The central goal of the three interdependent efforts in this Program Project builds upon successful functional genomics, annotation, and expression analyses of Neurospora crassa, a premier filamentous Fungus model for over 250,000 species of non-yeast fungi. A primary goal, targeted through molecular, cell biological, genomic and computational approaches, will be to understand how N. crassa transitions from mycelial growth to complete asexual spore development. We will focus on two key triggers of asexual development: light and desiccation. In addition, we will leverage our prior successes to expand systematic knockouts to an additional prominent model system, Aspergillus nidulans. Neurospora is a salient model for basic research in eukaryotes, as is Aspergillus, and fungi allied to these species include most animal and plant pathogens as well as industrial strains yielding antibiotics, chemicals, enzymes, and Pharmaceuticals. Gene predictions among the 9846 genes encoded by the fully sequenced 43 Mb Neurospora genome are supported by over 250,000 ESTs derived from this P01. During the past 4 years, we revolutionized the tools and techniques for gene knockouts in filamentous fungi and exceeded our initial goal by over 40%. Project #1 will complete the Neurospora gene knockouts and extend the systematic disruption of genes to Aspergillus. We will develop strains, tools, and background information in support of Projects #2 and #3, and of the overarching goal of understanding regulatory pathways governing filamentous fungal development. Projects #2 and #3 will aim to describe and reconstruct the cascading regulatory programs that underlie N. crassa's developmental response to light and air, from the level of chromatin structure through the gene regulatory network. Project #3 will use ChlP-seq mapping of histone modifications, transcription factor binding sites, sites of DNA methylation and nucleosome occupancy with corresponding transcriptome measurements to generate a deep description of genome and epigenome dynamics. Project #2, in an informatic-intensive systems biology approach, will integrate these data and use computational modeling to develop predictive models of the interconnected light and asexual development gene regulatory networks. These models will be fleshed out tested through incorporation of new data arising from Project #3 and refined via perturbation analyses facilitated through the use of strains developed in Project #1 and characterized using the tools employed in Project #3. This effort will anchor, promote, and exploit genomic exploration within model systems that provide gateways to the Kingdom of the Fungi.
Filamentous fungi, typically known as molds, are common animal and plant pathogens, but they are also widely used as industrial strains to provide antibiotics, chemicals, enzymes, and Pharmaceuticals. We'd be dead without them but they can kill us. We seek to understand how genes and proteins work together to regulate fungal growth and development, so as to enhance the good things and control the bad things produced by fungi.
|Qiu, Rongde; Zhang, Jun; Xiang, Xin (2018) p25 of the dynactin complex plays a dual role in cargo binding and dynactin regulation. J Biol Chem 293:15606-15619|
|Heller, Jens; Clavé, Corinne; Gladieux, Pierre et al. (2018) NLR surveillance of essential SEC-9 SNARE proteins induces programmed cell death upon allorecognition in filamentous fungi. Proc Natl Acad Sci U S A 115:E2292-E2301|
|Wang, Zheng; Wang, Junrui; Li, Ning et al. (2018) Light sensing by opsins and fungal ecology: NOP-1 modulates entry into sexual reproduction in response to environmental cues. Mol Ecol 27:216-232|
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|Serrano, Antonio; Illgen, Julia; Brandt, Ulrike et al. (2018) Spatio-temporal MAPK dynamics mediate cell behavior coordination during fungal somatic cell fusion. J Cell Sci 131:|
|De Souza, Colin P; Hashmi, Shahr B; Hage, Natalie et al. (2017) Location and functional analysis of the Aspergillus nidulans Aurora kinase confirm mitotic functions and suggest non-mitotic roles. Fungal Genet Biol 103:1-15|
|Decker, Logan M; Xiao, Hua; Boone, Erin C et al. (2017) The Nuclear Cap-Binding Complex Mediates Meiotic Silencing by Unpaired DNA. G3 (Bethesda) 7:1149-1155|
|Samarajeewa, Dilini A; Manitchotpisit, Pennapa; Henderson, Miranda et al. (2017) An RNA Recognition Motif-Containing Protein Functions in Meiotic Silencing by Unpaired DNA. G3 (Bethesda) 7:2871-2882|
|Havlik, David; Brandt, Ulrike; Bohle, Kathrin et al. (2017) Establishment of Neurospora crassa as a host for heterologous protein production using a human antibody fragment as a model product. Microb Cell Fact 16:128|
|Ivanov, Ivaylo P; Wei, Jiajie; Caster, Stephen Z et al. (2017) Translation Initiation from Conserved Non-AUG Codons Provides Additional Layers of Regulation and Coding Capacity. MBio 8:|
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