The enteric nervous system connectome in health and disease

The enteric nervous system (ENS) provides the gut autonomous control of its physiology.

An even broader significance of the ENS is apparent from its recently demonstrated communication with the immune system, microbiota, brain 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 recently overcame these challenges by transcriptome analysis of single cells and accomplished a molecular definition of enteric neuron classes.

In this consolidating project we will utilize the unique neuron signatures to make a comprehensive mapping of the intrinsic and inter-organ ENS connectome.

We will predict disease vulnerability and assess the functional roles of neuron classes at homeostatic and inflamed conditions.

This will be achieved by viral-based targeting approaches enabling visualisation of specific neuron classes, their proximity to executive cells of the gut, synaptic interactions 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 could be instrumental in the development of better diagnostic and therapeutic principles for the many patients suffering from gut ailments with unclear etiology.