Tools for Studying and Using Small RNAs: From Pathways to Functions to Therapies
Poster Jun 29, 2015
Kenneth Chang and Gregory J. Hannon
During the past decade, small RNAs have emerged as crucial regulators of gene expression and genome function, having roles in almost every aspect of biology. Many small RNAs act through RNA interference (RNAi)-related mechanisms, which involve programming the RNA-induced silencing complex (RISC) to recognize and repress targets. One class of small RNA, the microRNAs (miRNAs), naturally regulates programmes of gene expression. Altered miRNA function contributes to human disease, and manipulation of specific miRNAs is now being pursued as a novel therapeutic modality. Small RNAs have also been adapted for use as tools based on reprogramming the RNAi machinery to silence specific coding or non-coding RNAs. These tools have been exploited to investigate gene function in cultured cells and in living animals. Genome-scale collections of silencing triggers permit phenotype-based genetic screens to be carried out easily in organisms in which they were previously difficult or impossible. Such strategies are being used to discover and validate new therapeutic targets, and small RNAs themselves may offer a mechanism for inhibiting targets that are currently viewed as 'undruggable'.
Characterization of a Type 2 diabetes-associated islet-specific enhancer cluster in STARD10 by genome editing of EndoC-βH1 cellsPoster
Genome-wide association studies (GWAS) have identified more than 100 genetic loci associated with type 2 diabetes. The majority of these are located in the intergenic or intragenic regions suggesting that the implicated variants may alter chromatin conformation. This, in turn, is likely to influence the expression of nearby or more remotely located genes to alter beta cell function. At present, however, detailed molecular and functional analyses are still lacking for most of these variants. We recently analysed one of these loci and mapped five causal variants in an islet-specific enhancer cluster within the STARD10 gene locus. Here, we aimed to understand how these causal variants influence b-cell function by alteration of the chromatin structure of enhancer clusterREAD MORE
P450 Induction in Cryopreserved Hepatocytes from PXR and CAR Nuclear Receptor Knock-out RatsPoster
The nuclear receptors pregnane X receptor (PXR) and constitutive androstane receptor (CAR) are closely related transcription factors that regulate the expression of phase I (cytochrome P450s), phase II metabolizing enzymes and transporter genes in response to xenobiotics, including prescription drugs.READ MORE
Psychiatric Risk Gene Cacna1c and Early Life Stress: Potential Gene-Environment interactions?Poster
Early life stress (ELS) is highly associated with development of psychopathology
and mood disorders in adulthood. Genetic studies have identified variation in the gene calcium voltage-gated channel subunit alpha1C (CACNA1C) to increase risk for several psychiatric disorders. This poster assessed the expression of Cacna1c following prepubertal stress.