The purpose of the this research is to accurately model human skeletal muscle for high throughput screening. We aim to develop a pre clinical pipeline to quickly screen compounds to discover new therapeutics for muscle wasting conditions. In this project we aimed to measure the muscle wasting that occurs upon cytokine exposure that is associated with chronic inflammation.
Impact
Chronic inflammation is a known contributor to skeletal muscle wasting, particularly in ageing – coined ‘inflammageing’. We are in the process of screening various combinations of cytokines to determine which have the greatest impact on skeletal. The selected mediators of inflammageing will move forward into our 3D tissue models where we can charaterise the molecular events that are triggered to induce wasting and dysfunction.
reNEW research
This project had made significant progress in the last year. We have completed two cytokine screens, one primary, where cytokines were tested alone or in combination with immunostimulant Poly (I:C). Followed by a secondary screen, where we followed up the hits from the primary screen in a pairwise manner. From these screens we have identified ~5 cytokines that induce significant dysfunction in our 2D skeletal muscle models which we will be taking into 3D models in the near future.
Image description
This image shows nuclei (Hoechst/Blue), muscle fibres (Titin/Purple), and mitochondria (Green/ATP5A) following treatment with interleukin-18. Chronic inflammation is known to induce mitochondrial dysfunction and increased oxidative stress.
Credits
Tabitha Cree, Muscle Bioengineering Lab.
