Research Grant Award

Research Fellowship Award

Qurashi, Abrar, PhD

Emory University, Atlanta, GA
Understanding the molecular basis of rCGG mediated neurodegeneration in Drosophila melanogaster

Fragile X tremor ataxia syndrome (FXTAS) is a neurological disorder that causes tremors, balance problems, difficulty in walking, dementia and mental changes in males usually after age of 50. The underlying defect for this neurological disorder is the gene FMR1 responsible for fragile X syndrome, the most common inherited cause of mental retardation. In FXTAS, unlike fragile X syndrome, FMR1 gene produces a toxic messenger RNA because of the abnormally high numbers of the repeating DNA sequences (55-200 CGG units) called premutation. Modeling the FXTAS disease in Drosophila has shown that a particular group of RNA binding proteins in the brain are sequestered by these toxic messenger RNAs, thereby preventing them to perform their normal function. Among the sequestered proteins is Pura that is particular because loss of Pura in mice produces FXTAS like symptoms, suggesting important role for Pura in the disease mechanism of FXTAS. This project proposal is aimed to understand the cellular and molecular pathways affected due to sequestration of Pura in the brain because of toxic messenger RNA. This proposal is also aimed to utilize Drosophila FXTAS model for screening FDA approved small molecule libraries for potential therapeutic intervention for future use in humans.