Physics Colloquium: Investigating the Gut-Brain Axis and Neurodevelopmental Disorders using Soft Matter Rheology

Physics Colloquium
Investigating the Gut-Brain Axis and Neurodevelopmental Disorders using Soft Matter Rheology

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(Note: Dr. Jensen will be presenting remotely but her talk will be broadcast in 1125 Carlson – please try to join us there if you are able!)

Dr. Mikkel Jensen
Associate Professor, Dept. of Physics and Astronomy
Cal State, Sacramento

Event Details: Your intestines are home to a range of symbiotic bacteria essential to your health. This so-called gut microbiome affects human brain and neuronal development and may contribute to the pathophysiology of neurodevelopmental disorders. However, it is unclear how risk genes associated with such disorders affect gut physiology and how the mechanical properties of the gut tissue might play a role in gut-brain bidirectional communication. We study a particular gene in the fruit fly Drosophila Melanogaster, “kismet,” and its link to the gut-brain axis. Kismet is an orthologous gene of chromodomain helicase DNA-binding protein (CHD) family members CHD7 and CHD8, which are known risk genes for neurodevelopmental disorders with co-occurring gastrointestinal symptoms in humans. We use flies with a null mutation in kismet and find that mutants exhibit a significant increase in gastrointestinal transit time, suggesting functional homology between kismet and vertebrate CHD7/CHD8. Metagenomic sequencing further reveals reduced diversity and abundance of gut microbiota across all taxonomic levels. Additionally, behavioral assays show decreased neuronal function, indicating that the kismet mutation disrupts both gut microbiome composition and neural activity. To investigate whether the kismet mutation also affects gut tissue mechanics in the flies, we dissect whole gut tissue from both kismet mutant flies and control flies. We quantify the tissue mechanics using extensional rheology and find significant changes in both the mechanics of kismet mutant gut linear elasticity, strain stiffening behavior, and tensile strength. Hence, we propose that kismet influences gastrointestinal phenotypes that contribute to the gut-microbiome-brain axis to influence behavior. We suggest that gut tissue mechanics should be considered as an element in the gut-brain communication loop, both influenced by and potentially influencing the gut microbiome and neurodevelopment.

Bio:  Mikkel Herholdt Jensen is an associate professor of physics at California State University, Sacramento. He completed his B.S. in physics and mathematics at the University of Southern Denmark in Odense in 2005 followed by research at the Center for Membrane Physics (MEMPHYS). He earned his PhD from Boston University in 2013 where he focused on investigating the biopolymer actin and the regulation of actin mechanics and dynamics by smooth muscle actin-binding proteins. He was a postdoctoral fellow at Harvard University continuing work on cytoskeletal polymers and cell mechanics before joining the Department of Physics and Astronomy at California State University, Sacramento, in 2015. Mikkel’s current research interests include soft matter rheology, thermodynamic driving forces in biomimetic systems, cells, and tissues, and their relation to health and disease. He was recognized with his College’s Outstanding Faculty Award for Teaching in 2021 and is active in physics education research investigating active learning modalities and their efficacy in improving equity and student success in undergraduate physics.

Intended Audience: All are Welcome!

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