BBB seminar: Rune Blomhoff
Molecular imaging as a tool for studying dietary regulation of gene expression
Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo
The human diet contains several thousand different molecules, many of these with quite potent biological activity. A number of dietary compounds have significant direct or indirect effects on signal transduction and gene expression. The specific physiological effects are not easy to predict from in vitro studies using cell cultures and cell-free model systems. Since the cellular environment is of crucial importance for regulation of gene expression, we have developed a novel in vivo model which enables real-time imaging of gene expression in living mice. Application of genomic tools to study the integrated effects of nutrients on gene regulation holds great promise in increasing the understanding of how nutrients affect molecular events, and eventually health and disease in an intact organism.
Previous studies had demonstrated that it was possible to image luciferase labelled bacteria inoculated in mice in vivo. This suggested to us that it would also be possible to detect light from internal organs of luciferase transgenic mice. We therefore developed transgenic mice using the reporter luciferase controlled by small response elements or complete promoters. Following injection of the substrate, luciferin, light can be detected externally from these transgenic animals by sensitive CCD video cameras.
In such models, we have shown that the strength of the light reflects gene expression or transactivation of the specific response element that controls the luciferase. In a large panel of transgenic reporter mice we are now elucidating the role of nutrients, pharmacological drugs or other environmental factors in regulation of disease-related genes in vivo. The transgenic reporter mice include luciferase controlled by NF-kB response elements, electrophilic response elements, retinoic acid response elements, γ GCS promoter, heme oxygenase type 1 promoter, superoxide dismutase type 1 promoter and interleukin-2 promoter, as well as a protein kinase A sensitive luciferase reporter where the luciferase activity is tuned off in the presence of PKA activators.
Host: Marit Bakke, Department of Biomedicine
A major scientific interest of Professor Rune Blomhoff is to unravel the effects of dietary compounds on signal transduction and gene regulation. As a tool to investigate changes in gene transcription in an in vivo setting, Blomhoff has, as one of the pioneers in the field, developed transgenic mouse models that enable real-time imaging of gene expression in living animals. In addition to having developed molecular imaging in transgenic mice, Rune Blomhoff is internationally recognised for his considerable contributions to our present understanding of the absorption, transport, storage and function of vitamin A (retinoids). He has published about 150 research papers and received numerous awards for his scientific work and innovations.