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Malcolm Whiteway  - - - 
Top co-authors
Cunle Wu

8 shared publications

Division of Experimental Medicine, Department of Medicine, McGill University, Montreal, QC H4A 3J1, Canada

Adnane Sellam

7 shared publications

University Laval

Faiza Tebbji

7 shared publications

Infectious Diseases Research Centre-CRI, CHU de Québec Research Center (CHUQ), Université Laval, Quebec City, Quebec, Canada

25
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Publication Record
Distribution of Articles published per year 
(2007 - 2019)
Total number of journals
published in
 
18
 
Publications See all
Article 2 Reads 0 Citations The adaptor protein Ste50 directly modulates yeast MAPK signaling specificity through differential connections of its RA... Nusrat Sharmeen, Traian Sulea, Malcolm Whiteway, Cunle Wu Published: 15 March 2019
Molecular Biology of the Cell, doi: 10.1091/mbc.e18-11-0708
DOI See at publisher website
Article 0 Reads 0 Citations MAP Kinase Regulation of the Candida albicans Pheromone Pathway Golnaz Rastghalam, Raha Parvizi Omran, Masoumeh Alizadeh, De... Published: 20 February 2019
mSphere, doi: 10.1128/msphere.00598-18
DOI See at publisher website PubMed View at PubMed ABS Show/hide abstract
MAP kinases and their regulators are critical components of eukaryotic signaling pathways implicated in normal cell behavior as well as abnormal behaviors linked to diseases such as cancer. The mating pathway of the yeast Saccharomyces cerevisiae was central in establishing the MAP kinase paradigm. Here we investigate the mating pathway in a different ascomycete, the fungal pathogen C. albicans. In this dimorphic fungus MAP kinases are also implicated in the mating response, with two MAP kinases apparently playing redundant roles in the mating process. This work establishes that while some level of mating can occur in the presence of a single kinase, the Cek1 kinase is most important for mating, while the Cek2 kinase is involved in adaptation to signaling. While both kinases appear to be themselves regulated by dephosphorylation through the action of the Cpp1 phosphatase, this process appears important for mating only in the case of Cek1.
Article 0 Reads 0 Citations Functional divergence of a global regulatory complex governing fungal filamentation Elizabeth J. Polvi, Amanda O. Veri, Zhongle Liu, Saif Hossai... Published: 07 January 2019
PLOS Genetics, doi: 10.1371/journal.pgen.1007901
DOI See at publisher website PubMed View at PubMed ABS Show/hide abstract
Morphogenetic transitions are prevalent in the fungal kingdom. For a leading human fungal pathogen, Candida albicans, the capacity to transition between yeast and filaments is key for virulence. For the model yeast Saccharomyces cerevisiae, filamentation enables nutrient acquisition. A recent functional genomic screen in S. cerevisiae identified Mfg1 as a regulator of morphogenesis that acts in complex with Flo8 and Mss11 to mediate transcriptional responses crucial for filamentation. In C. albicans, Mfg1 also interacts physically with Flo8 and Mss11 and is critical for filamentation in response to diverse cues, but the mechanisms through which it regulates morphogenesis remained elusive. Here, we explored the consequences of perturbation of Mfg1, Flo8, and Mss11 on C. albicans morphogenesis, and identified functional divergence of complex members. We observed that C. albicans Mss11 was dispensable for filamentation, and that overexpression of FLO8 caused constitutive filamentation even in the absence of Mfg1. Harnessing transcriptional profiling and chromatin immunoprecipitation coupled to microarray analysis, we identified divergence between transcriptional targets of Flo8 and Mfg1 in C. albicans. We also established that Flo8 and Mfg1 cooperatively bind to promoters of key regulators of filamentation, including TEC1, for which overexpression was sufficient to restore filamentation in the absence of Flo8 or Mfg1. To further explore the circuitry through which Mfg1 regulates morphogenesis, we employed a novel strategy to select for mutations that restore filamentation in the absence of Mfg1. Whole genome sequencing of filamentation-competent mutants revealed chromosome 6 amplification as a conserved adaptive mechanism. A key determinant of the chromosome 6 amplification is FLO8, as deletion of one allele blocked morphogenesis, and chromosome 6 was not amplified in evolved lineages for which FLO8 was re-located to a different chromosome. Thus, this work highlights rewiring of key morphogenetic regulators over evolutionary time and aneuploidy as an adaptive mechanism driving fungal morphogenesis. Fungal infections pose a severe burden to human health worldwide. Candida albicans is a leading cause of systemic fungal infections, with mortality rates approaching 40%. One of the key virulence traits of this fungus is its ability to transition between yeast and filamentous forms in response to diverse host-relevant cues. The model yeast Saccharomyces cerevisiae is also capable of filamentous growth in certain conditions, and previous work has identified a key transcriptional complex required for filamentation in both species. However, here we discover that the circuitry governed by this complex in C. albicans is largely distinct from that in the non-pathogenic S. cerevisiae. We also employ a novel selection strategy to perform experimental evolution, identifying chromosome triplication as a mechanism to restore filamentation in a non-filamentous...
Article 0 Reads 0 Citations Mms21: A Putative SUMO E3 Ligase in Candida albicans That Negatively Regulates Invasiveness and Filamentation, and Is Re... Amjad Islam, Faiza Tebbji, Jaideep Mallick, Hannah Regan, Va... Published: 07 December 2018
Genetics, doi: 10.1534/genetics.118.301769
DOI See at publisher website
Article 0 Reads 1 Citation Evolutionary Transition of GAL Regulatory Circuit from Generalist to Specialist Function in Ascomycetes Baharul I. Choudhury, Malcolm Whiteway Published: 01 August 2018
Trends in Microbiology, doi: 10.1016/j.tim.2017.12.008
DOI See at publisher website
Article 0 Reads 3 Citations Tuning Hsf1 levels drives distinct fungal morphogenetic programs with depletion impairing Hsp90 function and overexpress... Amanda O. Veri, Zhengqiang Miao, Rebecca S. Shapiro, Faiza T... Published: 28 March 2018
PLOS Genetics, doi: 10.1371/journal.pgen.1007270
DOI See at publisher website PubMed View at PubMed ABS Show/hide abstract
The capacity to respond to temperature fluctuations is critical for microorganisms to survive within mammalian hosts, and temperature modulates virulence traits of diverse pathogens. One key temperature-dependent virulence trait of the fungal pathogen Candida albicans is its ability to transition from yeast to filamentous growth, which is induced by environmental cues at host physiological temperature. A key regulator of temperature-dependent morphogenesis is the molecular chaperone Hsp90, which has complex functional relationships with the transcription factor Hsf1. Although Hsf1 controls global transcriptional remodeling in response to heat shock, its impact on morphogenesis remains unknown. Here, we establish an intriguing paradigm whereby overexpression or depletion of C. albicans HSF1 induces morphogenesis in the absence of external cues. HSF1 depletion compromises Hsp90 function, thereby driving filamentation. HSF1 overexpression does not impact Hsp90 function, but rather induces a dose-dependent expansion of Hsf1 direct targets that drives overexpression of positive regulators of filamentation, including Brg1 and Ume6, thereby bypassing the requirement for elevated temperature during morphogenesis. This work provides new insight into Hsf1-mediated environmentally contingent transcriptional control, implicates Hsf1 in regulation of a key virulence trait, and highlights fascinating biology whereby either overexpression or depletion of a single cellular regulator induces a profound developmental transition.
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