Publications by authors named "Amir Feizi"

19 Publications

  • Page 1 of 1

Human brown adipose tissue is phenocopied by classical brown adipose tissue in physiologically humanized mice.

Nat Metab 2019 08 19;1(8):830-843. Epub 2019 Aug 19.

Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.

Human and rodent brown adipose tissues (BAT) appear morphologically and molecularly different. Here we compare human BAT with both classical brown and brite/beige adipose tissues of 'physiologically humanized' mice: middle-aged mice living under conditions approaching human thermal and nutritional conditions, that is, prolonged exposure to thermoneutral temperature (approximately 30 °C) and to an energy-rich (high-fat, high-sugar) diet. We find that the morphological, cellular and molecular characteristics (both marker and adipose-selective gene expression) of classical brown fat, but not of brite/beige fat, of these physiologically humanized mice are notably similar to human BAT. We also demonstrate, both in silico and experimentally, that in physiologically humanized mice only classical BAT possesses a high thermogenic potential. These observations suggest that classical rodent BAT is the tissue of choice for translational studies aimed at recruiting human BAT to counteract the development of obesity and its comorbidities.
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http://dx.doi.org/10.1038/s42255-019-0101-4DOI Listing
August 2019

Human thermogenic adipocyte regulation by the long noncoding RNA LINC00473.

Nat Metab 2020 05 21;2(5):397-412. Epub 2020 May 21.

The Centre of Inflammation and Metabolism and the Centre for Physical Activity Research, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.

Human thermogenic adipose tissue mitigates metabolic disease, raising much interest in understanding its development and function. Here, we show that human thermogenic adipocytes specifically express a primate-specific long non-coding RNA, which is highly correlated with UCP1 expression and decreased in obesity and type-2 diabetes. is detected in progenitor cells, and increases upon differentiation and in response to cAMP. In contrast to other known adipocyte LincRNAs, LINC00473 shuttles out of the nucleus, colocalizes and can be crosslinked to mitochondrial and lipid droplet proteins. Up- or down- regulation of results in reciprocal alterations in lipolysis, respiration and transcription of genes associated with mitochondrial oxidative metabolism. Depletion of PLIN1 results in impaired cAMP-responsive expression and lipolysis, indicating bidirectional interactions between PLIN1, LINC00473 and mitochondrial oxidative functions. Thus, we suggest that is a key regulator of human thermogenic adipocyte function, and reveals a role for a LincRNA in inter-organelle communication and human energy metabolism.
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http://dx.doi.org/10.1038/s42255-020-0205-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7241442PMC
May 2020

Genome-scale reconstructions of the mammalian secretory pathway predict metabolic costs and limitations of protein secretion.

Nat Commun 2020 01 2;11(1):68. Epub 2020 Jan 2.

Department of Bioengineering, University of California, San Diego, La Jolla, CA, 92093, USA.

In mammalian cells, >25% of synthesized proteins are exported through the secretory pathway. The pathway complexity, however, obfuscates its impact on the secretion of different proteins. Unraveling its impact on diverse proteins is particularly important for biopharmaceutical production. Here we delineate the core secretory pathway functions and integrate them with genome-scale metabolic reconstructions of human, mouse, and Chinese hamster ovary cells. The resulting reconstructions enable the computation of energetic costs and machinery demands of each secreted protein. By integrating additional omics data, we find that highly secretory cells have adapted to reduce expression and secretion of other expensive host cell proteins. Furthermore, we predict metabolic costs and maximum productivities of biotherapeutic proteins and identify protein features that most significantly impact protein secretion. Finally, the model successfully predicts the increase in secretion of a monoclonal antibody after silencing a highly expressed selection marker. This work represents a knowledgebase of the mammalian secretory pathway that serves as a novel tool for systems biotechnology.
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http://dx.doi.org/10.1038/s41467-019-13867-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6940358PMC
January 2020

Heterogeneity in the perirenal region of humans suggests presence of dormant brown adipose tissue that contains brown fat precursor cells.

Mol Metab 2019 06 15;24:30-43. Epub 2019 Mar 15.

