In this study, I sought to identify genes regulating the global molecular program for development of sessile multicellular communities, also known as biofilm, of the eukaryotic microorganism, Saccharomyces cerevisiae (yeast). Yeast biofilm has a clinical interest, as biofilms can cause chronic infections in humans. Biofilm is also interesting from an evolutionary standpoint, as an example of primitive multicellularity. By using a genome-wide screen of yeast deletion mutants, I show that 71 genes are essential for biofilm formation. Two-thirds of these genes are required for transcription of FLO11, but only a small subset is previously described as regulators of FLO11. These results reveal that the regulation of biofilm formation and FLO11 is even more complex than what has previously been described. I find that the molecular program for biofilm formation shares many essential components with two other FLO11-dependent phenotypes: mat formation and invasive growth. Based on these findings, I suggest that there is a common genetic program for phenotypes governing cellular differentiation. Furthermore it is found that the epigenetic switching between Flo11+ and Flo11- phenotypes is required for cooperativity and mat formation. In addition, through the study of FLO11 regulation, strong evidence was found of a novel regulatory mechanism of the evolutionary conserved protein kinase A (PKA) pathway, where one of the PKA catalytic subunits are responsible for both repression of transcription and activation of translation of FLO11. In conclusion, I have conducted the first global study of the genetic program for yeast biofilm formation on polystyrene. This work provide several target genes as good basis for further research of biofilm, that I believe can contribute to fields such as cell biology, genetics, system biology and medical science.
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Department of Biology, Faculty of Science, University of Copenhagen, 2014