Deciphering the Intestinal Pathophysiology of Cryptosporidium Infection in a Neonatal Mouse Model: A Multi-Omics Approach

• Applicant: Professor Dr. Philipp Olias
• Subject Area: Parasitology and Biology of Tropical Infectious Disease Pathogens
• Term: since 2026
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 572436598

This research project is dedicated to unravel the complexities of cryptosporidiosis, a severe diarrheal disease that primarily affects young children and is caused by microscopic Cryptosporidium parasites. Despite its significant impact, resulting in more than 120,000 child deaths annually in the Global South, the molecular mechanisms that lead to the medical problems in the intestines of young patients are poorly understood. Using cutting-edge technologies such as single-cell RNA sequencing, spatial transcriptomics, and digital pathology, our study examines the intricate host cellular changes in the small intestine of neonatal mice as a model of Cryptosporidium infection in children. In doing so, we aim to understand the complex microscopic world inside the gut, using advanced tools to guide us through this exploration. At the same time, we are looking closely at specific proteins that the parasite releases into the host cell, identified by targeted proteomics. We expect these proteins to act as tiny keys that the parasite uses to manipulate and control the intestinal cells it infects. Our three main goals are: (1) To study when and where gene expression changes occur during Cryptosporidium infection using single-cell spatial transcriptomics. This is like making a time-lapse video of activity in the gut during infection, helping us understand the precise moments and locations where things go wrong. (2) Verify and describe a secreted Cryptosporidium protein and find out which host proteins it interacts with. We think of this as identifying the tools the parasite uses to disrupt the normal functions of children's intestines. (3) Understand how the identified Cryptosporidium protein affects host gene expression and gut health. This is critical to discovering the specific ways in which the parasite's tools cause damage and help us develop strategies to stop them. The successful completion of this research project is expected to significantly improve our understanding of cryptosporidiosis and provide a solid foundation for more targeted interventions, such as treatment and prevention, in the near future. Integrating advanced techniques and AI into morphological analysis is like going from a blurry photo to a high resolution image, giving us a clearer view of what's happening inside the gut. Identifying key parasite proteins that influence host gene expression could be a breakthrough in understanding this diarrheal disease, much like finding a crucial puzzle piece that helps complete the picture. The detailed atlas of the infected small intestine generated by this study is expected to be a valuable resource for future research, providing a roadmap for scientists to explore the intricate interactions between the parasite and the host. These findings have the potential to foster collaboration across multiple fields and contribute to much-needed interventions against this devastating childhood disease.

• DFG Programme: Research Grants