The Centre of Inflammation and Metabolism and Centre for Physical Activity Research Rigshospitalet, University Hospital of Copenhagen, 2100, Denmark; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark. Electronic address:

Objective: Increasing the amounts of functionally competent brown adipose tissue (BAT) in adult humans has the potential to restore dysfunctional metabolism and counteract obesity. In this study, we aimed to characterize the human perirenal fat depot, and we hypothesized that there would be regional, within-depot differences in the adipose signature depending on local sympathetic activity.

Methods: We characterized fat specimens from four different perirenal regions of adult kidney donors, through a combination of qPCR mapping, immunohistochemical staining, RNA-sequencing, and pre-adipocyte isolation. Candidate gene signatures, separated by adipocyte morphology, were recapitulated in a murine model of unilocular brown fat induced by thermoneutrality and high fat diet.

Results: We identified widespread amounts of dormant brown adipose tissue throughout the perirenal depot, which was contrasted by multilocular BAT, primarily found near the adrenal gland. Dormant BAT was characterized by a unilocular morphology and a distinct gene expression profile, which partly overlapped with that of subcutaneous white adipose tissue (WAT). Brown fat precursor cells, which differentiated into functional brown adipocytes were present in the entire perirenal fat depot, regardless of state. We identified SPARC as a candidate adipokine contributing to a dormant BAT state, and CLSTN3 as a novel marker for multilocular BAT.

Conclusions: We propose that perirenal adipose tissue in adult humans consists mainly of dormant BAT and provide a data set for future research on factors which can reactivate dormant BAT into active BAT, a potential strategy for combatting obesity and metabolic disease.
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http://dx.doi.org/10.1016/j.molmet.2019.03.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6531810PMC
June 2019

A Systematic Investigation of the Malignant Functions and Diagnostic Potential of the Cancer Secretome.

Cell Rep 2019 03;26(10):2622-2635.e5

Department of Biology and Biological Engineering, Chalmers University of Technology, Kemivägen 10, Gothenburg, Sweden; Wallenberg Centre for Protein Research, Chalmers University of Technology, Kemivägen 10, Gothenburg, Sweden; Science for Life Laboratory, KTH Royal Institute of Technology, Stockholm, Sweden; Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, 2800 Kgs. Lyngby, Denmark. Electronic address:

The collection of proteins secreted from a cell-the secretome-is of particular interest in cancer pathophysiology due to its diagnostic potential and role in tumorigenesis. However, cancer secretome studies are often limited to one tissue or cancer type or focus on biomarker prediction without exploring the associated functions. We therefore conducted a pan-cancer analysis of secretome gene expression changes to identify candidate diagnostic biomarkers and to investigate the underlying biological function of these changes. Using transcriptomic data spanning 32 cancer types and 30 healthy tissues, we quantified the relative diagnostic potential of secretome proteins for each cancer. Furthermore, we offer a potential mechanism by which cancer cells relieve secretory pathway stress by decreasing the expression of tissue-specific genes, thereby facilitating the secretion of proteins promoting invasion and proliferation. These results provide a more systematic understanding of the cancer secretome, facilitating its use in diagnostics and its targeting for therapeutic development.
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http://dx.doi.org/10.1016/j.celrep.2019.02.025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6441842PMC
March 2019

Human protein secretory pathway genes are expressed in a tissue-specific pattern to match processing demands of the secretome.

NPJ Syst Biol Appl 2017 18;3:22. Epub 2017 Aug 18.

Department of Biology and Biological Engineering, Kemivägen 10, Chalmers University of Technology, SE41296 Gothenburg, Sweden.

