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Table of contents
1 Candida glabrata, a yeast with many faces
1.1 A hectic phylogenetic classification
1.2 Close to Saccharomyces spp, far from Candida spp ?
1.3 An « emerging » opportunistic pathogen
1.4 C. glabrata genome plasticity : a huge impact
1.5 Breaking C. glabrata clichés
1.5.1 A commensal yeast ?
1.5.2 An asexual yeast
2 Candida glabrata and the stress responses
2.1 A general response : the Environmental Stress Response (ESR)
2.2 Condition-specific stress responses
2.2.1 Rox1, a mediator of response to hypoxia
2.2.2 The oxidative stress response (OSR)
2.2.3 The CCAAT-Binding Complex as a link between oxidative stress and respiration
2.2.4 The iron homeostasis is linked with respiration and oxidation
2.2.4.1 Response to iron-depleted media
2.2.4.2 Response to iron-excess
3 Candihub, the study of transcriptional networks of Candida glabrata stress responses
3.1 Networks : a model to represent connections between various elements
3.2 The transcriptional regulatory networks
3.3 The Candihub project : deciphering stress responses in Candida species using transcriptional regulatory networks
3.3.1 Description and goals of the Candihub project
3.3.2 Building the Candihub networks
3.3.2.1 Types of C. glabrata strains used in this work
3.3.2.1.1 DHTL strain
3.3.2.1.2 TF deleted strains
3.3.2.1.3 myc-tagged TF strains
3.3.2.2 Approaches to build networks
3.3.2.2.1 Mathematical inference of regulatory networks from experimental data
3.3.2.2.2 Direct determination of regulatory networks
3.3.3 Proof of concept of Candihub : the Yap network
3.3.4 Goals of my PhD
4 Stress responses in Candida glabrata : a highly interconnected network
4.1 Introduction
4.2 Selection of the ChIP conditions
4.3 Sequencing of the immuno-precipitated DNA
4.4 Peak-calling and identification of the targets
4.5 Representing the Candihub network
5 The CBC Impacts Respiratory Genes and Iron Homeostasis in Candida Glabrata
5.1 Introduction
5.2 Publication
5.3 Supplementary results
5.3.1 Introduction
5.3.2 The YRE and the CCAAT motifs are required to activate the iron excess response
5.3.3 The YRE and the CCAAT motifs are differentially conserved in the Saccharomycetales
5.3.4 Hap4 might still interact with the CBC during iron excess response
5.3.5 Conclusion
6 Comparative Transcriptomics Reveals New Features of Iron Starvation in Candida glabrata
6.1 Introduction
6.2 Publication
6.3 Supplementary results
6.3.1 Introduction
6.3.2 Aft1 network in Candida glabrata
6.3.3 C. glabrata Aft1 has several functions shared with S. cerevisiae Aft1
6.3.4 C. glabrata Aft1 and Aft2 roles are only partially redundant
6.3.5 Relationship between Aft factors in S. cerevisiae share some features with C. glabrata
6.3.6 Relationship between Aft factors in more distant species
6.3.7 GRX3 and GRX4 are involved in iron-deprivation response under different regulations
6.3.8 Conclusion
Conclusion and perspectives
