Regulation of iron homeostasis in cyanobacteria
PTDC/BIA-MIC/101036/2008


Summary

Cyanobacteria form a highly versatile group of microorganisms which have successfully adapted to various environmental conditions on Earth. Their living habitats range from soil and freshwater to the open sea; and they contribute to a significant proportion of the global biomass production. Besides their ecological importance, their capacity for adaptation has made the discovery of the underlying mechanims a fascinating field of research. Cyanobacteria have to respond to many environmental cues, integrating various external and internal stimuli to select the 'proper response'. To better understand how this is achieved, models of the underlying molecular networks need to be constructed, analysed and visualized (Springer, 2014). Moreover, the complex behaviour of cells cannot be studied using a single method, but has necessarily to be elucidated by systems-based approaches including methods of in vivo, in vitro and in silico biology. Such an approach was undertaken in our project.

As model systems, we used Synechocystis PCC6803. Although this model cyanobacterium has been intensively studied, little is known about the functioning of its molecular regulatory networks on a system-wide level. By an integrated computational and experimental approach, we reconstructed in silico and validate in vivo the regulatory network involved in iron homeostasis in Synechocystis PCC6803. These efforts were assisted by detailed functional studies. The regulation of iron homeostasis is a highly interesting process to study, as iron is an essential mineral and plays a key role in numerous cellular mechanisms, but it is both difficult to access and toxic in high concentrations. Thus, many organisms have involved regulatory systems to keep iron within a narrow concentration range. This is especially the case in cyanobacteria, for which iron is an indispensable cofactor in oxygenic photosynthesis and frequently the limiting factor for growth.

To establish a basis for our investigations, we constructed CyanoEXpress, a database integrating standardized genome-level expression data from public repositories for Synechocystis sp PCC6803. At present, CyanoExpress provides direct access to the largest collection of gene expression data set for Synechocystis (Bioinformation, 2012). Besides providing the basis for our computational analysis, CyanoExpress is also a important resource for the research community. It enables users the visualization and exploration of Synechocystis transcriptional response to different environmental or genetic perturbations. We also used the data collected in CyanoEXpress to carry out a comprehensive meta-analysis of Synechocystis expression data, which enabled us to derive detailed network models of coordinated adaptation to environmental stress (Scientific Reports, 2016).

Furthermore, we profiled the Synechocystis' transcriptional response to iron depletion using microarray that contain both probes for protein-coding and non-coding transcripts (G3, 2012). Many of the differentially regulated were associated with iron transport, photosynthesis, or ATP synthesis. Comparing with previous studies, we identified a core set of genes involved in iron stress response. Interestingly, these core response genes included components that are important for assimilation of inorganic carbon, suggesting a link between the carbon and iron regulatory networks. Beyond protein coding genes, we could identify differentially regulated small RNAs and antisense RNAs as potential novel components of the iron regulatory network in Synechocystis, and thus unrevealed a novel layer of complexity of iron homeostasis in cyanobacteria.

Project Team




Databases & Software

CyanoExpress

CyanoEXpress is a web database for interactive exploration and visualisation of transcriptional response patterns in Synechocystis sp. PCC6803. It comprises expression data from more than 700 transcriptome measurements carried out in more than 30 independent studies. Notably, changes in expression during both environmental and genetic perturbations are included in the integrated data set.


Publications

Miguel HernŠndez-Prieto , Trudi Semeniuk , Joaquin Giner-Lamia and Matthias Futschik (2016) The Transcriptional Landscape of the Photosynthetic Model Cyanobacterium Synechocystis sp. PCC6803, Scientific Reports 6:22168 (pdf + html)

Miguel Hernandez-Prieto, Ravi Kalathur and Matthias E. Futschik (2014) Molecular networks, their analysis and representation, Chapter 24, 399-418, Springer Handbook of Bio- and Neuroinformatics, ed. Nik Kasabov, Springer (preprint-pdf, Book's web-page)

Miguel A. HernŠndez-Prieto, Verena SchŲn, Jens Georg, LuŪsa Barreira, Jo„o Varela, Wolfgang R. Hess and Matthias E. Futschik (2012) Iron deprivation in Synechocystis: Inference of pathways, non-coding RNAs and regulatory elements from comprehensive expression profiling, G3: Genes, Genomes, Genetics , 2 (12), 1475-1495 (html , pdf) (GEO-Data)

Miguel Hernandez-Prieto and Matthias E. Futschik (2012) CyanoEXpress: a web database for interactive exploration and visualisation of the integrated transcriptome of cyanobacterium Synechocystis sp. PCC6803, Bioinformation 8 (13) ,634-638 (Abstract, Pdf)


Presentations

Miguel A. HernŠndez-Prieto and Matthias E. Futschik (2013) Combined analysis under iron limiting conditions of microarray and RNA-seq data reveals novel transcriptional units and facilitates the prediction of a Fur-box in Synechocystis, ESF-EMBO Symposium, Pultusk, Poland

Matthias E. Futschik (2013) How the internal world of Synechocystis adapts to the ever-changing world outside: A comprehensive meta-analysis of its transcriptional responses, ESF-EMBO Symposium, Pultusk, Poland

Miguel A. HernŠndez-Prieto and Matthias E. Futschik (2012) CyanoExpress: A Comprehensive Database for Evaluating the Transcriptional Response in Synechocystis, ISPP 2012, Porto, Portugal (Pdf)

Miguel A. HernŠndez-Prieto , Verena SchŲn, Claudia Steglich , Wolfgang Hess and Matthias E. Futschik (2012) Simultaneous profiling of coding and non-coding RNAs from Synechocystis under iron-limiting conditions, ISPP 2012, Porto, Portugal

Miguel A. HernŠndez-Prietoa, Luisa Barreira, Claudia Steglich, Jo„o Varelab, Wolfgang Hess & Matthias E. Futschik (2011) Concerted responses to iron availability in cyanobacteria, 8th European Workshop on Molecular Biology of Cyanobacteria, Naantali, Finland (Abstract)

Matthias E. Futschik and Miguel A. HernŠndez-Prietoa (2011) The Transcriptional Landscape of the Cyanobacterium Synechocystis, 8th European Workshop on Molecular Biology of Cyanobacteria, Naantali, Finland (Abstract)

Miguel A. HernŠndez-Prietoa, Luisa Barreirab, Jo„o Varelab & Matthias E. Futschik (2010) Concerted responses to iron availability in cyanobacteria, SINAL 2010, Faro, Portugal (Abstract)