Protein secretory pathway in eukaryal cells is responsible for delivering functional secretory proteins. The dysfunction of this pathway causes a range of important human diseases from congenital disorders to cancer. Despite the piled-up knowledge on the molecular biology and biochemistry level, the tissue-specific expression of the secretory pathway genes has not been analyzed on the transcriptome level. Based on the recent RNA-sequencing studies, the largest fraction of tissue-specific transcriptome encodes for the secretome (secretory proteins). Here, the question arises that if the expression levels of the secretory pathway genes have a tissue-specific tuning. In this study, we tackled this question by performing a meta-analysis of the recently published transcriptome data on human tissues. As a result, we detected 68 as called "extreme genes" which show an unusual expression pattern in specific gene families of the secretory pathway. We also inspected the potential functional link between detected extreme genes and the corresponding tissues enriched secretome. As a result, the detected extreme genes showed correlation with the enrichment of the nature and number of specific post-translational modifications in each tissue's secretome. Our findings conciliate both the housekeeping and tissue-specific nature of the protein secretory pathway, which we attribute to a fine-tuned regulation of defined gene families to support the diversity of secreted proteins and their modifications.
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http://dx.doi.org/10.1038/s41540-017-0021-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5562915PMC
August 2017

Autophagy induction regulates influenza virus replication in a time-dependent manner.

J Med Microbiol 2017 Apr;66(4):536-541

Department of Hepatitis and AIDS, Pasteur Institute of Iran, Tehran, Iran.

Purpose: Autophagy plays a key role in host defence responses against microbial infections by promoting degradation of pathogens and participating in acquired immunity. The interaction between autophagy and viruses is complex, and this pathway is hijacked by several viruses. Influenza virus (IV) interferes with autophagy through its replication and increases the accumulation of autophagosomes by blocking lysosome fusion. Thus, autophagy could be an effective area for antiviral research.

Methodology: In this study, we evaluated the effect of autophagy on IV replication. Two cell lines were transfected with Beclin-1 expression plasmid before (prophylactic approach) and after (therapeutic approach) IV inoculation.Results/Key findings. Beclin-1 overexpression in the cells infected by virus induced autophagy to 26 %. The log10haemagglutinin titre and TCID50 (tissue culture infective dose giving 50 % infection) of replicating virus were measured at 24 and 48 h post-infection. In the prophylactic approach, the virus titre was enhanced significantly at 24 h post-infection (P≤0.01), but it was not significantly different from the control at 48 h post-infection. In contrast, the therapeutic approach of autophagy induction inhibited the virus replication at 24 and 48 h post-infection. Additionally, we showed that inhibition of autophagy using 3-methyladenine reduced viral replication.

Conclusion: This study revealed that the virus (H1N1) titre was controlled in a time-dependent manner following autophagy induction in host cells. Manipulation of autophagy during the IV life cycle can be targeted both for antiviral aims and for increasing viral yield for virus production.
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http://dx.doi.org/10.1099/jmm.0.000455DOI Listing
April 2017

Early vs Late Coronary Angiography and Intervention Following Thrombolytic Therapy; a Cohort Study.

Emerg (Tehran) 2017 11;5(1):e32. Epub 2017 Jan 11.

Clinical Research Development Center, Bouali Hospital, Islamic Azad University, Tehran Medical Sciences Branch, Tehran, Iran.

Introduction: The precise time of using percutaneous coronary intervention (PCI) after fibrinolytic therapy for maximum efficiency and minimum side effects is still undetermined. Therefore, the present study was designed to compare the outcome of myocardial infarction (MI) patients who underwent surgical intervention (angiography and PCI) within 48 hours of thrombolytic therapy or after that.

Methods: The present study is a prospective cohort study aiming to compare the occurrence of no-reflow phenomenon, unstable angina, bleeding during intervention, and one month major adverse cardiac outcomes (recurrent MI, need for repeating surgical intervention, and mortality) between MI patents undergoing surgical intervention within the first 48 hours of or after 48 hours of thrombolytic therapy.

Results: 90 patients with the mean age of 54.97 ± 10.54 were studied (86.67% male). 50 (56%) patients underwent surgical intervention within 48 hours and 40 (44%) after that. The 2 groups were not significantly different regarding baseline characteristics. No-reflow phenomenon in the < 48 hours group was about twice the > 48 hours group (OR = 0.35; 95% confidence interval: 0.14 - 0.92; p = 0.03), other outcomes were not significantly different. No case of mortality was seen in the 1 month follow up.

