Proteomic Identification of Novel Regulators and Effectors of Osmoadaptation and Autophagy of Model Filamentous Fungi Aspergillus nidulans

Title	Proteomic Identification of Novel Regulators and Effectors of Osmoadaptation and Autophagy of Model Filamentous Fungi Aspergillus nidulans
Author	Kim, Yonghyun
Advisors	Marten, Mark R
Program	Engineering, Chemical and Biochemical
UMBC Department	Chemical and Biochemical Engineering
Document Type	dissertation
Sponsors	University of Maryland, Baltimore County (UMBC)
Keywords	Autophagy; Carbon-starvation; Filamentous Fungi; Osmoadaptation; Proteomics; Rapamycin; Engineering, Chemical (0542); Biology, Molecular (0307); Biology, Microbiology (0410)
Date Issued	2008-01-01; *
Abstract	The Aspergilli are important filamentous fungi to study, being simultaneously both extremely helpful and harmful to human. Here, we characterize the proteomics of the model fungus Aspergillus nidulans during autophagy, a key cellular process which, when strategically manipulated, can help harness the benefits of fungi and downplay their detrimental effects. Autophagy (more specifically, macroautophagy) is an important cellular mechanism by which cells degrade and recycle portions of the cytosol when there is limited nutrient supply. Autophagy is highly conserved from yeast to man, and thus our study here have broad implications to all eukaryotes. Currently, only a few studies exist that characterized autophagy in fungi. We thus employed proteomic analysis, a systems biology tool which provides a panoptic, large-scale profiling of protein expression level changes, to better understand fungal autophagy. Thus, the broad goal here is to utilize proteomic analysis to develop a better fundamental understanding of protein expression associated with autophagy in filamentous fungi. We first established one of the first A. nidulans proteome map. Osmoadaptation, a relatively better understood stress response than autophagy, was used to validate our proteomic approach. Our analysis also identified novel proteins that are implicated for the first time to be linked with osmoadaptation. Next, we studied the proteomic difference between two known inducers of autophagy, carbon-starvation and rapamycin treatment. Our data suggests that some effectors are shared between the rapamycin-regulated pathways and carbon-starvation regulated pathways (e.g. polar growth, cell wall degradation), that the mechanism by which they are regulated are different (e.g. 14-3-3 ArtA involved in regulating polar growth during carbon-starvation but not during rapamycin treatment), and that there are other effectors that are distinct between the two (e.g. reduced amino acid biosynthesis only observed in carbon-starvation). Our final study builds on this theme by reporting a time-dependent response of autophagy-impaired mutant (ΔAtg8) exposed to rapamycin. Our proteomic data suggest that A. nidulans, when challenged with rapamycin, upregulates gluconeogenesis, pentose phosphate pathway, amino acid biosynthesis, secretory pathway, polarized growth, and ribosome turnover even without a fully functioning autophagy. Taken together, our proteomic data imply that rapamycin-mediated effectors are distinguished from those of autophagy.
Identifier	10050
Format	application:pdf
Language	en
Collection	UMBC Theses and Dissertations
Rights Statement	This item may be protected under Title 17 of the U.S. Copyright Law. It is made available by UMBC for non-commercial research and education. For permission to publish or reproduce, please see http://aok.lib.umbc.edu/specoll/repro.php or contact Special Collections at speccoll(at)umbc.edu.

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Proteomic Identification of Novel Regulators and Effectors of Osmoadaptation and Autophagy of Model Filamentous Fungi Aspergillus nidulans

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