Taufika Williams

The vision of the Center for Human Health and the Environment (CHHE) is to become a global leader in environmental health sciences (EHS) along the continuum from genes to populations by building on NC State’s unique research strengths and resources in quantitative biology, -omics and analytical technologies, and diverse model organisms, as well as its emerging strength in human population science. Through the purposeful interfacing of different disciplines and a systems biology framework integrating all levels of biological organization - biomolecule, pathway, cell, tissue, organ, model organism, human, and human population - CHHE will elucidate fundamental mechanisms through which environmental stressors interface with pathways, the genome, and epigenome to influence human health outcomes. CHHE has made outstanding progress in the first funding cycle. CHHE has significantly: (1) advanced innovative multi-disciplinary EHS team research; (2) expanded its NIEHS grant base; (3) increased EHS capacity at its partner institutions, East Carolina University and North Carolina Central University; (4) cultivated the next generation of EHS leaders; and (5) developed multi-directional engagement with communities affected by exposure to toxic metals and per- and polyfluoroalkyl substances. During our first funding cycle, four Research Interest Groups (RIGs) evolved organically and the Emerging Contaminants, Environmental Epigenetics and Genetics, Pulmonary Health, and Behavior and Neuroscience RIGs now represent CHHE thematic areas. In the coming cycle, we have enhanced our three facility cores to increase the impact and the basic science and translational capacity of our membership. The Systems Technologies Core provides cutting-edge technologies involving genomics, metabolomics, metallomics, and proteomics. The Comparative Pathology Core provides pathologic phenotypic assessment of the many model organisms used by members and imaging support with links back to omics technologies. The Integrative Health Science Facility Core facilitates bidirectional translation between basic science and public health outcomes by providing data science analysis and visualization support for analysis of human population and multi-omic studies as well as population-based study expertise. As a land-grant university, NC State has a dedicated community engagement philosophy that augments CHHE’s Community Engagement Core and fosters relationships between CHHE and affected communities in NC which leads to collaborative interaction among researchers, educators, and citizens to enhance EHS knowledge, literacy, and health. A strong Career Development Program for early- and mid-career investigators is coordinated with a robust Pilot Project Program that supports collaborative and multidisciplinary EHS projects to enhance the research success of our members. Our CHHE mission is to continue to evolve as a premier NIEHS EHS Core Center and serve as the nexus of EHS research at NC State by providing focus, resources, and leadership for interdisciplinary research that will improve human health locally, nationally, and globally.

Behavior supports the stage on which the interplay between the environment and the genome guides evolution. Behavioral adaptations to environmental cues determine survival and reproductive success. Among those environmental cues none are more important than chemical signals. Indeed, odor-guided behavior is essential for most organisms for food localization, avoidance of environmental toxins or predators, oviposition site selection, kin recognition, species recognition and mate selection, and reproduction. The long-term objective of this research program is to obtain a complete description of the genetic architecture that shapes odor-guided behavior in Drosophila melanogaster. This requires identification of all the genes that contribute to olfactory behavior, characterization of genetic interactions among them, and identification of polymorphisms that generate phenotypic variation in nature. The avoidance response to a repellent odorant, benzaldehyde, serves as a simple and convenient model for odor-guided behavior. Elimination of genetic variance by using controlled genetic backgrounds together with a rapid and quantitative behavioral assay that enables accumulation of large data sets through repeated measurements provides enough statistical power to reproducibly resolve not only large phenotypic effects, but also small smell impairments. The previous funding period achieved characterization of several previously identified smell-impaired (smi) genes at the molecular level. Extended screens identified an additional 79 candidate smi genes. Furthermore, recombination mapping, using a population of recombinant inbred lines, resulted in the discovery of a new highly polymorphic gene, Vanaso, that contributes to sex-specific phenotypic variation in olfactory behavior. The experiments proposed in this application build on the foundation established during the previous funding period. The specific aims of this proposal are: 1- To characterize a set of new smi genes in greater molecular detail; 2A - To identify gene products that are up-regulated or down-regulated in co-isogenic smi lines of Drosophila melanogaster as a consequence of P-element insertions at smi loci through the use of high density oligonucleotide microarrays; 2B - To quantitatively assess the contributions to odor-guided behavior of new candidate smi genes identified in Specific Aim 2A; 3 - To organize smi genes in epistatic networks; and, 4 -To perform association studies to identify polymorphisms in Vanaso and three odorant receptor genes that may contribute to phenotypic variation in olfactory avoidance response to benzaldehyde in natural populations. The completion of these specific aims will lead to a greater, more comprehensive understanding of the genetic architecture of olfactory behavior.

This is an amended application of a previously submitted proposal for a Fogarty International Research Collaboration Award to extend the parent grant RO1GM59469-08 Molecular genetics of olfaction in Drosophila (4/1/03-3/31/08).