Conclusion: Based on the results of the present study, it seems that no-reflow phenomenon rate is significantly lower in patients undergoing surgical intervention after 48 hours of fibrinolytic therapy. The difference between the two groups regarding prevalence of major adverse cardiac outcomes was not statistically significant.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5325902PMC
January 2017

Intravenous Amiodarone versus Digoxin in Atrial Fibrillation Rate Control; a Clinical Trial.

Emerg (Tehran) 2017 10;5(1):e29. Epub 2017 Jan 10.

Emergency Department, Bouali Hospital, Islamic Azad University, Tehran Medical Sciences Branch, Tehran, Iran.

Introduction: Treatment of rapid ventricular response arterial fibrillation (rapid AF) varies depending on the decision of the in-charge physician, condition of the patient, availability of the drug, and the treatment protocol of the hospital. The present study was designed aiming to compare IV digoxin and amiodarone in controlling the heart rate of patients presenting to emergency department with rapid AF and relative contraindication for first line drug in this regard.

Method: In the present clinical trial, patients presented to the ED with rapid AF and relative contraindication for calcium channel blockers and beta-blockers were treated with either IV amiodarone or IV digoxin and compared regarding success rate and complication using SPSS version 22. P < 0.05 was considered as statistically significant.

Results: 84 patients were randomly allocated to either amiodarone or digoxin treatment groups of 42 (53.6% male). The mean age of the studied patients was 61.8 ± 11.14 years (38 - 79). No significant difference was present regarding baseline characteristics. The rate of treatment failure was 21.4% (9 cases) in amiodarone and 59.5% (25 cases) in digoxin groups (p < 0.001). The mean onset of action was 56.66 ± 39.52 minutes (10 - 180) in amiodarone receivers and 135.38 ± 110.41 minutes (25 - 540) in digoxin group (p < 0.001). None of the patients showed any adverse outcomes of hypotension, bradycardia, and rhythm control.

Conclusion: Based on the findings of the present study, rapid AF patients with relative contraindication for calcium channel blockers or beta-blockers who had received amiodarone experienced both higher (about 2 times) treatment success and a more rapid (about 2.5 times) response compared to those who received IV digoxin.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5325898PMC
January 2017

Evolutionary engineering reveals divergent paths when yeast is adapted to different acidic environments.

Metab Eng 2017 01 2;39:19-28. Epub 2016 Nov 2.

Department of Biology and Biological Engineering, Chalmers University of Technology, Kemivägen 10, SE-412 96 Gothenburg, Sweden; Science for Life Laboratory, Royal Institute for Technology, SE-171 21 Stockholm, Sweden; Novo Nordisk Foundation Center for Biosustainability, Chalmers University of Technology, Kemivägen 10, SE-412 96 Gothenburg, Sweden; Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kemitorvet Bygning 220, DK-2820 Lyngby, Denmark. Electronic address:

Tolerance of yeast to acid stress is important for many industrial processes including organic acid production. Therefore, elucidating the molecular basis of long term adaptation to acidic environments will be beneficial for engineering production strains to thrive under such harsh conditions. Previous studies using gene expression analysis have suggested that both organic and inorganic acids display similar responses during short term exposure to acidic conditions. However, biological mechanisms that will lead to long term adaptation of yeast to acidic conditions remains unknown and whether these mechanisms will be similar for tolerance to both organic and inorganic acids is yet to be explored. We therefore evolved Saccharomyces cerevisiae to acquire tolerance to HCl (inorganic acid) and to 0.3M L-lactic acid (organic acid) at pH 2.8 and then isolated several low pH tolerant strains. Whole genome sequencing and RNA-seq analysis of the evolved strains revealed different sets of genome alterations suggesting a divergence in adaptation to these two acids. An altered sterol composition and impaired iron uptake contributed to HCl tolerance whereas the formation of a multicellular morphology and rapid lactate degradation was crucial for tolerance to high concentrations of lactic acid. Our findings highlight the contribution of both the selection pressure and nature of the acid as a driver for directing the evolutionary path towards tolerance to low pH. The choice of carbon source was also an important factor in the evolutionary process since cells evolved on two different carbon sources (raffinose and glucose) generated a different set of mutations in response to the presence of lactic acid. Therefore, different strategies are required for a rational design of low pH tolerant strains depending on the acid of interest.
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http://dx.doi.org/10.1016/j.ymben.2016.10.010DOI Listing
January 2017

Strategies to improve usability and preserve accuracy in biological sequence databases.

