About the Project
The ability to respond and adapt to the environment is crucial to all living organisms. Fungi have evolved the ability to adapt to a vast range of environmental parameters including temperature, elevated carbon dioxide concentrations, hypoxia, reactive oxygen species, quorum sensing molecules, pH and nutrient limitation. The response to such environmental signals is governed through a number of partially characterised signal transduction pathways including mitogen activated protein kinase (MAPK), cAMP dependent PKA, and specialised signalling cascades (i.e. Rim101). In their natural surroundings, these organisms are exposed to multiple environmental parameters at any given time. Currently, our knowledge of the molecular mechanisms used to adapt to changes in the environment are limited to individual parameters, and do not consider the combinatorial environments that actually occur. Using Candida glabrata as a model system, this project will elucidate how yeast respond and adapt to multiple environmental signals. Our focus is on how fungi respond to combinatorial environments that fluctuate in carbon dioxide levels, quorum sensing molecules, pH and nutrient limitation, and the consequence adaptation to these environments has on the fungus and its cell wall. Combining cutting edge molecular, transcriptomic, proteomic and metabolomic techniques with systems biology approaches, this project will identify the signal transduction network(s) used to orchestrate responses to complex multifactorial environments.
References
Cottier F, Leewattanapasuk W, Kemp LR, Murphy M, Supuran CT, Kurzai O, Mühlschlegel FA. (2013). Carbonic anhydrase regulation and CO(2) sensing in the fungal pathogen Candida glabrata involves a novel Rca1p ortholog. Bioorg Med Chem. 21, 1549-54
Kaloriti D, Tillmann A, Cook E, Jacobsen M, You T, Lenardon M, Ames L, Barahona M, Chandrasekaran K, Coghill G, Goodman D, Gow NA, Grebogi C, Ho HL, Ingram P, McDonagh A, de Moura AP, Pang W, Puttnam M, Radmaneshfar E, Romano MC, Silk D, Stark J, Stumpf M, Thiel M, Thorne T, Usher J, Yin Z, Haynes K, Brown AJ. (2012) Combinatorial stresses kill pathogenic Candida species. Med Mycol. 50, 699-709.
You T, Ingram P, Jacobsen MD, Cook E, McDonagh A, Thorne T, Lenardon MD, de Moura AP, Romano MC, Thiel M, Stumpf M, Gow NA, Haynes K, Grebogi C, Stark J, Brown A. (2012). A systems biology analysis of long and short-term memories of osmotic stress adaptation in fungi. BMC Res Notes. 25 258
Jabbari S., Heap J.T., King J.R. (2011) Mathematical modelling of the sporulation-initiation network in Bacillus subtilis revealing the dual role of the putative quorum-sensing signal molecule PhrA. Bull. Math. Biol., 73:181-211.
Hall RA, Turner KJ, Chaloupka J, Cottier F, De Sordi L, Sanglard D, Levin LR, Buck J, Mühlschlegel FA (2011). The quorum-sensing molecules farnesol/homoserine lactone and dodecanol operate via distinct modes of action in Candida albicans. Eukaryot. Cell, 10, 1034-1042.
Hall RA, De Sordi L, Maccallum DM, Topal H, Eaton R, Bloor JW, Robinson GK, Levin LR, Buck J, Wang Y, Gow NA, Steegborn C, Mühlschlegel FA. (2010). CO(2) acts as a signalling molecule in populations of the fungal pathogen Candida albicans. PLoS Pathog., 6 :e1001193.
Hall RA, Cottier F, Mühlschlegel FA (2009). Molecular networks in the pathogen Candida albicans. Advan. Applied Microbiol., 67, 191-212
Stead D, Findon H, Yin Z, Walker J, Selway L, Cash P, Dujon BA, Hennequin C, Brown AJ, Haynes K. (2005). Proteomic changes associated with inactivation of the Candida glabrata ACE2 virulence-moderating gene. Proteomics. 5, 1838-48.
Continue with Facebook
