Understanding how the microbiome impacts gut motility in autism
Gastrointestinal problems including inflammation are commonly experienced by people with autism although the cause is unknown. Many gene mutations affecting the nervous system, including a missense mutation in the Neuroligin-3 gene, are associated with autism (1). It is now well established that the gut microbiome impacts the immune system and gastrointestinal function.
We hypothesise that Neuroligin-3 mutant mice show altered gut motility which is rescued by treatment with the microbiome-altering drug, AB-2004.
This project will assess the effect of a microbiome-altering drug (AB-2004) on gut motility in Neuroligin-3 mutant mice and inflammation. Mice will be treated with Dextran Sodium Sulfate (DSS) to cause colitis (inflammation of the colon) and the microbiome will be modified using AB-2004. We will use our published video imaging technique (2, 3) to record gut contractile patterns in an organ bath and detect changes in gut function.
This project will identify the effects of modifying the microbiome on gut motility in a mouse model of autism and contribute to designing new therapies for clinical applications.
1. Hosie, S., Ellis, M., Swaminathan, M., Ramalhosa, F., Seger, G. O., Balasuriya, G. K., ... & Hill‐Yardin, E. L. (2019). Gastrointestinal dysfunction in patients and mice expressing the autism‐associated R451C mutation in neuroligin‐3. Autism Research, 12(7), 1043-1056.
2. Swaminathan, M., Hill-Yardin, E., Ellis, M., Zygorodimos, M., Johnston, L. A., Gwynne, R. M., & Bornstein, J. C. (2016). Video imaging and spatiotemporal maps to analyze gastrointestinal motility in mice. JoVE (Journal of Visualized Experiments), (108), e53828.
3. Abo-Shaban, T., Lee, C. Y., Hosie, S., Balasuriya, G. K., Mohsenipour, M., Johnston, L. A., & Hill-Yardin, E. L. (2023). GutMap: A New Interface for Analysing Regional Motility Patterns in ex vivo Mouse Gastrointestinal Preparations. Bio-protocol, 13(19).
Discipline:
Supervisors:
Prof Elisa Hill,
Prof Ashley Franks
Contact: 0434052127, elisa.hill@rmit.edu.au 0477169590a.franks@latrobe.edu.au
Campus: RMIT Bundoora
Program Code: BH058