, medical devices, clothes and anti-adherent coatings. In addition to their basic chemical structure, the compounds have something else in common: They are almost unbreakable and therefore referred to as “forever chemicals”. Given the widespread presence, their impact on humans is much discussed. “PFAS have been found in the blood of people and there is evidence that chronic exposure even to low levels can pose a health risk, because these chemicals tend to accumulate in the organism,” explains Dr. Lorenzo Bonaguro, a scientist working in DZNE’s “Systems Medicine” research area. “Therefore, I want to assess how PFAS affect the immune system, which is crucial for human health. In fact, I suspect that these chemicals may interfere with the function of the immune system and prevent it from responding appropriately to hazards.”
Focus on low levels
Existing toxicity screenings mostly examined the acute effects of high PFAS concentrations. In view of this, the Bonn scientist wants to break new ground. “My research will focus on the effects of low, allegedly harmless concentrations over longer periods of time. This aspect is largely unexplored. PFAS are the subject of much debate. I would like to contribute to resolving the current controversies with reliable data,” he says. “This project can help understand and better manage the effects of PFAS. It could also contribute to new approaches for testing the biological activity at low concentrations of other pollutants.”
Tiny tissue samples
The project is based on studies of “organoids” derived from human secondary lymphoid organs, such as tissue from tonsils, and on studies in mice. The research will be undertaken by Bonaguro with a handful of collaborators. “Our organoids are tiny, albeit highly complex tissue cultures that reproduce key features of the human immune system. In particular, they allow to study the behavior of so-called B cells and T cells, which are essential components of the adaptive immune system.” These organoids and also the mice will be exposed to different types of PFAS. “We will explore PFAS-related alterations down to the molecular level. For this, we apply advanced methods such as single-cell transcriptomics. This technology allows to generate a kind of molecular fingerprint of the immune cells reflective of status of individual cells. This generates enormous amount of data that we will analyze with modern bioinformatics approaches.”
Reaction to antigens
Bonaguro’s interests include which immune cells are most sensitive to PFAS and whether these chemicals hamper the ability of immune system to respond to “antigenic stimulation”, that is, to substances that are foreign to the organism. This response is critical for both the functioning of vaccines as well as for fighting pathogens. “We will also study potential measures to combat negative impacts and examine whether long-term effects persist after PFAS have been removed from the environment,” the scientist says. “Taken together, the project will provide a comprehensive overview of the consequences of PFAS exposure. In the long term, beyond the current project, I would like to validate these studies in humans.”
