Quantifying the activity of cis-regulatory sequences in the hypothalamus using single molecule fluorescence microscopy. (360G-Wellcome-207395_Z_17_Z)

Every cell in the nervous system contains a programme of gene expression that not only determines its morphology and function, but also allows neurons and circuits to respond and adapt to sensory experiences. It is well document that changes in gene expression in response to these stimuli require cis-regulatory DNA sequences (enhancers), which mediate the activation and repression of specific genes. However, how a neuronal network as a whole tunes their transcriptional responses to achieve behavioural changes remain elusive. This project aims to address this by examining how the regulation of the genes arginine vasopressin (AVP) and oxytocin (OT) (neuropeptides that play a role in mammalian social behaviours) can differ between neurons and even gender, by identifying how different enhancer elements contribute to cell-type specific expression. To do this we will combine an enhancer assay with RNA single molecule fluorescence in situ microscopy (smFISH) in the hypothalamus, where these genes are primarily expressed. This will allow us to quantify the activity of specific enhancers in a given context, such as cell type and gender. The results will therefore give an indication of how information is encoded within these enhancer sequences that allows specific expression of the AVP and OT genes.