Article

Prospects of yeast systems biology for human health: integrating lipid, protein and energy metabolism.

Department of Chemical and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden.
FEMS Yeast Research (impact factor: 2.4). 09/2010; 10(8):1046-59. DOI:10.1111/j.1567-1364.2010.00689.x
Source: PubMed

ABSTRACT The yeast Saccharomyces cerevisiae is a widely used model organism for studying cell biology, metabolism, cell cycle and signal transduction. Many regulatory pathways are conserved between this yeast and humans, and it is therefore possible to study pathways that are involved in disease development in a model organism that is easy to manipulate and that allows for detailed molecular studies. Here, we briefly review pathways involved in lipid metabolism and its regulation, the regulatory network of general metabolic regulator Snf1 (and its human homologue AMPK) and the proteostasis network with its link to stress and cell death. All the mentioned pathways can be used as model systems for the study of homologous pathways in human cells and a failure in these pathways is directly linked to several human diseases such as the metabolic syndrome and neurodegeneration. We demonstrate how different yeast pathways are conserved in humans, and we discuss the possibilities of using the systems biology approach to study and compare the pathways of relevance with the objective to generate hypotheses and gain new insights.

0 0
 · 
0 Bookmarks
 · 
68 Views
  • Source
    Article: Imbalance of heterologous protein folding and disulfide bond formation rates yields runaway oxidative stress.
    Keith E J Tyo, Zihe Liu, Dina Petranovic, Jens Nielsen
    [show abstract] [hide abstract]
    ABSTRACT: The protein secretory pathway must process a wide assortment of native proteins for eukaryotic cells to function. As well, recombinant protein secretion is used extensively to produce many biologics and industrial enzymes. Therefore, secretory pathway dysfunction can be highly detrimental to the cell and can drastically inhibit product titers in biochemical production. Because the secretory pathway is a highly-integrated, multi-organelle system, dysfunction can happen at many levels and dissecting the root cause can be challenging. In this study, we apply a systems biology approach to analyze secretory pathway dysfunctions resulting from heterologous production of a small protein (insulin precursor) or a larger protein (α-amylase). HAC1-dependent and independent dysfunctions and cellular responses were apparent across multiple datasets. In particular, processes involving (a) degradation of protein/recycling amino acids, (b) overall transcription/translation repression, and (c) oxidative stress were broadly associated with secretory stress. Apparent runaway oxidative stress due to radical production observed here and elsewhere can be explained by a futile cycle of disulfide formation and breaking that consumes reduced glutathione and produces reactive oxygen species. The futile cycle is dominating when protein folding rates are low relative to disulfide bond formation rates. While not strictly conclusive with the present data, this insight does provide a molecular interpretation to an, until now, largely empirical understanding of optimizing heterologous protein secretion. This molecular insight has direct implications on engineering a broad range of recombinant proteins for secretion and provides potential hypotheses for the root causes of several secretory-associated diseases.
    BMC Biology 03/2012; 10:16. · 5.75 Impact Factor
  • Source
    Article: Systems biology: new institute and applications.
    Jieming Chen
    [show abstract] [hide abstract]
    ABSTRACT: The Yale Systems Biology Institute (YSBI) sponsored its first symposium at the university's West Campus in October 2010. The symposium served to provide Yale's scientific community with a glimpse into the wide range of research at the forefront of this interdisciplinary field. YSBI was conceived less than a year ago, and the event was the perfect forum for its debut, both at Yale and in the U.S. scientific community. This article includes a brief overview of the different topics presented at the symposium, followed by a discussion of the advantages and challenges of practical application of systems biology.
    The Yale journal of biology and medicine 03/2011; 84(1):59-61.
  • Source
    Article: Effects of abiotic stress on plants: a systems biology perspective.
    Grant R Cramer, Kaoru Urano, Serge Delrot, Mario Pezzotti, Kazuo Shinozaki
    [show abstract] [hide abstract]
    ABSTRACT: The natural environment for plants is composed of a complex set of abiotic stresses and biotic stresses. Plant responses to these stresses are equally complex. Systems biology approaches facilitate a multi-targeted approach by allowing one to identify regulatory hubs in complex networks. Systems biology takes the molecular parts (transcripts, proteins and metabolites) of an organism and attempts to fit them into functional networks or models designed to describe and predict the dynamic activities of that organism in different environments. In this review, research progress in plant responses to abiotic stresses is summarized from the physiological level to the molecular level. New insights obtained from the integration of omics datasets are highlighted. Gaps in our knowledge are identified, providing additional focus areas for crop improvement research in the future.
    BMC Plant Biology 11/2011; 11:163. · 3.45 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

cell biology
 
cell death
 
different yeast pathways
 
gain new insights
 
general metabolic regulator Snf1
 
homologous pathways
 
human cells
 
human diseases
 
human homologue AMPK
 
mentioned pathways
 
model systems
 
molecular studies
 
proteostasis network
 
regulatory network
 
regulatory pathways
 
signal transduction
 
study pathways
 
systems biology approach
 
used model organism
 
yeast Saccharomyces cerevisiae