Proteomics 2016 09;16(18):2454-60

Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.

Biology is increasingly dependent on large-scale analysis, such as proteomics, creating a requirement for efficient bioinformatics. Bioinformatic predictions of biological functions rely upon correctly annotated database sequences, and the presence of inaccurately annotated or otherwise poorly described sequences introduces noise and bias to biological analyses. Accurate annotations are, for example, pivotal for correct identification of polypeptide fragments. However, standards for how sequence databases are organized and presented are currently insufficient. Here, we propose five strategies to address fundamental issues in the annotation of sequence databases: (i) to clearly separate experimentally verified and unverified sequence entries; (ii) to enable a system for tracing the origins of annotations; (iii) to separate entries with high-quality, informative annotation from less useful ones; (iv) to integrate automated quality-control software whenever such tools exist; and (v) to facilitate postsubmission editing of annotations and metadata associated with sequences. We believe that implementation of these strategies, for example as requirements for publication of database papers, would enable biology to better take advantage of large-scale data.
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http://dx.doi.org/10.1002/pmic.201600034DOI Listing
September 2016

RNA-seq analysis of Pichia anomala reveals important mechanisms required for survival at low pH.

Microb Cell Fact 2015 Sep 16;14:143. Epub 2015 Sep 16.

Department of Biology and Biological Engineering, Chalmers University of Technology, Kemivägen 10, 412 96, Gothenburg, Sweden.

Background: The product yield and titers of biological processes involving the conversion of biomass to desirable chemicals can be limited by environmental stresses encountered by the microbial hosts used for the bioconversion. One of these main stresses is growth inhibition due to exposure to low pH conditions. In order to circumvent this problem, understanding the biological mechanisms involved in acid stress response and tolerance is essential. Characterisation of wild yeasts that have a natural ability to resist such harsh conditions will pave the way to understand the biological basis underlying acid stress resistance. Pichia anomala possesses a unique ability to adapt to and tolerate a number of environmental stresses particularly low pH stress giving it the advantage to outcompete other microorganisms under such conditions. However, the genetic basis of this resistance has not been previously studied.

Results: To this end, we isolated an acid resistant strain of P. anomala, performed a gross phenotypic characterisation at low pH and also performed a whole genome and total RNA sequencing. By integrating the RNA-seq data with the genome sequencing data, we found that several genes associated with different biological processes including proton efflux, the electron transfer chain and oxidative phosphorylation were highly expressed in P. anomala cells grown in low pH media. We therefore present data supporting the notion that a high expression of proton pumps in the plasma membrane coupled with an increase in mitochondrial ATP production enables the high level of acid stress tolerance of P. anomala.

Conclusions: Our findings provide insight into the molecular and genetic basis of low pH tolerance in P. anomala which was previously unknown. Ultimately, this is a step towards developing non-conventional yeasts such as P. anomala for the production of industrially relevant chemicals under low pH conditions.
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http://dx.doi.org/10.1186/s12934-015-0331-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4574170PMC
September 2015

HCSD: the human cancer secretome database.

Database (Oxford) 2015 14;2015:bav051. Epub 2015 Jun 14.

