Robert D. Nicholls, D. Phil.

Research

My lab uses mouse models and human patients to study the phenomenon of genome imprinting and it’s derangement in human disease. Prader-Willi and Angelman syndromes are disorders caused by a complex defect of genomic imprinting on chromosome 15. The imprinted SNRPN locus is a complex transcriptional unit that encodes the SNURF and SmN polypeptides as well as multiple non-coding RNAs. SNRPN is located within the Prader-Willi (PWS) and Angelman syndrome region that contains multiple imprinted genes, which are coordinately regulated by a bipartite imprinting center (IC). The SNRPN 5’ region co-localizes with the PWS-IC and contains two Dnase I hypersensitive sites, DHS1 at the SNRPN promoter, and DHS2 within intron 1, exclusively on the paternally inherited chromosome. My lab has identified cis- and trans-acting regulatory elements within the endogenous SNRPN 5’ region and allele-specific interactions with multiple regulatory proteins, including NRF-1, which regulates genes involved in mitochondrial and metabolic functions. Our goal is to characterize the complex mechanisms of disease related to these phenomena.