The intestine is much more than a digestive organ as it harbours a complex multitude of cells from various compartments, such as the immune, neural, microbial, stromal, and epithelial compartments. Interactions between these cellular compartments combined with cues from their surrounding microenvironment are crucial in the maintenance of health at local and systemic levels. Using our multi-component organoid models, combined with our fully synthetic hydrogels, atomic force microscopy (AFM)-based stiffness mapping, and multiple particle tracking microrheology, we aim to characterize how neurons modulate matrix remodelling in the intestine.
1. Jowett GM, Norman MDA, Yu TTL, Arévalo PR, Hoogland D, Lust S, Read E, Hamrud E, Walters NJ, Niazi U, Chung MWH, Marciano D, Omer OS, Zabinski T, Danovi D, Lord GM, Hilborn J, Evans ND, Dreiss C, Bozec L, Oommene OP, Lorenz C, Silva RMP, Neves JF*, Gentleman E*. ILC1 drives intestinal and matrix remodelling. Nature Materials. 2021 Feb;20(2):250-259
*co-senior & co-corresponding authors
2. Norman MDA, Ferreira SA, Jowett GM, Bozec L, Gentleman E. Measuring the elastic modulus of soft culture surfaces and three-dimensional hydrogels using atomic force microscopy. Nature Protocols. 2021 May;16(5):2418-2449. doi: 10.1038/s41596-021-00495-4. Epub 2021 Apr 14. PMID: 33854255.
3. Liang Z, Hore Z, Harley P, Uchenna Stanley F, Michrowska A, Dahiya M, La Russa F, Jager SE, Villa-Hernandez S, Denk F. A transcriptional toolbox for exploring peripheral neuroimmune interactions. Pain. 2020 Sep 1;161(9):2089-2106. doi: 10.1097/j.pain.0000000000001914.
4. Ferreira SA, Motwani MS, Faull PA, Seymour AJ, Yu TTL, Enayati M, Taheem DK, Kania EM, Oommen OP, Ahmed T, Loaiza S, Parzych K, Dazzi F, Auner HW, Varghese OP, Festy F, Grigoriadis AE, Snijders AP, Bozec L, Gentleman E (2018) “Bi-directional cell-pericellular matrix interactions direct stem cell fate.” Nature Communications. 9:4049. doi: 10.1038/s41467-018-06183-4in press. doi: 10.1101/2020.04.20.051805
5. Workman MJ, Mahe MM, Trisno S, Poling HM, Watson CL, Sundaram N, Chang CF, Schiesser J, Aubert P, Stanley EG, Elefanty AG, Miyaoka Y, Mandegar MA, Conklin BR, Neunlist M, Brugmann SA, Helmrath MA, Wells JM. Engineered human pluripotent-stem-cell-derived intestinal tissues with a functional enteric nervous system. Nature Medicine. 2017 Jan;23(1):49-59. doi: 10.1038/nm.4233. Epub 2016 Nov 21. PMID: 27869805;.