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Partner 1A - Karolinska Institutet, Department of Biosciences and Nutrition

Contact persons

	Link to Jan-Åke Gustafsson's CV.

University and research group information

Karolinska Institutet (KI), founded in 1810, is Sweden’s only university to focus exclusively on the field of medicine. Situated in Stockholm, it is Sweden’s largest medical research centre, and accounts for roughly 45% of the country’s university based medical research. It is also home to the country’s largest medical school. 2500 postgraduate students and 2800 research staff (57% women) work in over 600 research units of KI.

KI is responsible for awarding the annual Nobel Prize in Medicine or Physiology. Research at KI has a strong European dimension, with around 400 contracts within EU Framework Programmes. Of these contracts, about 100 are or have been coordinated from KI.

The Department of Biosciences and Nutrition is a department within the Karolinska Institutet. The department houses three units; Center for Biotechnology (CBT), Center for Nutrition and Toxicology (CNT) and Center for Structural Biochemistry (CSB). The department is located at the NOVUM Research Park in Huddinge, 15 km south of Stockholm.

The main areas of research are molecular biology, molecular immunology and receptor biology at CBT, nutrition and genotoxicity of environmental pollutants at CNT, and structural biochemistry using X-ray crystallography, electron microscopy, nuclear magnetic resonance spectroscopy (NMR) and molecular dynamic simulations at CSB.

The research groups led by Prof Jan-Åke Gustafsson and Dr Ingemar Pongratz are participants in CASCADE.

Contribution to CASCADE

Nuclear receptors constitute one of the most abundant classes of transcriptional regulators, and are involved in processes as diverse as metabolic regulation, sexual differentiation and embryonic development. To date approximately 70 mammalian nuclear receptors have been identified. For 28 of these, activators or ligands have also been identified.

We are interested in different aspects of estrogen signalling, mainly focusing on different aspects of ERbeta function. This work includes molecular mechanistic studies, physiological aspects of ER function and gene expression profiling of estrogen regulated genes. The ultimate goal or this project is to use this knowledge to improve our understanding of human disease and for improved diagnosis and therapy.

The bHLH-PAS Protein Family
Early studies identified the aryl hydrocarbon receptor (AhR) as a mediator of the toxic effects of polycyclic and halogenated aromatic hydrocarbons including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Further investigation has led to the description of a complex signal transduction pathway involving heterodimerization with the Ah receptor nuclear translocator protein (ARNT) to form a transcriptionally active dimer that binds xenobiotic response elements in the upstream promoter/enhancer region of target genes. We are currently carefully dissecting the interplay between the AhR/ARNT complex and selected NR (ERa, ERb, LXRa).

Representative scientific articles as relevant to CASCADE