Project description:diaPASEF proteomic analysis of KRASG12D mutant cell lines treated with MRTX1133. This dataset is part of a multiomic study featuring the metabolomics and single cell proteomics of 3,000 cells treated with drug. Files are broken into multiple repositories to simplify the deposition and reanalysis of these files.
Project description:Heinemann2005 - Genome-scale reconstruction
of Staphylococcus aureus (iMH551)
This model is described in the article:
In silico genome-scale
reconstruction and validation of the Staphylococcus aureus
metabolic network.
Heinemann M, Kümmel A,
Ruinatscha R, Panke S.
Biotechnol. Bioeng. 2005 Dec; 92(7):
850-864
Abstract:
A genome-scale metabolic model of the Gram-positive,
facultative anaerobic opportunistic pathogen Staphylococcus
aureus N315 was constructed based on current genomic data,
literature, and physiological information. The model comprises
774 metabolic processes representing approximately 23% of all
protein-coding regions. The model was extensively validated
against experimental observations and it correctly predicted
main physiological properties of the wild-type strain, such as
aerobic and anaerobic respiration and fermentation. Due to the
frequent involvement of S. aureus in hospital-acquired
bacterial infections combined with its increasing antibiotic
resistance, we also investigated the clinically relevant
phenotype of small colony variants and found that the model
predictions agreed with recent findings of proteome analyses.
This indicates that the model is useful in assisting future
experiments to elucidate the interrelationship of bacterial
metabolism and resistance. To help directing future studies for
novel chemotherapeutic targets, we conducted a large-scale in
silico gene deletion study that identified 158 essential
intracellular reactions. A more detailed analysis showed that
the biosynthesis of glycans and lipids is rather rigid with
respect to circumventing gene deletions, which should make
these areas particularly interesting for antibiotic
development. The combination of this stoichiometric model with
transcriptomic and proteomic data should allow a new quality in
the analysis of clinically relevant organisms and a more
rationalized system-level search for novel drug targets.
This model is hosted on
BioModels Database
and identified by:
MODEL1507180072.
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To the extent possible under law, all copyright and related or
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Project description:Proteome profiles of Vibrio natriegens used for genome-scale metabolic modeling (GSSM). Profiling was performed across cell cultures grown aerobically on minimal medium. Cultures profiles were acquired across a range of salinities.
Project description:Proteome profiles of Vibrio natriegens used for genome-scale metabolic modeling (GSMM). Profiling was performed across cell cultures grown aerobically on minimal medium. Cultures profiles were acquired across a range of salinities.
Project description:The calcitonin receptor (CTR) signaling axis has been implicated in growth regulation in Glioblastoma (GBM). This study examines the molecular and signaling effects of salmon calcitonin (sCT) treatment in GBM using proteomic, cellular, in vivo, and computational approaches. Reverse Phase Protein Array (RPPA) analysis was performed to assess changes in protein expression in glioma cells following sCT treatment and to identify signaling pathways associated with CTR activation. Complementary biochemical and functional assays were used to characterize CTR-mediated regulation of the Hippo pathway. CTR expression was found to be elevated in human and murine glioma stem-like cells in comparison to their differentiated counterparts, and intranasal sCT treatment lead to decrease in the GSC-initiated tumor growth in orthotopic mouse glioma model. In parallel, microsecond-scale all-atom molecular dynamics simulations were conducted to examine structural features of wild-type and patient-derived mutant CTR variants and their interactions with calcitonin and Gα subunits. Together, this work reveals mechanism of CT/CTR axis, therapeutic implications of sCT, and impact of structural alterations in patient-derived CTR variants in GBM.
Project description:Endoglin (EDG) is a cell surface protein with an important role in the establishment of neo-angiogenesis and vasculogenic mimicry. EDG is part of the transforming growth factor-β (TGF-β) family, acting as an important co-receptor. EDG is shed from the cell surface into the extracellular compartment by matrix metalloproteinase 14 (MMP14), in its soluble form (sEDG). Both transmembrane and soluble forms of EDG exert important signaling functions in the development of new blood vessels and tumour progression. To better understand the role of EDG in Ewing sarcoma (ES), a deadly neoplasm of late childhood and adolescence, we test the efficacy of OMTX703, an endoglin-targeting antibody-drug conjugate in ES8 xenograft. Having determined an optimal dose for OMTX703, an additional experiment was conducted to assess the mechanism(s) of OMTX703 action and its potential mechanism(s) of resistance following a 2-week exposure to OMTX703 at 0, 10, 30, and 60 mg/kg; 246 proteins were assessed by reverse-phase protein array (RPPA). Analysis of variance (ANOVA), Pearson’s correlation as distance metric and Ward’s linkage as the clustering method using a false discovery rate (FDR) of 0.01, identified 60 proteins that discriminated between treatment groups (Matrix#1-Normalized Values). To investigate the proteomic changes associated with the heightened clinical activity of the 60 mg/kg dose, a secondary analysis was performed, which grouped the 10 mg/kg OMTX703 samples and the 10 mg/kg OMTX003 ones with the placebo-treated samples (Matrix#2-Normalized Values). Using a FDR of 0.0001, an absolute log2 fold change of 1.5, Pearson’s correlation as distance metric and Ward’s linkage as the clustering method, 22 proteins were discriminately identified between the 3 treatment groups (Matrix#2-Normalized Values). Notably, a protein regulator of altered metabolism (RPS6) was exclusively upregulated following OMTX703 (60mg/kg), and a second metabolism biomarker (LDHA) was down-expressed in the 30 and 60 mg/kg-treated groups. Conversely, BRD4 was one of about a dozen proteins that were preferentially down-regulated in samples treated only by 60 mg/kg.
Project description:Therapeutic neo-vasculogenesis in vivo can be achieved by the co-transplantation of human endothelial colony-forming progenitor cells (ECFCs) with mesenchymal stem/progenitor cells (MSPCs).The underlying mechanism is not completely understood thus hampering the development of novel stem cell therapies.We hypothesized that proteomic profiling could be used to retrieve the in vivo signaling signature during the initial phase of human neo-vasculogenesis. ECFCs and MSPCs were therefore either transplanted alone or co-transplanted subcutaneously into immune deficient mice. Early cell signaling, occurring within the first 24 hours in vivo, was analyzed using antibody microarray proteomic profiling.Vessel formation and persistence were verified in parallel transplants for up to 24 weeks. Proteomic analysis revealed significant alteration of regulatory components including caspases, calcium/calmodulin-dependent protein kinase, DNA protein kinase,human ErbB2 receptor-tyrosine kinase as well as mitogen-activated protein kinases.Therapeutic candidate caspase-4 was selected from array results for targeting vascular network formation in vitro as well as modulating therapeutic vasculogenesis in vivo. As a proof-of-principle, caspase-4 and general caspase-blocking led to diminished endothelial network formation in vitro and significantly decreased vasculogenesis in vivo. Proteomic profiling ex vivo thus unraveled a signaling signature which can be targeted to modulate neo-vasculogenesis in vivo.
Project description:<p>The goal of this project is to determine the genetic etiology of congenital arhinia and Bosma arhinia microphthalmia syndrome through a combination of whole-exome, whole-genome, and targeted sequencing followed by in silico, in vitro, and in vivo functional modeling. </p>