Novo Nordisk Foundation Center for Biosustainability, Department of Biology and Biological Engineering, Chalmers University of Technology, SE-41296 Göteborg, Sweden, Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Fremtidsvej 3, DK-2970 Hørsholm, Denmark and Novozymes A/S, Krogshoejvej 36, 2880 Bagsvaerd, Denmark Novo Nordisk Foundation Center for Biosustainability, Department of Biology and Biological Engineering, Chalmers University of Technology, SE-41296 Göteborg, Sweden, Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Fremtidsvej 3, DK-2970 Hørsholm, Denmark and Novozymes A/S, Krogshoejvej 36, 2880 Bagsvaerd, Denmark Novo Nordisk Foundation Center for Biosustainability, Department of Biology and Biological Engineering, Chalmers University of Technology, SE-41296 Göteborg, Sweden, Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Fremtidsvej 3, DK-2970 Hørsholm, Denmark and Novozymes A/S, Krogshoejvej 36, 2880 Bagsvaerd, Denmark

The human cancer secretome database (HCSD) is a comprehensive database for human cancer secretome data. The cancer secretome describes proteins secreted by cancer cells and structuring information about the cancer secretome will enable further analysis of how this is related with tumor biology. The secreted proteins from cancer cells are believed to play a deterministic role in cancer progression and therefore may be the key to find novel therapeutic targets and biomarkers for many cancers. Consequently, huge data on cancer secretome have been generated in recent years and the lack of a coherent database is limiting the ability to query the increasing community knowledge. We therefore developed the Human Cancer Secretome Database (HCSD) to fulfil this gap. HCSD contains >80 000 measurements for about 7000 nonredundant human proteins collected from up to 35 high-throughput studies on 17 cancer types. It has a simple and user friendly query system for basic and advanced search based on gene name, cancer type and data type as the three main query options. The results are visualized in an explicit and interactive manner. An example of a result page includes annotations, cross references, cancer secretome data and secretory features for each identified protein.
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http://dx.doi.org/10.1093/database/bav051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4480035PMC
March 2016

Biofuels. Altered sterol composition renders yeast thermotolerant.

Science 2014 Oct 2;346(6205):75-8. Epub 2014 Oct 2.

Novo Nordisk Foundation Center for Biosustainability, Chalmers University of Technology, SE-41296 Gothenburg, Sweden. Department of Chemical and Biological Engineering, Chalmers Unversity of Technology, SE-41296 Gothenburg, Sweden. Novo Nordisk Foundation Center for Biosustainability, DK-2970 Hørsholm, Denmark.

Ethanol production for use as a biofuel is mainly achieved through simultaneous saccharification and fermentation by yeast. Operating at ≥40°C would be beneficial in terms of increasing efficiency of the process and reducing costs, but yeast does not grow efficiently at those temperatures. We used adaptive laboratory evolution to select yeast strains with improved growth and ethanol production at ≥40°C. Sequencing of the whole genome, genome-wide gene expression, and metabolic-flux analyses revealed a change in sterol composition, from ergosterol to fecosterol, caused by mutations in the C-5 sterol desaturase gene, and increased expression of genes involved in sterol biosynthesis. Additionally, large chromosome III rearrangements and mutations in genes associated with DNA damage and respiration were found, but contributed less to the thermotolerant phenotype.
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http://dx.doi.org/10.1126/science.1258137DOI Listing
October 2014

Genome-scale analysis of the high-efficient protein secretion system of Aspergillus oryzae.

BMC Syst Biol 2014 Jun 24;8:73. Epub 2014 Jun 24.

Novo Nordisk Foundation Center for Biosustainability, Department of Chemical and Biologicl Engineering, Chalmers University of Technology, SE-41296 Göteborg, Sweden.

Background: The koji mold, Aspergillus oryzae is widely used for the production of industrial enzymes due to its particularly high protein secretion capacity and ability to perform post-translational modifications. However, systemic analysis of its secretion system is lacking, generally due to the poorly annotated proteome.

Results: Here we defined a functional protein secretory component list of A. oryzae using a previously reported secretory model of S. cerevisiae as scaffold. Additional secretory components were obtained by blast search with the functional components reported in other closely related fungal species such as Aspergillus nidulans and Aspergillus niger. To evaluate the defined component list, we performed transcriptome analysis on three α-amylase over-producing strains with varying levels of secretion capacities. Specifically, secretory components involved in the ER-associated processes (including components involved in the regulation of transport between ER and Golgi) were significantly up-regulated, with many of them never been identified for A. oryzae before. Furthermore, we defined a complete list of the putative A. oryzae secretome and monitored how it was affected by overproducing amylase.

