Benchmarking to the Gold Standard: Hyaluronan-oxime Hydrogels Recapitulate Xenograft Models with In Vitro Breast Cancer Spheroid Culture

Many 3D in vitro models induce breast cancer spheroid formation; however, this alone does not recapitulate the complex in vivo phenotype. To effectively screen therapeutics, we urgently need to validate in vitro cancer spheroid models against the gold standard of xenografts. We designed a new oxime-crosslinked hyaluronan (HA) hydrogel, manipulating gelation rate and mechanical properties to grow breast cancer spheroids in 3D. Our HA-oxime breast cancer model aintains the gene expression profile most similar to that of tumour xenografts based on a pan-cancer gene expression profile (comprising 730 genes) of 3 different human breast cancer subtypes compared to Matrigel or conventional 2D culture. Differences in gene expression between breast cancer cultures in HA-oxime versus Matrigel or 2D were confirmed for 12 canonical pathways by gene set variation analysis. Importantly, drug response was dependent on the culture method. Breast cancer cells responded better to the Rac inhibitor (EHT-1864) and the PI3K inhibitor (AZD6482) when cultured in HA-oxime versus Matrigel. This study demonstrates, for the first time, the superiority of an HA-based hydrogel as a platform for in vitro breast cancer culture of bothprimary, patient-derived cells and cell lines, and provides a hydrogel culture model that closely matches that in vivo

Original Data: Hydrogel-mediated co-transplantation of retinal pigmented epithelium and photoreceptors restores vision in an animal model of advanced retinal degeneration

This database contains all the data points used to plot the graphs shown in the 2020 publication by Mitrousis et. al., entitled "Hydrogel-mediated co-transplantation of retinal pigmented epithelium and photoreceptors restores vision in an animal model of advanced retinal degeneration". Please refer to the paper for details

Structural basis for the nuclear export activity of Importin13

Importin13 (Imp13) is a bidirectional karyopherin that can mediate both import and export of cargoes. Imp13 recognizes several import cargoes, which include the exon junction complex components Mago-Y14 and the E2 SUMO-conjugating enzyme Ubc9, and one known export cargo, the translation initiation factor 1A (eIF1A). To understand how Imp13 can perform double duty, we determined the 3.6-Å crystal structure of Imp13 in complex with RanGTP and with eIF1A. eIF1A binds at the inner surface of the Imp13 C-terminal arch adjacent and concomitantly to RanGTP illustrating how eIF1A can be exported by Imp13. Moreover, the 3.0-Å structure of Imp13 in its unbound state reveals the existence of an open conformation in the cytoplasm that explains export cargo release and completes the export branch of the Imp13 pathway. Finally, we demonstrate that Imp13 is able to bind and export eIF1A in vivo and that its function is essential