CircHtt in brain development and Huntington`s Disease: elucidating in vivo brain functions of a novel circular RNA molecule stemming from the Htt locus

ongoing

I am a neuroscientist specialized on brain development and genetic brain disorders. During my PhD with Dr. Gaia Novarino (IST Austria) I developed a strong expertise in using in vivo mouse models and a large number of different techniques to investigate the underlying cause of intellectual disability and autism. My work helped to better understand the pathophysiologic mechanisms driving these complex neurodevelopmental conditions, as well as the process of brain development more in general. Now, I aim to expand my research profile to neurodegeneration and the non-coding genome, specifically circular RNAs (circRNA). As a postdoctoral researcher in the lab of Dr. Biagioli at Dep. CIBIO (UniTN) I seek to combine my strong background in functional in vivo studies with her outstanding expertise in Huntington`s Disease (HD) research and epigenetics to elucidate a novel regulatory pathway in HD. In this proposal, I designed a dedicated research and training plan that will significantly expand my scientific portfolio and uncover the in vivo functional role(s) of circHTT, a newly discovered circRNA molecule -discovered and initially characterized by Dr. Biagioli’s lab - stemming from the HD locus. We will study its mouse orthologue, circHtt, focusing on expression dynamics and pattern during development and aging and visualize its cellular and subcellular localization in the brain. We will analyse its relevance for HD pathology by using HD mouse models and uncover its molecular brain function(s) by exploiting the innovative and highly specific CRISPR-Cas13 knock-down machinery in vivo. The results of this project will highlight a novel regulatory network in HD pathophysiology in which circHTT may act as modifier of/or novel biomarker for HD progression, or represent a novel molecular drug target. This award is vital for me to return from maternity leave and join the Biagioli group. It will significantly contribute to my career perspectives inside and outside of academia.