About This Project

Inflammatory bowel disease (IBD) is a chronic intestinal disease that affects 3 million Americans. Animal models provide significant contributions to dissect the mechanism and develop novel therapeutic strategies. Large-scale and high speed live imaging of intestine can be uniquely performed on zebrafish. We propose to build a novel fish colitis model for studying host-pathogen interaction and drug screening in real-time. With your help, we would love to accomplish these work with our students.

Ask the Scientists

What is the context of this research?

Animal model systems are central to the discovery and development of new and better drugs for the treatment of human disease. The most used animal models in drug screening is the mice. However, mouse models are often costly at large scales, which limit their use in therapeutic screening. Zebrafish, on the other hand, produce thousands of progenies and are cost-effective to house. The transparency of the zebrafish larva allows us to image their gut overtime. We propose to establish live fish quantifiable staining matrices for measuring cell responses . Those matrices will be measured during infection with pathogenic bacteria known to be associated with IBD. We will perform IBD drug screening to evaluate the effectiveness of current IBD treatment.

What is the significance of this project?

Our human IBD genetic data shows that the specific mutations for IBD risk are implicated in innate immune cells and autophagy. Innate immune responses and autophagy are first line immune defenses in the intestine against bacterial infection. With the current colitis mouse and intestinal injury models, the measurement of inflammatory phenotypes usually relies on body weight loss and intestinal length decrease. These phenotype measurements require the accumulation of inflammation and damage over time. We decided to develop a novel method to measure host-pathogen interactions in live animal gut, and further study and validate the function of human IBD mutations and IBD drug response in our new model.

What are the goals of the project?

With the limitation of the current animal models, we propose to build a novel fish colitis model for studying host-pathogen interaction and IBD drug screening in real-time. Our first goal is to establish live zebrafish quantifiable staining matrices with lysosomal pH, autophagy and mucus thickness. Once the matrices is established, we will apply those matrices to measure the effect of bacterial infection in the zebrafish gut. Our final goal is to screen IBD drug using our newly developed zebrafish colitis/injury model.