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Lactic Acid as an Epigenetic Metabolite in Glioblastoma

ABSTRACT: Lactic Acid as an Epigenetic Metabolite in Glioblastoma

PROVIDER: PRJNA607971 | ENA |

REPOSITORIES: ENA

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Lactic Acid as an Epigenetic Metabolite in Glioblastoma

Project description:Lactic Acid as an Epigenetic Metabolite in Glioblastoma

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Project description:We investigate the role of lactic acid in GBM cells as an epigenetic metabolite in the regulation of pro-survival gene expression.

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Lactic Acid as an Epigenetic Metabolite in Glioblastoma [ChIP-Seq]

Project description:Glioblastoma is the most common primary malignant brain tumor with an unfavorable prognosis and a reprogrammed metabolism. In order to define the role of lactic acid in the context of glioblastoma epigenetic remodeling, pediatric GBM cells, KNS42, were growth for 24h in different media conditions (starvation media -0.5mM Glucose; 0.5mM Glutamate or physiological media -5mM Glucose; 0mM Glutamate) with or without L-lactic acid for 24h. Thereafter, cells were harvested and samples were subjected to ChIP isolation using H3K27ac and H3K9ac antibodies. DNA was subsequently processed for CHIP sequencing to assess epigenetic changes mediated by lactic acid.

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Lactic Acid as an Epigenetic Metabolite in Glioblastoma

Project description:This SuperSeries is composed of the SubSeries listed below.

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Real-time quantitative PCR analysis of human peripheral blood mononuclear cells (PBMCs) treated with a metabolite from the human periapical granulomas.

Project description:Recently, L-lactic acid was identified as a unique metabolite in periapical granulomas. However, the biological roles of this metabolite in this lesion were unknown. Therefore, we aimed to investigate the inflammatory effect of L-lactic acid on peripheral blood mononuclear cells (PBMCs).

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Conferring Flocculation Phenotype to Pichia pastoris Improves D-lactic Acid Production and Tolerance

Project description:D-lactic acid is a three-carbon organic acid with a chiral structure and can improve the thermostability of polylactic acid. Microorganisms such as the methylotrophic yeast Pichia pastoris, which lack the natural ability to produce or accumulate high amounts of D-lactic acid, have been engineered to produce it in high titers. However, tolerance to D-lactic acid remains a challenge. In this study, we demonstrate that cell flocculation improves tolerance to D-lactic acid and leads to increased D-lactic acid production in Pichia pastoris. By incorporating a flocculation gene from Saccharomyces cerevisiae (ScFLO1) into P. pastoris KM71, we created a strain (KM71-ScFlo1) that demonstrated up to a 1.6-fold improvement in specific growth rate at high D-lactic acid concentrations. Furthermore, integrating a D-lactate dehydrogenase gene from Leuconostoc pseudomesenteroides (LpDLDH) into KM71-ScFlo1 resulted in an engineered strain (KM71-ScFlo1-LpDLDH) that can produce D-lactic acid at a titer of 5.12  0.35 g/L in 48 hours , a 2.6-fold improvement over the control strain lacking ScFLO1 expression. Transcriptomics analysis of this strain provided insights into the mechanism of increased tolerance to D-lactic acid including the upregulations of genes involved in lactate transport and iron metabolism. Overall, our work represents an advancement in the efficient microbial production of D-lactic acid by manipulating yeast flocculation.

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