“The medaka Kiyosu panel: dissecting GxE effects of environmental chemicals”
In this proposal we have assembled an international, multi-disciplinary team to exploit a unique resource, the wild-derived inbred Kiyosu panel of medaka (Japanese rice-paddy) fish to investigate how environmental exposures have a variable impact on individuals through genetic variation Here we investigate “Gene x Environment” (GxE) effects to both quantify phenotypic changes and importantly gain mechanistic, molecular understanding of the biological pathways involved in contaminant responses in cardiovascular and skeletal toxicity.
Ewan Birney, European Molecular Biology Laboratory
Jochen Wittbrodt, University of Heidelberg
Jared Goldstone, Woods Hole Oceanographic Institution
Welcome to the Kullman Lab home page:
Environmental chemicals are increasingly implicated in the etiology of many chronic diseases. In the Kullman laboratory we use molecular, comparative and functional genomic approaches to examine how exposure to environmental stressors (dys)regulate complex interactions between genotype and phenotype. Our laboratory is particularly interested in neural and endocrine pathways that govern critical steps of embryonic development. Much of our work is focused on nuclear receptors and ligand activated transcription factor signaling. These receptors facilitate the cellular response to endogenous and exogenous ligands by coordinating complex transcriptional responses. Nuclear receptors have well-defined roles during vertebrate development and it is recognized that activation and or inhibition of receptor signaling may have profound organizational effects that manifest either during embryogenesis or remain latent until juvenile development and/or adulthood (i.e. developmental basis of adult disease). The overarching goal of the lab is to establish a mechanistic understanding of the relationship between chemical-receptor interactions and resultant pleotropic and epigenetic effects influencing both human and environmental health.
The Kullman laboratory employs a combination of in vitro (human, mouse, fish cells lines) and in vivo (small aquarium fish) models for mechanistic discovery and phenotypic determination. For in vivo studies we utilize small aquarium fish models of disease including both zebrafish (Danio rerio), and medaka (Oryzias latipes). These animals are increasingly used as vertebrate model systems for both human and environmental health. There are may benefits to these models including their suitability for forward and reverse genetic manipulation, ease of handling, transparent nature of embryos, and genetic tractability. Driving research with these comparative models is the general assumption that there are evolutionarily conserved regulatory processes associated with observed toxicities and pathologies. Discovery of conserved sets of biological responses will focuses our attention on genes and pathways that have greater biological relevance to disease etiology and pathology.