Investigating Signaling Pathway Integration in Saccharomyces Cerevisiae on an Alternative Carbon Source to Coordinate Growth, Metabolism, and Stress Defense PDF Download
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Author: Ellen Renee Wagner
Publisher:
ISBN:
Category :
Languages : en
Pages : 0
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Book Description
Due to its relative ease, microbial engineering is invaluable for applied research focused on product formation, particularly for biofuel production. The budding yeast Saccharomyces cerevisiae is an ideal organism for biofuel-based engineering due to its genetic tractability, well researched biology, and preference for fermentation. Even with these advantages, two large bottlenecks for sustainable biofuel production remain. First, when lignocellulosic biomass is broken down, it releases several sugars, the majority being glucose and xylose. While many microorganisms, including yeast, can readily ferment glucose, they lack the ability to ferment the pentose sugar xylose. Second, the process of breaking down lignocellulosic material introduces toxic chemicals into the resulting hydrolysate. These toxins inhibit microbial growth and metabolism, specifically limiting pentose utilization in engineered strains. Through collaborative efforts, we identified loss-of-function mutations in the stress-responsive MAP kinase HOG1 and negative regulator of the RAS/Protein Kinase A (PKA) pathway, IRA2, among other minimal genetic changes, enhances anaerobic xylose fermentation. However, these mutations likely reduce cells' ability to tolerate the toxins present in lignocellulosic hydrolysate, making the strain especially vulnerable to it. As these mutations impact broadly acting signaling networks, the physiological changes required for robust xylose fermentation are unclear. Previously, we generated a strain capable of rapid xylose fermentation with minimal growth by deleting the PKA regulatory subunit BCY1 in the presence of wildtype IRA2 and HOG1. Past work found these strains co-activate the alternative carbon source Snf1 pathway with the PKA pathway to enable xylose utilization. This present a unique model in which to study the integration of three highly conserved signaling pathways for the utilization of a non-native carbon source in the presence of environmental stressors. In chapter 2, we test the contributions of Hog1 and PKA signaling via IRA2 or BCY1 to metabolism, growth, and stress tolerance in mixed sugar media. In chapter 3, we use a multi-omics approach to develop models for how cells coordinate growth, metabolism, and other responses in budding yeast and how restructuring these processes enables anaerobic xylose utilization.
Author: Ellen Renee Wagner
Publisher:
ISBN:
Category :
Languages : en
Pages : 0
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Book Description
Due to its relative ease, microbial engineering is invaluable for applied research focused on product formation, particularly for biofuel production. The budding yeast Saccharomyces cerevisiae is an ideal organism for biofuel-based engineering due to its genetic tractability, well researched biology, and preference for fermentation. Even with these advantages, two large bottlenecks for sustainable biofuel production remain. First, when lignocellulosic biomass is broken down, it releases several sugars, the majority being glucose and xylose. While many microorganisms, including yeast, can readily ferment glucose, they lack the ability to ferment the pentose sugar xylose. Second, the process of breaking down lignocellulosic material introduces toxic chemicals into the resulting hydrolysate. These toxins inhibit microbial growth and metabolism, specifically limiting pentose utilization in engineered strains. Through collaborative efforts, we identified loss-of-function mutations in the stress-responsive MAP kinase HOG1 and negative regulator of the RAS/Protein Kinase A (PKA) pathway, IRA2, among other minimal genetic changes, enhances anaerobic xylose fermentation. However, these mutations likely reduce cells' ability to tolerate the toxins present in lignocellulosic hydrolysate, making the strain especially vulnerable to it. As these mutations impact broadly acting signaling networks, the physiological changes required for robust xylose fermentation are unclear. Previously, we generated a strain capable of rapid xylose fermentation with minimal growth by deleting the PKA regulatory subunit BCY1 in the presence of wildtype IRA2 and HOG1. Past work found these strains co-activate the alternative carbon source Snf1 pathway with the PKA pathway to enable xylose utilization. This present a unique model in which to study the integration of three highly conserved signaling pathways for the utilization of a non-native carbon source in the presence of environmental stressors. In chapter 2, we test the contributions of Hog1 and PKA signaling via IRA2 or BCY1 to metabolism, growth, and stress tolerance in mixed sugar media. In chapter 3, we use a multi-omics approach to develop models for how cells coordinate growth, metabolism, and other responses in budding yeast and how restructuring these processes enables anaerobic xylose utilization.
Author: Matthew Edward MacGilvray
Publisher:
ISBN:
Category :
Languages : en
Pages : 0
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Book Description
Cells respond to stressful conditions by coordinating a complex, multi-faceted response that spans many levels of physiology. Much of the response is coordinated by changes in protein phosphorylation. Although the regulators of transcriptome changes during stress are well characterized in Saccharomyces cerevisiae, the upstream regulatory network controlling protein phosphorylation is less well dissected. In this thesis, we developed a computational approach to infer the stress-activated signaling network that regulates phosphorylation changes in response to salt stress and the ER stressor dithiothreitol (DTT). The method uses integer linear programming (ILP) to integrate stress-responsive phospho-proteome responses in wild-type and mutant strains, predicted phosphorylation motifs on groups of coregulated peptides, and published protein interaction data. The inferred salt-network predicted new regulatory connections between stress-activated and growth-regulating pathways and suggested mechanisms coordinating metabolism, cell-cycle progression, and growth during stress. Further, kinase inference during DTT suggested new functions for the HOG and PKA pathways in augmenting the unfolded protein response (UPR). Together, our work shows how a high-quality computational network model can facilitate discovery of new pathway interactions during diverse stress responses.
