Functional dissection of newly discovered cell types in the enteric nervous system

The gastrointestinal tract is uniquely equipped with an own intrinsic nervous system, providing autonomous control of gut physiology.

An even broader significance of the enteric nervous system (ENS) is apparent from its recently demonstrated communication with the immune system and accessory organs.

The vast and heterogenous structure of the ENS has however hampered studies of its specific functions and contribution to disease.

My lab has recently overcome these challenges by transcriptome analysis of single cells and accomplished a molecular classification of enteric neuron subtypes.

In this project we will utilize the unique neuronal signatures to map the intrinsic and inter-organ ENS connectome, and determine the predicted disease vulnerability and functional roles of neuron classes at homeostatic and inflamed conditions.

This will be achieved by combining a new viral-based targeting approach with transgenic mouse technologies, enabling visualization of specific neuron classes and selective manipulation of their activity or gene expression.

Changes in neuro-immune units will be addressed in resected tissue from patients with inflammatory bowel disease and a complementary mouse model.

At sight, our dissection of functional and anatomical features of enteric neuron classes will be instrumental in the development of better diagnostic and therapeutic principles for the many patients suffering from gut ailments with unclear etiology.