Enabling a Community to Dissect an Organism: Overview of the Neurospora Functional Genomics Project

Dunlap, Jay C.; Borkovich, Katherine A.; Henn, Matthew R.; Turner, Gloria E.; Sachs, Matthew S.; Glass, N. Louise; McCluskey, Kevin; Plamann, Michael; Galagan, James E.; Birren, Bruce W.; Weiss, Richard L.; Townsend, Jeffrey P.; Loros, Jennifer J.; Nelson, Mary Anne; Lambreghts, Randy; Colot, Hildur V.; Park, Gyungsoon; Collopy, Patrick D.; Ringelberg, Carol S.; Crew, Christopher M.; Litvinkova, Liubov; DeCaprio, David; Hood, Heather M.; Curilla, Susan; Shi, Mi; Crawford, Matthew E.; Koerhsen, Michael; Montgomery, Phil; Larson, Lisa M.; Pearson, Matthew D.; Kasuga, Takao; Tian, Chaoguang; Baştürkmen, Meray; Altamirano, Lorena; Xu, Jianguo

doi:10.1016/s0065-2660(06)57002-6

Cited by 198 publications

(199 citation statements)

References 71 publications

(72 reference statements)

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“…We therefore tested the PHS sensitivity of available mutants (Colot et al, 2006;Dunlap et al, 2007;McCluskey, 2003) that carried deletions in genes whose expression was affected (either increased or decreased) by exposure to PHS. Germinating conidia from most of them displayed no altered sensitivity to PHS.…”

Section: Discussionmentioning

confidence: 99%

“…Consequently, mutant strains carrying deletions in relevant genes might respond differently to PHS than the wild-type strain. To verify this, we took advantage of an ongoing project to disrupt all N. crassa genes (Colot et al, 2006;Dunlap et al, 2007) and tested the sensitivity to PHS of several available deletion mutants in spot assays. Serial dilutions of conidia from the different strains were exposed to media containing PHS (Fig.…”

Section: Sensitivity Of Selected Deletion Mutants To Phsmentioning

confidence: 99%

“…We use the filamentous fungus Neurospora crassa as a model organism because it offers many experimental advantages (Davis & Perkins, 2002;Dunlap et al, 2007) and PCD can be induced by different means (Castro et al, 2008;Glass & Dementhon, 2006;Lu, 2006). Moreover, the ongoing project for the disruption of all predicted genes in the N. crassa genome (Colot et al, 2006) allows direct testing of the sensitivity of specific mutants to PCDinducing stimuli, including mutants in genes identified by expression profiling.…”

Section: Introductionmentioning

confidence: 99%

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Transcriptional analysis of the response of Neurospora crassa to phytosphingosine reveals links to mitochondrial function

et al. 2009

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Treatment of Neurospora crassa cells with phytosphingosine (PHS) induces programmed cell death (PCD) by an unknown mechanism. To determine the relationship between PHS treatment and PCD, we determined changes in global gene expression levels in N. crassa during a time-course of PHS treatment. Most genes having differential expression levels compared to untreated samples showed an increase in relative expression level upon PHS exposure. However, genes encoding mitochondrial proteins were highly enriched among~100 genes that showed a relative decrease in expression levels after PHS treatment, suggesting that repression of these genes might be related to the death-inducing effects of PHS. Since mutants in respiratory chain complex I are more resistant to both PHS and hydrogen peroxide (H 2 O 2 ) than the wild-type strain, possibly related to the production of reactive oxygen species, we also compared gene expression profiles of a complex I mutant (nuo14) and wild-type in response to H 2 O 2 . Genes with higher expression levels in the mutant, in the presence of H 2 O 2 , are also significantly enriched in genes encoding mitochondrial proteins. These data suggest that complex I mutants cope better with drug-induced decrease in expression of genes encoding mitochondrial proteins and may explain their increased resistance to both PHS and H 2 O 2 . As a way of identifying new components required for PHS-induced death, we analysed the PHS sensitivity of 24 strains carrying deletions in genes that showed a significant alteration in expression pattern when the wild-type was exposed to the sphingolipid. Two additional mutants showing increased resistance to PHS were identified and both encode predicted mitochondrial proteins, further supporting the role of the mitochondria in PHS-induced PCD. INTRODUCTIONIn response to endogenous or external stimuli, living cells can undergo a genetic programme eventually leading to death, commonly known as programmed cell death (PCD). This suicide process can take several forms (apoptosis, necrosis, autophagy), each of which displays typical characteristics at both the cellular and molecular level. These processes can be interchangeable and are sometimes difficult to distinguish. In metazoan organisms, the death programme is essential for development and its dysfunction may result in human disease, such as cancer. In addition to multicellular eukaryotic species, both prokaryotic and eukaryotic unicellular organisms also undergo PCD (Cheng et al., 2008;Green & Kroemer, 2004;Hamann et al., 2008;Madeo et al., 2004).Mitochondria are cellular organelles, still possessing their own genome, that are responsible for the production of most cellular energy in eukaryotes. This production occurs mainly in the mitochondrial inner membrane through the process of oxidative phosphorylation, which involves the components of the respiratory chain and ATP synthase (Hatefi, 1985). The involvement of mitochondria and specific mitochondrial proteins, particularly components of the respiratory chain, in most ca...