Author: Stefan Hohmann
Publisher: Springer Science & Business Media
ISBN: 3540456112
Category : Science
Languages : en
Pages : 398
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Book Description
Every cell has developed mechanisms to respond to changes in its environment and to adapt its growth and metabolism to unfavorable conditions. The unicellular eukaryote yeast has long proven as a particularly useful model system for the analysis of cellular stress responses, and the completion of the yeast genome sequence has only added to its power This volume comprehensively reviews both the basic features of the yeast genral stress response and the specific adapations to different stress types (nutrient depletion, osmotic and heat shock as well as salt and oxidative stress). It includes the latest findings in the field and discusses the implications for the analysis of stress response mechanisms in higher eukaryotes as well.
Author: Lilia Alberghina
Publisher: Springer Science & Business Media
ISBN: 9783540742692
Category : Computers
Languages : en
Pages : 432
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Book Description
For life to be understood and disease to become manageable, the wealth of postgenomic data now needs to be made dynamic. This development requires systems biology, integrating computational models for cells and organisms in health and disease; quantitative experiments (high-throughput, genome-wide, living cell, in silico); and new concepts and principles concerning interactions. This book defines the new field of systems biology and discusses the most efficient experimental and computational strategies. The benefits for industry, such as the new network-based drug-target design validation, and testing, are also presented.
Author: Channing Der
Publisher: Springer
ISBN: 9781402043284
Category : Medical
Languages : en
Pages : 0
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Book Description
Since 1982, Ras proteins have been the subject of intense research investigation by the biomedical research community. The wide interest in Ras has been stimulated for three key reasons. This book features chapters contributed by leading investigators in the field that highlight the current state-of-the art in Ras biochemistry, structure and biology. This book is an excellent reference for students in the biomedical sciences and for investigators in the field.
Author: Terry Wood
Publisher: Elsevier
ISBN: 0323160018
Category : Science
Languages : en
Pages : 217
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Book Description
The Pentose Phosphate Pathway aims to explore the pentose phosphate cycle and the practical techniques applied in its investigation. The main focus of the book is the pentose phosphate cycle in animals as well as microorganisms, and does not discuss the one related to photosynthesis. The book covers the formulation of the pathway, its types, and its alternative formulations; the preparation, processes, and analysis of the pathway; and the enzymes involved. Also covered in the book are the intermediates in intact cells and tissues; distribution of enzymes among different tissues and species; the operation, regulation, and overall control of the pathway; and the clinical, nutritional, and metabolic aspects of the pathway. The text is recommended for biologists and biochemists who would like to understand further the pentose phosphate pathway and the processes related to it.
Author: Richard E. Kendrick
Publisher: Springer Science & Business Media
ISBN: 9780792325505
Category : Science
Languages : en
Pages : 868
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Book Description
David Dickinson is a household name, the king of the catchphrase, undisputed darling of daytime TV and a rising star. He's a respected antiques expert and exudes a taste for the finer things in life. But the road to his success has not been as smooth as his patter and he's learnt a lot at the school of hard knocks.
Author: Maryam Sarwat
Publisher: Springer
ISBN: 3319421832
Category : Science
Languages : en
Pages : 355
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Book Description
This two-volume set takes an in-depth look at stress signaling in plants from a uniquely genomic and proteomic perspective and offers a comprehensive treatise that covers all of the signaling pathways and mechanisms that have been researched so far. Currently, plant diseases, extreme weather caused by climate change, drought and an increase in metals in soil are amongst the major limiting factors of crop production worldwide. They devastate not only the food supply but also the economy of a nation. With global food scarcity in mind, there is an urgent need to develop crop plants with increased stress tolerance so as to meet the global food demands and to preserve the quality of our planet. In order to do this, it is necessary to understand how plants react and adapt to stress from the genomic and proteomic perspective. Plants adapt to stress conditions by activating cascades of molecular mechanisms, which result in alterations in gene expression and synthesis of protective proteins. From the perception of the stimulus to the transduction of the signal, followed by an appropriate cellular response, the plants employ a complex network of primary and secondary messenger molecules. Cells exercise a large number of noticeably distinct signaling pathways to regulate their activity. In order to contend with different environmental adversities, plants have developed a series of mechanisms at the physiological, cellular and molecular levels that respond to stress. Each chapter in this volume provides an in-depth explanation of what we currently know of a particular aspect of stress signaling and where we are heading. Together with the highly successful first volume, Stress Signaling in Plants: Genomics and Proteomics Perspective, Volume 2 covers an important aspect of plant biology for both students and seasoned researchers.
Author: Peter Csermely
Publisher: Springer Science & Business Media
ISBN: 0387399755
Category : Science
Languages : en
Pages : 218
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Book Description
This book makes a novel synthesis of the molecular aspects of the stress response and long term adaptation processes with the system biology approach of biological networks. Authored by an exciting mixture of top experts and young rising stars, it provides a comprehensive summary of the field and identifies future trends.
Author: František Baluška
Publisher: Springer Science & Business Media
ISBN: 3540892281
Category : Science
Languages : en
Pages : 307
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Book Description
This is the first comprehensive monograph on all emerging topics in plant signaling. The book addresses diverse aspects of signaling at all levels of plant organization. Emphasis is placed on the integrative aspects of signaling.
