WG Rossi

Environmental pollution in a dish: Modeling pollution-induced effects on taste and nutrient sensing using tongue and stomach organoids (EpiDish)

This project explores how environmental pollution affects human health by compromising sensory functions, particularly taste perception and nutrient sensing. Air- and foodborne pollutants may disrupt taste and nutrient uptake, potentially impacting calorie intake, appetite regulation, and overall health. To investigate this, the study will combine mechanistic cell-based experiments, sensory trials, and epidemiological studies without relying on animal models. Using human induced pluripotent stem cells (iPSCs), researchers will develop tongue and stomach organoids to model human sensory and digestive functions. These organoids will be exposed to pollutants such as traffic-related particulate matter and heavy metals to assess changes in taste perception, receptor expression, and nutrient uptake. Insights gained from these in-vitro experiments will be applied to a large-scale epidemiological study (NaKo cohort) to explore how urban air pollution affects dietary choices across different age groups. Ultimately, this research aims to enhance our understanding of the impact of pollution on taste and nutrient sensing, promote healthier eating, and improve public health outcomes. The project is funded by the Leibniz Association (competitive procedure). Cooperation partners are the working groups Schikowski, Schins and Staerk, as well as the Leibniz Institute for Food Systems Biology (LSB) in Munich.

Phenotypic variability due to genetic buffering: The role of environmental factors

Genetic factors play a key role in disease development and aging, with Mendelian inheritance patterns representing extremes on a spectrum of genetic variation. However, the effects of harmful genetic mutations can often be mitigated by processes like genetic buffering, which involves mechanisms such as genetic compensation, transcriptional adaptation, and phenotypic plasticity. Though some of these processes are thought to be non-genetic, the influence of environmental factors on genetic buffering and its role in environmentally-induced aging remains poorly understood. In this project, we aim to explore how environmental factors, like air pollutants and food contaminants, affect the expression of modifier genes involved in genetic buffering. Using iPSCs and mutants modeling diseases like Duchenne muscular dystrophy (DMD) and ACTB-associated syndromes, we will expose cells to low-toxicity environmental factors and analyze their impact on modifier gene expression. We hypothesize that these factors, potentially through oxidative stress, will alter gene expression patterns and modulate genetic buffering. We will examine these changes at the epigenetic and transcriptomic level and screen small molecules that may influence environmentally-sensitive modifiers. This work, funded by the DFG and in collaboration with the Haarmann-Stemmann group, aims to provide critical insights into how environmental exposures affect genetic buffering mechanisms.

Small molecules that enhance Prime Editing in therapeutic applications

Genome engineering, a transformative biomedical technology, has gained popularity for disease treatment. While current techniques enable straightforward genome manipulation, achieving precise mutations, especially in in vivo translational applications, remains challenging for both efficiency and safety. Common methods inducing DNA double strand breaks (DSBs) often result in undesired outcomes. CRISPR/Cas-mediated genome editing, specifically base editing (BE) and prime editing (PE), offer alternatives. BE faces challenges such as unintentional deamination and bystander mutations. PE, a newer technique, writes genetic information without DSBs, but its efficiency needs improvement. The lab is focused on identifying small molecules that enhance PE efficiency, identifying candidates for further evaluation in clinically relevant models, aiming to advance gene therapy tools for correcting deleterious mutations in patients. The project is supported by AFM Téléthon.

Quality control of hiPSCs

This project aims to enhance the quality control of human induced pluripotent stem cells (iPSCs), building on previous work that identified new markers for assessing iPSC pluripotency and differentiation potential using long-read nanopore sequencing. The prior study developed “hiPSCore”, a machine learning-based scoring system that accurately classifies pluripotent and differentiated cell states, streamlining the evaluation process and reducing subjectivity. The current project is a direct follow-up, seeking to further improve the quality control standards of iPSCs by refining and validating these novel markers, ultimately enhancing the reliability and clinical utility of iPSCs for research and therapeutic applications. The project is funded by NRW.