The defining characteristic of systems biology is that it seeks to develop a systems view of biology as opposed to a components view. This project aims to develop?in a feedback cycle that guides further experimentation?predictive computational models that capture the overall dynamics of the molecular network that underlies the shift of Neurospora from mycelia growth to asexual spore development through conidiation. Initial efforts will be directed towards construction of a predictive model for regulatory networks and correlation of this network with existing and new transcriptome and genomic data. This model will be tested and refined through incorporation of new data arising from Project 3 and, most importantly, via perturbation tests facilitated through the use of strains developed in Project 1 and characterized using the tools employed in Project 3. In addition, we will develop a comprehensive model of steady state metabolism in Neurospora and, by combining this model with our regulatory network model, make testable predictions about metabolic state corresponding to different gene expression states

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Program Projects (P01)
Project #
5P01GM068087-10
Application #
8466988
Study Section
Special Emphasis Panel (ZRG1-GGG-M)
Project Start
Project End
Budget Start
2013-04-01
Budget End
2014-03-31
Support Year
10
Fiscal Year
2013
Total Cost
$355,110
Indirect Cost
$44,305
Name
Dartmouth College
Department
Type
DUNS #
041027822
City
Hanover
State
NH
Country
United States
Zip Code
03755
Fuller, Kevin K; Loros, Jennifer J; Dunlap, Jay C (2015) Fungal photobiology: visible light as a signal for stress, space and time. Curr Genet 61:275-88
De Souza, Colin P; Hashmi, Shahr B; Osmani, Aysha H et al. (2014) Application of a new dual localization-affinity purification tag reveals novel aspects of protein kinase biology in Aspergillus nidulans. PLoS One 9:e90911
Gooch, Van D; Johnson, Alicia E; Bourne, Brian J et al. (2014) A kinetic study of the effects of light on circadian rhythmicity of the frq promoter of Neurospora crassa. J Biol Rhythms 29:38-48
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Dettmann, Anne; Heilig, Yvonne; Valerius, Oliver et al. (2014) Fungal communication requires the MAK-2 pathway elements STE-20 and RAS-2, the NRC-1 adapter STE-50 and the MAP kinase scaffold HAM-5. PLoS Genet 10:e1004762
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Samarajeewa, Dilini A; Sauls, Pegan A; Sharp, Kevin J et al. (2014) Efficient detection of unpaired DNA requires a member of the rad54-like family of homologous recombination proteins. Genetics 198:895-904
Fu, Ci; Tanaka, Asuma; Free, Stephen J (2014) Neurospora crassa 1,3-?-glucan synthase, AGS-1, is required for cell wall biosynthesis during macroconidia development. Microbiology 160:1618-27
Gooch, Van D; Johnson, Alicia E; Larrondo, Luis F et al. (2014) Bright to dim oscillatory response of the Neurospora circadian oscillator. J Biol Rhythms 29:49-59
Chinnici, Jennifer L; Fu, Ci; Caccamise, Lauren M et al. (2014) Neurospora crassa female development requires the PACC and other signal transduction pathways, transcription factors, chromatin remodeling, cell-to-cell fusion, and autophagy. PLoS One 9:e110603

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