Research in Gene Regulatory Networks

Background

Several ORNL and collaborative projects are developing computational and experimental methods to identify Gene Regulatory Networks (GRNs), the integrations of genes, regulatory DNA elements, and transcription factor proteins that control the activity of cellular and biochemical pathways.

Gene expression and levels of the resulting protein products are tightly controlled by complex interactions between transcriptional regulation, translational control, and mRNA and protein stability. Furthermore, even within a single organism, the interplay between regulatory mechanisms for a given gene varies according to cell type, cellular environment, and the cell's current physiological and nutritional status. Gene networks are thus important in transducing genetic signals into phenotypic variation and integrating genomic information, environmental cues, and physiological or developmental stimuli.

Changes in these networks over both evolutionary and developmental time scales are critical to the formation of phenotypic complexity, diversity, and variability. Collectively, GRNs underlie the complex and intricate nature of biological systems and allow and organism to survive in a constantly changing milieu. Understanding the architecture of GRNs will fundamentally advance the study of core biological problems.

Projects

The current research projects include the following:

• Elucidating Gene Regulatory Networks in the Metazoa:
  A ORNL Collaboration initiated by an ORNL LDRD project.
  • Brynn Jones et al.
    • Experimental, microarray-based identification of genes important in mouse hair and skin biology.
  • Jay Snoddy, Stefan Kirov, Bing Zhang, et al.
    • Integrative and Comparative Data Mining for inferencing cis-Regulatory Elements (CRE) and trans-regulatory interactions.
  • Michael Leuze, (Computational Science and Mathematics Division) et al.
  • Computational Methods to infer CRE motifs


• Genome/Proteome Analysis and Gene Regulatory Networks in Microbials
  • Frank Larimer et al;
  • Other members of the Genome Analysis and Systems Modeling Group; and,
  • Other Collaborators, esp. in the DOE Genomes To Life Project ;
    • GTL Goal 2: Gene Regulatory Networks
    • ORNL/PNL project: Genomes to Life Center for Molecular and Cellular Systems


• Metazoan Phenotype and Uncovering the Underlying Genes and Gene Regulatory Networks
  • Involves several multi-institutional collaborations
  • Jay Snoddy, Bing Zhang, Stefan Kirov, Rob Williams (UTHSC), Dan Goldowitz (UTHSC), Kathleen Grant (Wake Forest), et al.
  • Part of the NIH-funded, Comparative and Collaborative Analysis of Metazoan Phenotype Project (ccbioinfo.org)
  • Part of bioinformatics research, development, and support with other large collaborative projects (e.g. Tennessee Mouse Genome Consortium and the Innovative Neuroscience Initiative on Alcoholism (Iniastress.org project).
  • This especially uses mouse genetics (e.g. Quantitative Trait Linkage Analysis of mouse transcriptosome data or the creation of new mutant mouse models) to also begin to get access to the molecular nature of the genes and gene networks that create specific phenotypes.

A Few Other Links of Interest

• UT-ORNL Graduate School of Genome Science and Technology
• Comparative and Collaborative Analysis for Metazoan Phenotype
• Tennessee Mouse Genome Consortium
• Innovative Neuroscience Initiative for Alcoholism
  

• Oak Ridge National Laboratory
  • Life Sciences Division
    • Genome Analysis and Systems Modeling Group
    • Computational Biology Program
    • Mammalian Genetics Program
  • Computer Science & Mathematics Division
    
• University of Tennessee
  • Division of Biology
    • Ecology and Evolutionary Biology Department
    • Biochemistry, Cellular, and Molecular Biology Department
  • Computer Science Department
  • Center for Genomics and Bioinformatics
    
• Joint Institute of Biological Sciences
• Joint Institute of Computational Science
  
• Department of Energy
  • Office of Science
    • Biological and Environmental Research
    • Advanced Scientific Computing Research
  • Genomes to Life Program
    
• National Institutes of Health
  • National Institute on Drug Abuse
  • National Institute of Mental Health
  • National Institute on Alcohol Abuse and Alcoholism
  • National Human Genome Research Institute
  • All NIH Institutes

(If you know of other relevant ORNL or collaborative projects with either major ORNL or UT-ORNL components, please forward to Jay Snoddy and Betty Lou Alspaugh, who maintain this page).