Dr Mikael Bjorklund
Growth regulation in multicellular organisms
Cell growth occurs as cells increase their biomass and/or divide. How growth and proliferation are coupled is an important question in biology with significant implications in cancer. Although cell cycle progression is extensively studied , the mechanisms of cell growth (=increase in cell size) particularly in multicellular organisms are very incompletely understood. The aim of my laboratory is to utilize genome-scale approaches to understand growth regulation at the cellular level. Yeast has been the classical model to study cell size, but it is unclear how well these processes are concerved. For this reason, we use Drosophila and mammalian cells as our primary models. Previous work has identified several hundred genes in Drosophila cells whose loss-of-function results in changes in cell growth and cell cycle (Björklund et al, Nature 2006). Although it is generally thought that treatments that cause cell cycle arrest result in increase in cell size, the interesting observation from our study was that cell cycle and cell size increase are not necessarily coupled in this way. This has been more recently confirmed in yeast by others.
Drosophila ORFeome resource
Drosophila has been an instrumental model organism for the analysis of cell growth. To expand the genetic toolbox of Drosophila researchers, our laboratory is working in collaboration with prof. Basler's laboratory in Zurich to establish a genome-scale resource of transgenic UAS-ORF Drosophila strains. These can be used for systematic phenotypic screens by overexpression to complement existing loss-of-function approaches in Drosophila. Using cell based and in vivo overexpression screens we identified novel kinases regulating Wnt/wg pathway activity (Schertel et al, Dev. Cell 2013). Expression of ORFs thus appears as a promising approach to uncover phenotypes, which have been missed in RNA interference and other loss-of-function screens.
Miettinen, T. P. and Bjorklund, M. (2015). "Mevalonate Pathway Regulates Cell Size Homeostasis and Proteostasis through Autophagy." Cell Rep. 13.
Miettinen, T. P. and Bjorklund, M. (2015). "Modified ribosome profiling reveals high abundance of ribosome protected mRNA fragments derived from 3' untranslated regions." Nucleic Acids Res 43(2): 1019-1034.
Miettinen, T. P. and Bjorklund, M. (2014). "NQO2 is a reactive oxygen species generating off-target for acetaminophen." Mol Pharm 11(12): 4395-4404.
Miettinen, T. P., Pessa, H. K., Bjorklund, M. et al. (2014). "Identification of transcriptional and metabolic programs related to mammalian cell size." Curr Biol 24(6): 598-608.
Bischof, J., Sheils, E. M., Bjorklund, M., et al. (2014). "Generation of a transgenic ORFeome library in Drosophila." Nat Protoc 9(7): 1607-1620.
Schertel, C., Huang, D., Bjorklund, M., et al. (2013). "Systematic screening of a Drosophila ORF library in vivo uncovers Wnt/Wg pathway components." Dev Cell 25(2): 207-219.
Bonke, M., Turunen, M., Bjorklund, M., et al. (2013). "Transcriptional networks controlling the cell cycle." G3 (Bethesda) 3(1): 75-90.
Bischof, J., Bjorklund, M., et al. (2013). "A versatile platform for creating a comprehensive UAS-ORFeome library in Drosophila." Development 140(11): 2434-2442.
Alhopuro, P., Bjorklund, M., et al. (2010). "Mutations in the circadian gene CLOCK in colorectal cancer." Mol Cancer Res 8(7): 952-960.
Tuupanen, S., Turunen, M., Bjorklund, M. et al. (2009). "The common colorectal cancer predisposition SNP rs6983267 at chromosome 8q24 confers potential to enhanced Wnt signaling." Nat Genet 41(8): 885-890.