Insect larvae such as tobacco hornworm can accelerate and economize preclinical research by complementing classic laboratory animals such as rats and mice. Small mammals like mice or rats are indispensable for preclinical research. However, growing ethical concerns led to the incorporation of the 3R principle (replacement, reduction, and refinement) into animal experiments legislation and research funding. In the future, the number of vertebrate laboratory animals should be reduced, and non-vertebrate alternatives should be used where possible. Furthermore, the incorporation of the 3R principle will also economize preclinical research since insect husbandry is much cheaper than the traditional housing of laboratory mammals. In that context, insect larvae like Manduca can serve as an alternative in vivo animal model. Mainly, with the high degree of evolutionary conservation in the innate immunity of the gut and similarities in the enteric epithelial structure, Manduca sexta can serve as a model for human gut inflammation. Recently we employed larvae of the tobacco hornworm Manduca sexta, which are big enough for macroscopic imaging techniques, such as computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET) as a high-throughput platform to study the innate immunity of the gut and host-pathogen interactions. The developed platform represents an ethically acceptable, resource-saving, large-scale, and 3R-compatible screening tool for various life science disciplines, including the identification of new effectors and inhibitors in gut inflammation, the assessment of pesticides or other environmental factors, the assessment and evaluation of new antibiotic therapies, the analysis of host-pathogen interactions, and the identification of new contrast agents or tracers in radiology. Since 75% of the known human disease-causing genes have homologs in insects, this approach will also be helpful in testing preclinical hypotheses in inflammatory bowel disease. Project 1.1 Gut wall thickness measurements Our high throughput approach generates a massive amount of images (e.g., in computed tomography). We are seeking a bioinformatician for help with automatic image segmentation and analysis. To detect gut inflammation, we inject the caterpillars with clinical contrast agents. This helps to detect the gut wall. For the analysis, we need to segment the different gut parts (foregut, midgut, and hindgut) and then measure the thickness of each gut part's gut wall (e.g., with Full width at half maximum measurements). Your task is to develop such a measurement method. Project 1.2 Testing of further imaging modalities. We seek a highly motivated student to test whether additional imaging modalities like ultrasonography or bioluminescence imaging are compatible with Manduca sexta. 1.3 Manduca as a new model for ecotoxicology In 2017, the "Krefeld Study" brought insect mortality into the public consciousness and into the focus of research. The study documented a decline in insect biomass of almost 80% over a period of 27 years. Since then, an intensive search for the causes has been underway. Today, it is clear that there is no monocausal cause for the massive decline in insects. Nevertheless, it is becoming increasingly clear that the mass application of pesticides as part of conventional agriculture has a strong negative effect on insect biodiversity and is one of the main reasons for insect mortality. In this project, we will investigate whether the above-mentioned imaging techniques can be used to document the harmful effects of pesticides on insects. Further reading: •Windfelder, Anton G., et al. "High-throughput screening of caterpillars as a platform to study host–microbe interactions and enteric immunity." Nature communications 13.1 (2022): 7216. •Windfelder, Anton G., et al. "A quantitative micro-tomographic gut atlas of the lepidopteran model insect Manduca sexta." iScience 26.6 (2023). •Koshkina, Olga, et al. "Biodegradable polyphosphoester micelles act as both background-free 31P magnetic resonance imaging agents and drug nanocarriers." Nature Communications 14.1 (2023): 4351.