Project description:Ciliopathies are incurable, pleiotropic diseases that result from defective cilia. Several ciliopathic phenotypes arise from improper processing and activity of Gli transcription factors yet attempts to rescue these phenotypes by overexpressing activator or repressor Gli isoforms have proven unsuccessful. Gli proteins are regulated by Sufu, and Sufu-Gli complexes accumulate in ciliopathies, fundamentally altering the normal Sufu-Gli interaction dynamics. Herein, we investigated whether targeting Sufu-Gli interactions would provide a therapeutic benefit for ciliopathies. We introduced a single copy of SufuD159R, a point mutation that disrupts Sufu-Gli binding, into a ciliopathic mouse model. This genetic modification restored Gli3 binding to DNA and the subsequent transcription of target genes, and led to a significant rescue of numerous ciliopathic phenotypes. These findings suggest that modulating Sufu-Gli interactions may serve as a promising therapeutic approach for ameliorating ciliopathic pathologies.
Project description:To determine whether and how warming affects the functional capacities of the active microbial communities, GeoChip 5.0 microarray was used. Briefly, four fractions of each 13C-straw sample were selected and regarded as representative for the active bacterial community if 16S rRNA genes of the corresponding 12C-straw samples at the same density fraction were close to zero.
