Autonomic Neuron Development

The peripheral autonomic nervous system arises from the neural crest. Our laboratory studies the mechanisms controlling the migration of neural crest cells to and within their target tissues, and the mechanisms controlling the differentiation of neural crest-derived cells. The enteric nervous system (ENS) is the largest division of the autonomic nervous system and is crucial for the control of gastrointestinal motility. Our laboratory studies many aspects of enteric nervous system development, including precursor migration, the differentiation of neurons and glia, opportunities for stem cell therapy, as well as the maintenance of the enteric nervous system in the adult gut.

Project Supervisors	Projects
Dr Marlene Hao hao.m@unimelb.edu.au Dr Lincon Stamp lstamp@unimelb.edu.au	Project 1: Examining the relationship between the enteric nervous system and the intestinal epithelial stem cell niche The role of communication between the gut epithelial stem cells and the enteric nervous system remains poorly understood. Epithelial stem cells in the GIT have a remarkable capacity for self-renewal, with up to 1011 epithelial cells being lost and needing replacement every day in humans and so maintenance of the stem cell compartment is critical to gut homeostasis. This project will investigate the novel idea that innervation is essential for the maintenance of the gut epithelia, through interactions with the epithelial stem cell compartment. We will utilise the revolutionary intestinal organoid culture systems combined with enteric neurospheres and perform transcriptomic profiling and functional assays to address the impact of gastrointestinal neuro-epithelial communication in stem cell maintenance during tissue homeostasis. Project 2: Changes in the metabolic activity of enteric neurons, glia and progenitors during development As progenitor cells differentiate into neurons and glia, there are significant changes to their mode of cellular metabolism, which impacts on their fate potentials. For example, in the central nervous system, neurons primarily rely on oxidative phosphorylation for energy, whilst glial cells rely on glycolysis. In this study, you will use different transgenic strains of mice and fluorescent activated cell sorting to isolate individual populations of enteric neurons, enteric glia and progenitor cells. You will then analyse the metabolic profile of each population and how they change during development. Project 3: Benefits of exercise on gastrointestinal health and enteric nervous system function Exercise has been shown to have many beneficial effects for both physical and psychological health, including promoting the proliferation and differentiation of stem cells in the adult hippocampus. In this study, you will examine changes in the enteric nervous system in mice that undergo an exercise regime. Using a new transgenic strain of mice, you will investigate whether there are changes in the proliferation and differentiation of stem cells in the adult enteric nervous system. Project 4: A gut feeling about new therapies for glioma Gliomas are a very aggressive form of brain cancer, with a very poor 5-year survival rate. Gliomas arise from over-proliferation of glial cells, the support cells of neurons, in the brain. Glial cells are also a prominent part of the enteric nervous system in the gut. In this project, you will use a novel line of transgenic mice to investigate gene expression patterns between glial cells in the brain and the gut using RNA-sequencing technology and bioinformatic analysis.

Project Supervisors

Projects

Dr Marlene Hao

hao.m@unimelb.edu.au

Dr Lincon Stamp

lstamp@unimelb.edu.au

Project 1: Examining the relationship between the enteric nervous system and the intestinal epithelial stem cell niche

The role of communication between the gut epithelial stem cells and the enteric nervous system remains poorly understood. Epithelial stem cells in the GIT have a remarkable capacity for self-renewal, with up to 1011 epithelial cells being lost and needing replacement every day in humans and so maintenance of the stem cell compartment is critical to gut homeostasis. This project will investigate the novel idea that innervation is essential for the maintenance of the gut epithelia, through interactions with the epithelial stem cell compartment.
We will utilise the revolutionary intestinal organoid culture systems combined with enteric neurospheres and perform transcriptomic profiling and functional assays to address the impact of gastrointestinal neuro-epithelial communication in stem cell maintenance during tissue homeostasis.

Project 2: Changes in the metabolic activity of enteric neurons, glia and progenitors during development

As progenitor cells differentiate into neurons and glia, there are significant changes to their mode of cellular metabolism, which impacts on their fate potentials. For example, in the central nervous system, neurons primarily rely on oxidative phosphorylation for energy, whilst glial cells rely on glycolysis. In this study, you will use different transgenic strains of mice and fluorescent activated cell sorting to isolate individual populations of enteric neurons, enteric glia and progenitor cells. You will then analyse the metabolic profile of each population and how they change during development.

Project 3: Benefits of exercise on gastrointestinal health and enteric nervous system function

Exercise has been shown to have many beneficial effects for both physical and psychological health, including promoting the proliferation and differentiation of stem cells in the adult hippocampus. In this study, you will examine changes in the enteric nervous system in mice that undergo an exercise regime. Using a new transgenic strain of mice, you will investigate whether there are changes in the proliferation and differentiation of stem cells in the adult enteric nervous system.

Project 4: A gut feeling about new therapies for glioma

Gliomas are a very aggressive form of brain cancer, with a very poor 5-year survival rate. Gliomas arise from over-proliferation of glial cells, the support cells of neurons, in the brain. Glial cells are also a prominent part of the enteric nervous system in the gut. In this project, you will use a novel line of transgenic mice to investigate gene expression patterns between glial cells in the brain and the gut using RNA-sequencing technology and bioinformatic analysis.