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UC-Riverside Researchers Receive $1.5M NIH Grant for Research into Nuclear Receptors

NEW YORK (GenomeWeb News) – Researchers at the University of California, Riverside have received a four-year, $1.5 million grant from the National Institutes of Health to study the effect of single nucleotide polymorphisms on a special class of proteins that regulate the expression of genes in response to hormones, vitamins, and drugs.

The award from the National Institute of Diabetes and Digestive and Kidney Diseases will be used by the researchers to study how SNPs affect proteins called nuclear receptors, which are transcription factors that regulate the expression of genes involved in virtually every aspect of human physiology and diseases, UC-Riverside said.

While some SNPs are associated with structural and functional changes in proteins that are encoded by genes, most are outside of the protein-coding portion of the gene and found in the regulatory regions of genes, said Frances Sladek, a professor of cell biology and toxicologist at UCR and the principal investigator on the grant.

"We will characterize both types of SNPs to help predict disease susceptibility and response to drug treatments," she said in a statement. "Such a characterization will help lay the foundation for personalized medicine, ultimately leading to more effective and hence less costly health care costs."

According to the grant's abstract, Sladek and her colleagues will employ biochemical, molecular, genomic, and bioinformatic approaches to three specific aims. Those aims are the determination of DNA binding specificity of a select group of nuclear receptors using an integrated approach based on protein binding microarrays; expanding protein binding microarrays to 1 million reactions in order to identify affinity-altering SNPs for nuclear receptors in regulatory regions of genes that are associated with disease and drug metabolism; and using protein binding microarrays to investigate factors on nuclear receptor-DNA binding including different ligands, nuclear receptor partners, and co-regulatory molecules.

Results from the research will be made publicly available on a UC-Riverside website dedicated to the project and other public databases, the university said. Sladek and her team also will develop web-based tools for motif finding and target gene prediction.