Transomics Research Core
Research Accomplishments - 2006
During 2006, the Transomics Research Core (TrRC) continued to expand its emphasis on combining and applying various “omic” technologies to environmental health research. This year a major achievement was achieved to bring the integration of various omic technologies in support of environmental health research to fruition.
The TrRC assembled a group of CEHS investigators (Threadgill, PI, Pomp, Zou) with a broader range of computational scientists from UNC’s Department of Computer Science and Department of Statistics and Operations Management to respond to the NIH Director’s Roadmap program for Interdisciplinary Research Consortia. The TrRC group submitted a pre-application that was competitively reviewed and was one of the few teams selected to submit a full proposal. This application, titled ‘Interdisciplinary Research Consortia on the Genetics and Co-Morbidity of Stress’, was assembled over the last six months and submitted in mid-Dec, 2006. It consisted of 13 components and included the parent administrative application, core, training and out-reach applications and nine research project applications. The major emphasis was deployment of systems genetics, a new interdisciplinary research field combining genetic segregation with the omic sciences, to investigate the inter-individual variation in response to metabolic and psychosocial stress, the combination of which is the most common disease-associated environmental exposure experienced by Americans in modern society. The TrRC group will develop and combine cutting-edge computational tools, data mining algorithms, and data visualization modules with a novel mouse population that models the heterogeneous human population to understand the causative relationships among DNA variation, endo-phenotypes and a variety of terminal diseases, including altered neurological function, immune function, obesity and metabolism and cardiovascular disease.
Two other applications are currently under review. TrRC members collaborated with members of the Obesity Susceptibility Research Core to submit an R01 application to investigate the role of the physical environment in modulating obesity using novel mouse models of polygenic obesity and exercise (Pomp, PI, Threadgill). The second application under review is a resubmitted application in response to a PA for Bioengineering Partnerships (Rusyn, PI, Threadgill, Wright). This application is a collaboration between members of the CEHS and members of the Center for Environmental Health Sciences at MIT (Griffith, Fry). The goal of this partnership, enabled by the TrRC, is to develop new approaches to incorporate genetic variation into classical toxicology testing paradigms. This will be achieved by developing novel liver bioreactors and a prioritization scheme for selecting specific mouse genetic backgrounds for toxicity testing.
Additional collaborative research activities over the previous year include:
Dr. Ibrahim developed methods to use Bayesian statistics on –omics data (Biometrics, in press). Through a collaboration with Threadgill, his group used these new approaches to simultaneously combine exposure, response and temporal variables to identify biomarkers strongly associated with environmental exposures of alkylation.
Dr. Wright, Zou, Threadgill, and Lauder (Developmental Research Core) developed a comparative approach to investigate inter-individual variation in gene expression across different brain regions associated with susceptibility to autism (Genetics, 2006). These investigators are now interrogating this data, in combination with a panel of behavioral analysis using mouse models to identify causal links to autistic characteristics. Similarly, Rusyn and Threadgill developed a database of gene expression variation among livers in different mice (Hepatology, in press). The investigators are now expanding this approach to understand how gene expression changes differentially in response to hepatotoxicants.
Dr. Watkins reported that some patients receiving the maximum recommended daily dose of acetaminophen develop elevated serum biomarkers indicative of liver toxicity (JAMA, 2006). Using support provided by the TrRC, Watkins, Rusyn, and Threadgill developed a platform using mouse models to identify the genes underlying susceptibility to liver damage. This collaborative work has lead to a manuscript currently under review at Science that reports the use of a new mouse model of the human population to identify genetic causes of toxicity and a method to identify exposures with potential toxicity in a subset of individuals. The TrRC is supporting the adoption of the new population model to investigate a wide range of exposures.
