Although the structure of DNA has already been explored and explained, less is known about molecular regulation of genes, which results the production of proteins and ultimate control of many key biological functions.
Molecular mechanisms that cause eye diseases like cataracts remain particularly unclear.
Salil Lachke, assistant professor of biological sciences at the University of Delaware, is studying cataracts in a $1.95 million project funded by the National Institutes of Health. His research focuses on molecular mechanisms regulating the transparency of the eye lens, The study complements his ongoing cataract studies to better understand the main cause of blindness. Lachke previously developed bioinformatics tools that he used to identify several new cataract-linked genes.
“Out of the estimated 22,000 genes in our cells, a large chunk – about 10 percent – code for proteins that are specialized to bind RNA molecules and control their fate, such as ‘translating’ their information to make other proteins,”Lachke said. “However, very few such proteins have been studied so far, and even fewer have been directly linked to human disease. We think that mechanisms involving these RNA-binding proteins are important for the formation of lenses in embryonic development, and, in later stages, to keep them transparent.”
During the current five-year research project, Lachke and colleagues will investigate the development of the lens and try to understand how specific RNA-binding proteins regulate it. In addition, he plans to development an expanded knowledge-base to better understand cellular pathways and interactions.
A protein called Celf1 that binds to RNA was shown to have an important role in the development of cataracts in mice models.
“It’s an opportunity to learn fundamental new lessons about the molecular basis of how these proteins are involved in controlling RNA information during organogenesis,” he said. “Now we can ask sophisticated questions about which precise letters in an RNA sequence do these proteins bind, and what happens to these RNA messages after the proteins bind them – for example, is the RNA silenced, destroyed, or kept stable for making more protein? We are going to address these questions.”
A recent paper by Lachke, “RNA-binding proteins in eye development and disease: implication of conserved RNA granule components,” published in Wiley Interdisciplinary Reviews: RNA, highlighted the limited knowledge about the field.
“Presently, the only cure to cataracts is surgery,” Lachke said. “Through this study, we hope to understand the molecules that help to make and keep a lens transparent.”
Lachke believes insights from the studies will uncover basic principles in gene expression control and will influence future therapies and prevention.
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