Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Suppressors of amyloid-beta toxicity improve recombinant protein production by reducing oxidative stress and tunning cellular metabolism

ABSTRACT: In this study, we used a yeast Alzheimer’s disease model in which amyloid-β peptides (Aβ42) accumulate and induce stress-related phenotypes similar to overexpression of recombinant proteins. We validated that suppressors of Aβ42 cytotoxicity could reduce cell stress and improve recombinant protein production. Omics analyses and reverse metabolic engineering reveal potential regulatory hubs in cellular metabolism and protein synthesis, which may provide guidelines for engineering other cell factories for efficient protein production.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Saccharomyces Cerevisiae (baker's Yeast)

SUBMITTER: Egor Vorontsov

LAB HEAD: Martin Engqvist

PROVIDER: PXD030111 | Pride | 2022-05-12

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Publications

Suppressors of amyloid-β toxicity improve recombinant protein production in yeast by reducing oxidative stress and tuning cellular metabolism.

Chen Xin X Li Xiaowei X Ji Boyang B Wang Yanyan Y Ishchuk Olena P OP Vorontsov Egor E Petranovic Dina D Siewers Verena V Engqvist Martin K M MKM

Metabolic engineering 20220501

High-level production of recombinant proteins in industrial microorganisms is often limited by the formation of misfolded proteins or protein aggregates, which consequently induce cellular stress responses. We hypothesized that in a yeast Alzheimer's disease (AD) model overexpression of amyloid-β peptides (Aβ42), one of the main peptides relevant for AD pathologies, induces similar phenotypes of cellular stress. Using this humanized AD model, we previously identified suppressors of Aβ42 cytotoxi ...[more]

PMID: 35508267

Similar Datasets

Adaptations in metabolism and protein translation give rise to the Crabtree effect in yeast

Project description:We have studied Schizosaccharomyces pombe, Saccharomyces cerevisiae, Scheffersomyces (Pichia) stipites, and Kluyveromyces marxianus yeast using the modified IBAQ label-free method with the spiked universal protein standard (UPS2). Each species had been prepared in 3 culturing replicates, and the similarity of the replicates was assessed using the TMT relative quantification methodology.

2021-11-29 | PXD026313 | Pride

Loss of RET promotes mesenchymal identity in neuroblastoma cells

Project description:Aberrant activation of Anaplastic Lymphoma Kinase (ALK) drives neuroblastoma (NB). Previous work has identified the RET receptor tyrosine kinase (RTK) as a downstream target of ALK activity in NB models. We show here that ALK activation in response to ALKAL2 ligand results in the rapid phosphorylation of RET in NB cells, providing additional insight into the contribution of RET to the ALK driven gene signature in NB. To further address the role of RET in NB, RET knock-out (KO) SK-N-AS cells were generated by CRISPR/Cas9 genome engineering. Gene expression analysis of RET KO NB cells identified a reprogramming of NB cells to a mesenchymal (MES) phenotype that was characterized by increased migration and upregulation of the AXL and MET RTKs as well as integrins and extracellular matrix components. Strikingly, the upregulation of AXL in the absence of RET reflects the development timeline observed in the neural crest as progenitor cells undergo differentiation during embryonic development. Together, these findings suggest that a MES phenotype is promoted in mesenchymal NB cells in the absence of RET, reflective of a less differentiated developmental status.

2021-09-10 | PXD024551 | Pride

Impact of Age and Sex on Plasma Proteome Changes in Mice upon Radiation Exposure

Project description:The aim of this project is to assess the impact that age and sex have as parameters for biomarker discovery in radiation research using high-throughput proteomics.

2022-05-10 | PXD015859 | Pride

Expression data from Saccharomyces cerevisiae to evaluate the impact of suppressors of Aβ42 cytotoxicity on recombinant protein production

Project description:High-level production of pharmaceutical proteins in industrial microorganism is often limited due to the increased cellular stress from misfolded proteins or protein aggregates. Here, we explore the feasibility of applying a yeast Alzheimer’s disease (AD) model with accumulation of amyloid-β peptides (Aβ42), which presents similar phenotypes of cellular stress. We utilize the suppressors of Aβ42 cytotoxicity as potential metabolic engineering targets to improve industrial protein production. The transcriptomics analyses provide new insights towards developing synthetic yeast cell factories for biosynthesis of valuable pharmaceutical proteins.

