3D yeast colony genomics: A model for cancer progression and development of drug resistance in biofilms

 

Project summary

Studies of cell differentiation, spatial position, cell-cell interaction and signaling within organized yeast communities such as colonies and biofilms have revealed the existence of unique processes associated with the yeast multicellular life-style. These findings showed that specific attributes (such as cell differentiation and specialization) attributed previously only to metazoans have their counterparts in yeast multicellular structures. Yeast colonies therefore recently became an excellent simple model (with a broad spectrum of different manipulation techniques available) for investigation of these processes, the molecular principles of which are often conserved among eukaryotes, including humans.

Recent findings of both Czech teams behind this proposal showed that colonies behave as simple multicellular organisms in which cells differentiate, acquire specific properties and communicate with each other. The main aim of the project is to identify, using next-generation DNA/RNA sequencing methodology provided by the Norwegian partner, novel molecular mechanisms involved in development of yeast cells within differentiated colony resembling cells of mammalian solid tumors, as well as those involved in development of protective mechanisms in yeast biofilm colonies.

The research is based on recent findings of both Czech partners regarding metabolic parallels between differentiated yeast colonies and tumor-affected organism and of those regarding differentiation and defense strategies in biofilm colonies.YEASTSEQ project could provide new insight into tumor cell physiology and it will contribute to the elucidation of specific properties of biofilms, their enormous resistance and their adaptability to various environmental niches, which make it difficult to combat clinical, industrial and environmental biofilms.

Discoveries in this area can also help identify molecular mechanisms involved in the interaction of pathogenic yeasts with human tissues and in the future may help to improve the prevention and treatment of mycoses in immunocompromised patients. YEASTSEQ will also create new long-term cooperation between Czech and Norwegian teams and significantly expand the knowledge and skills of the participating teams, including their PhD students and young researchers.

Specific aims include:

1. Quantitative analysis of transcriptomes of different types of differentiated cells of yeast colonies by RNA Seq;
2. Identification of the mutation rate in the major cell subpopulations within the colony by whole genome re-sequencing
3. Determining of epigenetic regulations, potentially involved in the reprogramming of structured biofilm colonies by FAIRE and Chromatin Immunoprecipitation (ChIP).