3D yeast colony genomics: A model for cancer progression and development of drug resistance in biofilms
Summary of project results
Researchers of the YEASTSEQ consortium, comprising two teams from Prague and one from Oslo, have combined cutting edge scientific techniques with the simplicity of the yeast colony model system to investigate basic cellular differentiation and communication. The Czech teams previously demonstrated that yeast colonies behave as simple multicellular organisms in which cells differentiate, acquire specific properties and communicate with each other. Of particular interest was the finding that two major colonial cell subpopulations exhibit properties and interactions similar to those of solid tumour and of other cells in mammals. They also uncovered cell subpopulations with specific properties within colony biofilms of wild yeast strains, which contribute to the high environmental resistance of the entire colony population. By applying novel methodological approaches (next-generation sequencing provided by the Norwegian team), YEASTSEQ shed new light on molecular mechanisms involved in colony cell differentiation and development. RNA sequencing was used to examine gene expression, and highlighted metabolic and regulatory mechanisms involved in the differentiation of smooth colonies, in the formation of upper cells with properties analogous to cancer cells, and in the differentiation of surface and invasive cells forming colony biofilms. DNA analysis revealed mutations appearing in aggressively growing colony sectors escaping colony regulatory controls, and further research identified the genes responsible. Epigenetic analysis of chromatin structure added information on the control of gene expression, and in combination with the RNA data confirmed and expanded the network of regulatory and metabolic processes underlying cell differentiation. The results of the project were analysed and will be presented mainly in the form of original scientific publications (submitted or prepared for submission). These publications include new methods of differentiated cell separation, and those enabling analysis of lower cell numbers than ever before in yeast. The results reveal fundamental traits of tumor-like yeast cells and should guide further studies of medically important pathogenic yeast biofilms.
Development of experimental methodologies e.g. FAIRE and CHIP has benefited both sides, new skills related to next generation sequencing, e.g. library preparation and bioinformatics training has benefited Czech groups and branching out into a new area of research, involving microorganisms has expanded the expertise of the Oslo group. New data acquired during the project significantly increased knowledge in the field of study and has been/will be disseminated to scientific community in the form of presentations and publications. Students have been able to gain experience and publish research and to collaborate with experts in other fields. The project brought new job opportunities in Czech groups. Both Czech groups are world leaders in yeast colony biology, with emphasis on structure development and cell differentiation. They used their biological knowledge, methodological background and instrumentation to drive fulfillment of the project aims. The Norwegian team contributed cutting-edge DNA and RNA sequencing research technology and data analysis, opening new dimensions to yeast colony research. The Czech partners performed all yeast work (e.g., culture, DNA/RNA extraction, cell fractionation, microscopy, etc.), whilst the Norwegian partner performed DNA/RNA sequencing and oversaw data analysis. New methods of cell separation and low-input epigenetic analysis were developed under the partnership, and 5 junior scientists were trained in next-generation sequencing and data processing in Oslo and 4 in FAIRE/Chip sample preparation during the Norwegian partners stay in Prague. The Czech and Norwegian groups will continue to work together to complete and fully exploit the work begun by this collaboration. Additional ChiP experiments above the scope of current project have been already initiated. The project performed basic research, with no immediate societal economic impact, but which is expected will lead to innovations in cancer and resistant biofilm research. New knowledge was disseminated at scientific meetings and in the submitted and in-preparation publications. Immediate socio-economic benefits included positions for new researchers, PhD students and administrative staff covered by the project. A well gender-balanced international team (2 PIs were female) was involved, including one female returning from maternity leave.
The information on this page has been provided by the programme operator.