UCLA professors of microbiology, immunology and molecular genetics Alexander Hoffmann and Douglas Black have been awarded a three-year, $6 million grant from the National Institutes of Health’s Genomics of Gene Regulation (GGR) program of the National Human Genome Research Institute (NHGRI). Hoffman, director of UCLA’s new Institute for Quantitative and Computational Biosciences (QC Bio), conducts research to understand and decode the language of the cell. Black, a Howard Hughes Medical Institute Investigator, studies the regulation of alternative splicing in mammalian cells and the biochemical mechanisms that control changes in splice sites.
The grant will fund a new UCLA Center for the Ribonomics of Gene Regulation, and research on the immune system’s response to pathogens. The reseachers will examine how a type of white blood cell called a macrophage reacts to a bacterial pathogen, which can result in the activation of more than 1,000 genes. This model system will allow the scientists to examine various steps in the gene expression pathway to try to better understand control mechanisms.
The new center, part of QC Bio, will use state-of the-science genetic sequencing and computational modeling approaches to understand gene control of the immune response to pathogens. The scientists will analyze the expression of genes involves in a sequence of enzymatic events. They will study the role of gene structure and sequence, and the role of chromatin modifications and of trans-acting splicing factors in determining the identity of mature mRNAs and their associated synthesis rates, before adding the stimulus-responsive regulatory networks that confer mRNA half-life control and determine the abundance of each mRNA isoform.
Other participating UCLA faculty are Yi Xing, associate professor of microbiology, immunology and molecular genetics, and director of UCLA’s bioinformatics graduate program; Xinshu (Grace) Xiao, associate professor of integrative biology and physiology; Tracy Johnson, associate professor of molecular, cell and developmental biology and a Howard Hughes Medical Institute Professor; Jason Ernst, assistant professor of biological chemistry; Stephen Smale, professor of microbiology, immunology and molecular genetics; Sri Kosuri, assistant professor of chemistry and biochemistry; and Matteo Pellegrini, professor of molecular, cell and developmental biology and co-director of QC bio.
“There is a growing realization that the ways genes are regulated to work together can be important for understanding disease,” said Mike Pazin, a program director in the functional analysis program in NHGRI’s Division of Genome Sciences. “The GGR program aims to develop new ways for understanding how the genes and switches in the genome fit together as networks. Such knowledge is important for defining the role of genomic differences in human health and disease.”