Dr. Manivannan Subramanian from University of Dayton Awarded $90,000 Knights Templar Eye Foundation Grant for Aniridia Research
Dr. Manivannan Subramanian from the University of Dayton located in Dayton, Ohio was awarded a $90,000 grant for his research entitled: Understanding the genetic basis of miRNA-190/PAX-6 regulation involved in Aniridia, a birth defect in eye.
Aniridia, is caused by mutation(s) in the paired-box-gene-6 (PAX-6) and results in blindness in children. PAX-6 encodes a protein that serves as a DNA-binding transcription factor, which is highly conserved. Dr. Subramanian and others have shown that PAX-6 is regulated by microRNAs (miRNAs). miRNAs regulate gene-functions in various tissues either at transcriptional- or at translational-level. Dr. Subramanian has identified miRNA-190 as a potential candidate in regulating eye phenotype in a forward genetic screen using Drosophila model. He has also confirmed through bioinformatics analyses that eyeless/(PAX-6) is the target of miRNA-190.
His hypothesis is that miRNA-190 regulates eyeless gene expression and any perturbation in this regulation may lead to eye disorders. Studies on eyeless gene mutations in Drosophila have shown either reduced eye or “no eye” phenotype. Aim 1: Regulation of PAX-6 gene expression by miR-190 in the developing eye, and analyzing the function of miRNA-190 by (a) mutating its binding site in ey/ PAX-6 and (b) through miRNA-Sponge or knock outs in the eye development. Aim 2: Regulation of cell proliferation versus cell death by miRNA-190-ey/PAX-6 through JNK signaling pathway in the developmental defects of Aniridia. This study may highlight PAX-6 regulation through miRNA-190 in the eye development and its role in cell-proliferation or cell-death and any dysregulation in this system may lead to Aniridia.