Environmental Molecular Sciences Laboratory

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Towards a metabolic model of circadian clock control of metabolism in Neurospora crassa.

Monday, October 1, 2018
Principal Investigator: 
Jennifer Hurley
Lead Institution: 
Rensselaer Polytechnic Institute
Project ID: 

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 commonly used in the production of cellulases for biofuel manufacture and 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 genes can be 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 improve 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 could be modified to increase cellulase production.
To understand the role that the circadian clock plays in regulating cellular metabolism, more specifically the regulation of cellulases, we will assess circadian post-transcriptional regulation in the cell, gathering data on rates of translation, degradation and transcription factor post-translational modification. In collaborative exploratory studies carried out at EMSL, all of these data (proteome, ribosome profiles, and metabolome) will be used for computational modeling of the metabolome and cellulose utilization. Moreover, we will take this goal a step further and create a model of how these circadian and metabolic elements impact the growth of Neurospora in a 3-dimensional space. To estimate the absolute metabolite concentrations necessary for the model, we will employ in Metabolic Flux Analysis (MFA) and need to assess the basic metabolite levels in Neurospora under MFA conditions. 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 hypothesize that 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 needed in biofuel manufacture.