2022-05-16 | GSE185570 | GEO

Quantifying gene expression control by growth and metabolism reveals distinct regulation of central carbon metabolism genes in yeast

Project description:Here we quantitatively describe the influence of cell growth rate and amino acid metabolic context on gene expression in the eukaryal model organism Saccharomyces cerevisiae. We show that growth rate and metabolic cues regulate ~70% of the yeast transcriptome and proteome, thereby exerting gene expression control in a global manner. We find that the growth rate-dependent differential gene expression largely reflects changing availabilities of the mRNA and protein synthesis machineries, while metabolic cues influences gene expression through the availabilities of amino acids and nucleotides. Genes in central carbon metabolism, however, are regulated independently of these global physiological controls, demonstrating distinct mechanisms to control their expression levels.

2021-03-15 | PXD021218 | Pride

TMT and Label-Free Quantification of Yeast Mitochondrial and Cellular Proteome During Different Stages of Growth

Project description:Tandem mass tag (TMT)-based relative quantification was used in combination with the intensity-based absolute quantity estimation (IBAQ) to study of both yeast cells and isolated yeast mitochondria during fermentative growth, diauxic shift, respiratory growth.

2020-03-06 | PXD012802 | Pride

ATR inhibition enables complete tumour regression in ALK-driven NB mouse models

Project description:High-risk neuroblastoma (NB) often involves amplification of the neural MYC (MYCN) oncogene as well as mutations in ALK. Currently, high-risk NB presents significant clinical challenges, and additional therapeutic options are needed. Oncogenes such as MYCN and ALK result in increased replication stress in cancer cells, offering one such therapeutically exploitable option. Here, we followed up on earlier phosphoproteomic analyses that identified ATR activity in ALK-driven NB cell lines. We tested several ATR inhibitors, identifying BAY 1895344 as the most potent inhibitor of NB cell growth and proliferation. Using RNA-Seq, proteomics and phosphoproteomics we characterized the response of NB cells and tumours to ATR inhibition, identifying key components of the DNA damage response (DDR) as well as ATRX, MYCN, E2F and DCK among other ATR targets in NB cells. ATR inhibition with BAY 1895344 also produced robust responses in mouse NB models. Remarkably, a 2 week protocol combining ATR and ALK inhibition led to complete regression of NB tumours in two independent NB genetically modified mouse tumour models. These results suggest that NB patients, particularly in high-risk groups with oncogene induced replication stress, may benefit from inhibition of ATR as therapeutic intervention.

2021-11-02 | PXD027187 | Pride

Proteome Changes in the Development of Chronic Human Papillomavirus Infection in Rwandan Women

Project description:What happens to the proteome when a high risk (HR)-HPV infection occurs, when it is cleared and when it becomes chronic was investigated.

2022-02-17 | PXD029798 | Pride

Immunological Sexual Dimorphism in Placenta and Its Response to Benzene Exposure

Project description:There is increasing concern regarding the adverse effects of air pollution on human health, and benzene is a major toxic compound in air pollution. Maternal benzene exposure has been associated with reproductive complications, such as preterm birth, low birth weight, and immunological and neurological complications in the offspring. However, it is poorly understood how benzene induces these complications. Our objective was to establish a full body inhalation mouse model for maternal benzene exposure that mimics clinical phenotypes observed in human populations, and characterize the maternal immune activation and placental response in our model. Here, we report that maternal immune activation triggered by benzene exposure during pregnancy leads to increased resorptions, abnormal placenta development and low birth weight of fetus. More importantly, there is a sexual dimorphic response to benzene exposure in female and male placentas. In the male placenta, the transcriptome changes reveal a more immunologically relevant profile, while females have a metabolically related profile. Furthermore, we discover the sexual dimorphic response could be a consequence of the sexual dimorphism of placenta at baseline, which indicates the significant difference between sexes in terms of the immunological processes in the placenta, both in human and mouse. Therefore, our findings established a benzene exposure mouse model and indicated the sexual dimorphism of placenta, which provides valuable reference for the future pregnancy studies.

2023-07-20 | PXD035085 | Pride

Measuring ageing-dependent transcriptional responses to human Aβ42 peptide in Drosophila brain

Project description:We have shown previously that older flies are intrinsically more susceptible to Aβ42 toxicity. Building upon these findings, this study aimed to determine the mechanisms by which ageing increases this vulnerability to damage in the brain. A fixed dose of Aβ42 peptide was induced in young (5d) versus older (20d) fly neurons, and then gene and protein expression changes examined in dissected fly brains using microarray analyses. This unbiased approach has revealed genes and pathways that correlate with increased susceptibility of the ageing brain to proteotoxicity.

2021-04-07 | E-MTAB-8865 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data