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Section: Discussionmentioning

confidence: 99%

Section: Sensitivity Of Selected Deletion Mutants To Phsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Transcriptional analysis of the response of Neurospora crassa to phytosphingosine reveals links to mitochondrial function

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“…The N. crassa genome is predicted to contain twice as many cellulases as H. jecorina (11), as well as many hemicellulases and other enzymes involved in plant biomass degradation. Genetic and molecular tools to manipulate N. crassa are extensive (5) as are genomic resources, including whole genome microarrays and a near-full genome deletion strain set (12). N. crassa is the only example of a model organism that also happens to be a proficient degrader of plant cell walls.…”

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confidence: 99%

Systems analysis of plant cell wall degradation by the model filamentous fungus Neurospora crassa

Tian

Beeson

Iavarone

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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The filamentous fungus Neurospora crassa is a model laboratory organism, but in nature is commonly found growing on dead plant material, particularly grasses. Using functional genomics resources available for N. crassa, which include a near-full genome deletion strain set and whole genome microarrays, we undertook a systemwide analysis of plant cell wall and cellulose degradation. We identified approximately 770 genes that showed expression differences when N. crassa was cultured on ground Miscanthus stems as a sole carbon source. An overlap set of 114 genes was identified from expression analysis of N. crassa grown on pure cellulose. Functional annotation of up-regulated genes showed enrichment for proteins predicted to be involved in plant cell wall degradation, but also many genes encoding proteins of unknown function. As a complement to expression data, the secretome associated with N. crassa growth on Miscanthus and cellulose was determined using a shotgun proteomics approach. Over 50 proteins were identified, including 10 of the 23 predicted N. crassa cellulases. Strains containing deletions in genes encoding 16 proteins detected in both the microarray and mass spectrometry experiments were analyzed for phenotypic changes during growth on crystalline cellulose and for cellulase activity. While growth of some of the deletion strains on cellulose was severely diminished, other deletion strains produced higher levels of extracellular proteins that showed increased cellulase activity. These results show that the powerful tools available in N. crassa allow for a comprehensive system level understanding of plant cell wall degradation mechanisms used by a ubiquitous filamentous fungus.cellulase ͉ secretome ͉ transcriptome

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“…Similarly, the development of molecular tools for manipulating strains, including gene knockouts, auxotrophic mutants and complementary plasmids, and strains deficient in non-homologous end-joining allowing targeted transformation (Schuster et al 2012) has meant that Trichoderma is as easily manipulated as historical model systems such as N. crassa (Dunlap et al 2007) and A. nidulans . To that end, diverse T. reesei strains are available from public collections.…”

Section: Pathogenic Aspergillimentioning

confidence: 99%

Diverse data supports the transition of filamentous fungal model organisms into the post-genomics era

McCluskey

Baker

2017

Mycology

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Filamentous fungi have been important as model organisms since the beginning of modern biological inquiry and have benefitted from open data since the earliest genetic maps were shared. From early origins in simple Mendelian genetics of mating types, parasexual genetics of colony colour, and the foundational demonstration of the segregation of a nutritional requirement, the contribution of research systems utilising filamentous fungi has spanned the biochemical genetics era, through the molecular genetics era, and now are at the very foundation of diverse omics approaches to research and development. Fungal model organisms have come from most major taxonomic groups although Ascomycete filamentous fungi have seen the most major sustained effort. In addition to the published material about filamentous fungi, shared molecular tools have found application in every area of fungal biology. Similarly, shared data has contributed to the success of model systems. The scale of data supporting research with filamentous fungi has grown by 10 to 12 orders of magnitude. From genetic to molecular maps, expression databases, and finally genome resources, the open and collaborative nature of the research communities has assured that the rising tide of data has lifted all of the research systems together.

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Enabling a Community to Dissect an Organism: Overview of the Neurospora Functional Genomics Project

Cited by 198 publications

References 71 publications

Transcriptional analysis of the response of Neurospora crassa to phytosphingosine reveals links to mitochondrial function

Transcriptional analysis of the response of Neurospora crassa to phytosphingosine reveals links to mitochondrial function

Systems analysis of plant cell wall degradation by the model filamentous fungus Neurospora crassa

Diverse data supports the transition of filamentous fungal model organisms into the post-genomics era

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