Year: 2017
Type: dissertation
Abstract: The retinoic acid receptor-related orphan receptor gamma, or RORγ, is a member of the nuclear receptor ROR family and its activity can be regulated by the binding of ligands. Our lab has developed an in vivo GFP reporter system, the ‘Ligand Trap’ system, that can be incorporated into the zebrafish genome to identify ligands that target RORγ. I have performed a drug screen, using human RORγ Ligand Trap zebrafish, against a compound library that includes around 4000 natural compounds and approved drugs. 20 hits were identified in the screen, with an antagonist chosen for further characterization: echinocystic acid (EA). Studies were performed to show that EA acts as an antagonist of RORγ by binding to RORγ to inhibit transcription of RORγ target genes. In the future, EA can be used to identify ligand specific cofactors and target genes that are associated with RORγ.
Source: TSpace (University of Toronto)
Author: Rachel Cheuk Lam Sung
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2776816169