Research Projects

Spinocerebellar Ataxia 8 (SCA8) is a neurodegenerative disorder caused by CTG repeat expansion in a non-coding 3' end of non-protein forming RNA. Researchers have used a Drosophila model to study the molecular genetics underlying SCA8 and identified several RNA binding proteins (RBP) that can modulate the disorder. Spoonbill RBP, which houses a KH RNA binding domain, is found to suppress SCA8-associated neurodegeneration and motor problems. It also forms a ribonucleoprotein complex with expanded SCA8 RNA and depletes expanded pathogenic SCA8 transcripts. Depleting the normal pool of Spoon protein results in enhanced impairment and degenerated photoreceptor neurons. To better understand the molecular mechanism underlying Spoonbill mediated rescue of SCA8-associated neurodegeneration, researchers plan to use various approaches to unravel the basic mechanism of SCA8 pathogenesis. They also aim to gauge the implications of these mechanisms for other non-coding RNA expansion disorders like myotonic dystrophy using established Drosophila models. A 67kDa protein, Larp7, has been identified that physically interacts with Spoon and is present in the Spoonbill SCA8 RNA-protein complex. The researchers plan to perform whole RNA sequencing of SCA8 in combination with Spoonbill and identify interesting candidates that can possibly modulate SCA8 at the systemic or specific cellular level. They hypothesize that both normal and expanded non-coding RNA sequester different sets of RNA binding proteins and regulate them.