Research interests
Genome sequencing projects and gene association studies identify new genes that may have important disease associations. To understand the function of the identified genes in in vivo context requires valid model organisms. Based on remarkable conservation in cell physiology during evolution it is possible to use genetically tractable model organisms such as the fruit fly (Drosophila melanogaster) and zebrafish (Danio rerio) in studies of genetic diseases, and also complex diseases like cancer, cardiovascular diseases or diabetes.
Our research group uses fruit flies and zebrafish – in order to identify key genes and proteins involved in the immune response. Flies have a highly sophisticated immune defense. In contrast to mammals, Drosophila has no adaptive i.e. antibody-mediated immunity, which makes it a valid model for studying the pattern recognition receptors and signaling pathways of the innate immunity. On this premise we use Drosophila as a model to discover novel classes of gene products that are important to combat pathogens. We have developed an RNA interference (RNAi) based in vitro screening method in Drosophila S2 cells (Rämet et al. (2002) Nature) which can be used in genome-wide scale to study functional significance of gene products for numerous cell based functions. During the past years, we have used this collection to identify new proteins necessary for: 1. recognition and phagocytsosis of bacteria (Rämet et al., 2002 Nature; Kocks et al., 2005 Cell; Ulvila et al., 2011 J Leuk Biol); 2. RNAi phenomenon itself (Ulvila et al., 2006 J Biol Chem), 3. NF-kB signaling (Kleino et al., 2005 EMBO J; Kleino et al., 2008 J Immunol; Valanne et al., 2010 J Immunol) and 4. JAK/STAT signaling (Kallio et al., 2010 FASEB J). Currently, we are further characterizing selected genes identified from these screens.
Besides the Drosophila model, we have established a state-of-the-art zebrafish facility in order to carry out large-scale transposon-based screens in zebrafish to identify gene products that are necessary for normal resistance against selected pathogens. This system enables forward genetic screening with a model organism with fully developed immune system. For example, we will use a zebrafish model for tuberculosis to identify new disease-modifying genes.
Main Research Objectives:
1. To identify and molecularly characterize new genes involved in the innate immune signaling (JAK/STAT and NF-kB), viral defense, phagocytosis and microbial recognition using genome-wide RNAi-based functional screens in cultured Drosophila cells.
2. To utilize modern Drosophila in vivo research tools to validate the in vitro observation from the genome-wide screen in vivo.
3. To carry out large-scale transposon-based mutagenesis based genetic screens in zebrafish to identify genes required for selected pathophysiological conditions.
Current sources of external funding:
Academy of Finland, Biocenter Finland, Medical Research Fund of Tampere University Hospital (EVO), Sigrid Juselius Foundation, Tampere Tuberculosis Foundation, Jane and Aatos Erkko Foundation
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Contacts
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Principal investigator:
Mika Rämet, MD, PhD
mika.ramet(at)uta.fi
tel. +358 50 433 6276
Post address:
BMT / Experimental Immunology
FI-33014 University of Tampere, Finland
Street address:
Arvo Ylpön katu 34
33520 Tampere
Finland
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