Stable inheritance of genetic information across generations depends on egg and sperm cells acquiring intact chromosomes from parent cells through meiosis. Sorting parent chromosomes into gametes involves programmed formation of double strand DNA breaks (DSB), which is done in the context of structures such as RNA:DNA hybrids (R-loops) that can disrupt processing of the DNA if left unresolved. This project will characterize R-loops and how their presence affects the outcomes of DSB repair during meiosis. The project also aims to improve science literacy by exposing elementary school students of diverse backgrounds to genetics concepts using play and creative exploration. For this purpose, scientists at various career stages will partner with public elementary schools to offer children summer science experiences, including hands-on research. In addition, the project will provide research training opportunities for undergraduates and graduate students in the field of genetics.

The research is focused on processes that perturb genetic stability during gametogenesis. Atypical RNA:DNA hybrid structures are normally formed during meiosis, and chromosomal instability ensues when these structures fail to disassemble. The first aim is to identify mechanisms by which accumulation of these R-loops affects repair of programmed DSBs. The second aim is to examine how R-loops affect crossover formation during recombination. The studies will be performed in the model organism Caenorhabditis elegans and will employ a combination of cell biology, genetic, and genomic approaches. The outcomes of the research will provide crucial insights into cellular processes that regulate genomic stability and, therefore, the integrity of egg and sperm cells.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

National Science Foundation (NSF)
Division of Molecular and Cellular Biosciences (MCB)
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Manju Hingorani
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University of Iowa
Iowa City
United States
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