Conclusion: In combination with the transcriptome data, the most complete secretory component list and the putative secretome, we improved the systemic understanding of the secretory machinery of A. oryzae in response to high levels of protein secretion. The roles of many newly predicted secretory components were experimentally validated and the enriched component list provides a better platform for driving more mechanistic studies of the protein secretory pathway in this industrially important fungus.
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http://dx.doi.org/10.1186/1752-0509-8-73DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4086290PMC
June 2014

Metabolic and protein interaction sub-networks controlling the proliferation rate of cancer cells and their impact on patient survival.

Sci Rep 2013 Oct 24;3:3041. Epub 2013 Oct 24.

Department of Chemical and Biological Engineering, Kemivägen 10, Chalmers University of Technology, SE412 96 Gothenburg, Sweden.

Cancer cells can have a broad scope of proliferation rates. Here we aim to identify the molecular mechanisms that allow some cancer cell lines to grow up to 4 times faster than other cell lines. The correlation of gene expression profiles with the growth rate in 60 different cell lines has been analyzed using several genome-scale biological networks and new algorithms. New possible regulatory feedback loops have been suggested and the known roles of several cell cycle related transcription factors have been confirmed. Over 100 growth-correlated metabolic sub-networks have been identified, suggesting a key role of simultaneous lipid synthesis and degradation in the energy supply of the cancer cells growth. Many metabolic sub-networks involved in cell line proliferation appeared also to correlate negatively with the survival expectancy of colon cancer patients.
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http://dx.doi.org/10.1038/srep03041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3807112PMC
October 2013

Genome-scale modeling of the protein secretory machinery in yeast.

PLoS One 2013 7;8(5):e63284. Epub 2013 May 7.

Novo Nordisk Foundation Center for Biosustainability, Chalmers University of Technology, Gothenburg, Sweden.

The protein secretory machinery in Eukarya is involved in post-translational modification (PTMs) and sorting of the secretory and many transmembrane proteins. While the secretory machinery has been well-studied using classic reductionist approaches, a holistic view of its complex nature is lacking. Here, we present the first genome-scale model for the yeast secretory machinery which captures the knowledge generated through more than 50 years of research. The model is based on the concept of a Protein Specific Information Matrix (PSIM: characterized by seven PTMs features). An algorithm was developed which mimics secretory machinery and assigns each secretory protein to a particular secretory class that determines the set of PTMs and transport steps specific to each protein. Protein abundances were integrated with the model in order to gain system level estimation of the metabolic demands associated with the processing of each specific protein as well as a quantitative estimation of the activity of each component of the secretory machinery.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0063284PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3646752PMC
December 2013

Hybrid-controlled neurofuzzy networks analysis resulting in genetic regulatory networks reconstruction.

ISRN Bioinform 2012 1;2012:419419. Epub 2012 Nov 1.

Electrical and Computer Engineering Department, Ryerson University, Toronto, ON, Canada M5B 2K3.

Reverse engineering of gene regulatory networks (GRNs) is the process of estimating genetic interactions of a cellular system from gene expression data. In this paper, we propose a novel hybrid systematic algorithm based on neurofuzzy network for reconstructing GRNs from observational gene expression data when only a medium-small number of measurements are available. The approach uses fuzzy logic to transform gene expression values into qualitative descriptors that can be evaluated by using a set of defined rules. The algorithm uses neurofuzzy network to model genes effects on other genes followed by four stages of decision making to extract gene interactions. One of the main features of the proposed algorithm is that an optimal number of fuzzy rules can be easily and rapidly extracted without overparameterizing. Data analysis and simulation are conducted on microarray expression profiles of S. cerevisiae cell cycle and demonstrate that the proposed algorithm not only selects the patterns of the time series gene expression data accurately, but also provides models with better reconstruction accuracy when compared with four published algorithms: DBNs, VBEM, time delay ARACNE, and PF subjected to LASSO. The accuracy of the proposed approach is evaluated in terms of recall and F-score for the network reconstruction task.
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http://dx.doi.org/10.5402/2012/419419DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4393070PMC
May 2015