With the grant, Cornell University has established a new Center for Reproductive Genomics (CRG), joining a national network of similar centers connecting basic and clinical reproductive scientists. Starting this month, the CRG will investigate how a recently discovered class of molecule called “small RNA” influences meiotic errors – the genetic basis of reproductive disorders and birth defects. The team will translate basic research discoveries into clinical innovations to help diagnose and treat infertility and birth defects.

“Humans face higher rates of reproductive problems than most other species,” said CRG Director Paula Cohen, professor of genetics at the College of Veterinary Medicine. “My lab focuses on human eggs and sperm, which are prone to chromosomal abnormalities causing birth defects such as Down and Klinefelter’s syndromes. Other CRG researchers work on issues with sperm, or basic cell biology influencing reproduction.

“Since eggs and sperm will give rise to the next generation, it’s critical to understand how aberrations in them occur,” she said. “Our center aims to learn how and why these problems happen, why they arise in humans more than in other species, what small RNAs have to do with it, and ultimately what we can do about it.”

DNA in genes encodes RNA, which usually makes proteins. However, about 15 years ago, investigators identified smaller RNAs that did not make proteins. Instead, these small non-coding RNAs interfere with the DNA-to-RNA-to-protein production line, regulating whether and how genes are expressed. Our cells are packed with them, but germ cells – eggs and sperm – have unique small RNAs that other cells lack.

“Our center studies how these small RNAs influence egg and sperm production and how this affects human fertility,” Cohen said. “We will take these questions from the lab all the way to human medicine, conducting basic biology research in Ithaca and translating it at Weill [Cornell Medical College], where doctors see patients with chromosomal abnormalities and fertility issues.”

The CRG will conduct four major research projects:

• Cohen will explore the role of a family of proteins that bind small RNAs during the production of germ cells.
• Andrew Grimson, assistant professor of molecular biology and genetics in the College of Arts and Sciences, will explore the timing and targets of small RNA actions during germ cell formation.
• Dr. Darius Paduch, associate professor of urology and reproductive medicine at Weill Cornell, will study the roles and expression of small RNAs in human male germ cells and how testicular small RNAs differ in men with different types of infertility.
• John Schimenti, professor of genetics at the College of Veterinary Medicine, will develop technologies to investigate the function and targets of virtually all conserved small RNAs that are expressed during sperm production.
• Weill urologist and CRG co-director Dr. Peter Schlegel will oversee the CRG’s Outreach Core, which will provide public bimonthly seminars on reproductive health, work with clinicians outside the CRG and Cornell who have questions about small RNA, and provide means for residents to train at the center to learn techniques for investigating small RNAs.
• Jen Grenier, director of Cornell’s new RNA Sequencing Core funded by the grant, will head the facility that will sequence the small RNAs. This full service will be made available to researchers campuswide.The CRG is funded by the National Institute of Child Health and Human Development’s Specialized Cooperative Centers Program in Reproduction and Infertility Research, a branch of the NIH.