Towards a systems model of circadian control of gene function to regulate metabolic phenotype and cellulase production in Neurospora crassa
EMSL Project ID
51318
Abstract
Biofuel production using cellulases extracted from fungi has the potential to be a major resource to replace fossil fuels, and regulating the synthesis of these and other enzymes is crucial for the economics of biofuel production from lignocellulose. Some of the best producers of plant cell wall-degrading enzymes are filamentous fungi. However, environmental controls on cellular metabolism are known to modulate the amount of cellulases that can be produced in fungi. The filamentous fungus Neurospora is used both in the production of cellulases for biofuel manufacture and as a model for other fungal cellulase production systems. It is also the principal fungal model system for the study of the effects of light and circadian clocks. The circadian clock plays a large role in the regulation of the Neurospora genome: as many as 40% of Neurospora transcripts and 30% of Neurospora proteins are clock regulated, including many genes that regulate metabolism. Although the dominant general role of the clock in metabolic regulation is appreciated, the degree to which the clock controls specific aspects of metabolism is not currently understood.
The long-term goals of our project are to identify the link between time of day and cellulase levels in an effort to better understand their regulation and increase the manufacture of these important components for energy production. To do so, we will incorporate large-scale data gathered in this and previous grants to create a multi-scale model of circadian regulation over cellular metabolism to determine avenues by which Neurospora or other fungi could be modified to increase cellulase production. In addition, in so far as clocks have been described in many phyla within the fungal kingdom including basidiomycetes, understanding circadian control of metabolism in Neurospora will contribute broadly to understanding metabolic control of cellulases in many important species including common wood-rotting and ectomycorrhizal fungi.
To understand the role that the circadian clock plays in regulating cellular metabolism, more specifically the regulation of cellulases, we will assess circadian regulation broadly in Neurospora, gathering data on rates of translation, degradation, acetylation, metabolic oscillations, and transcription factor activity. All of these data (proteome, ribosome profiles, transcription factor network, and metabolome) will be used for computational modeling of the metabolome and cellulose utilization in Neurospora. To carry out all of these aims, we will rely on the technical abilities of EMSL, cutting-edge MS analysis , EMSL sequencing capabilities, and computing resources. Our labs will use commonly applied informatic and statistical analyses to determine which elements are rhythmic and the degree to which post-translational regulation affects circadian control of metabolic output. We believe that the success of the overarching goal of this project, the multi-scale model of the circadian clock and metabolism, will provide insights into whether and how to decouple metabolism from the clock, with the goal of increasing the production of cellulases in fungi for use in biofuel manufacture.
Project Details
Project type
Large-Scale EMSL Research
Start Date
2020-10-01
End Date
2022-09-30
Status
Closed
Released Data Link
Team
Principal Investigator
Co-Investigator(s)
Team Members