Project description:Glioblastoma patient samples were microdissected into ~20mg pieces and put onto a novel perfusion device, within an hour of resection. Samples were left for 8 days, at a flow rate of 3ul/min, with a media change at day 4. Treatment was with 1uM GSK3368715. Please refer to Barry et al. Lab-on-chip 2023 for details.
Project description:Perturbed proteostasis and mitochondrial dysfunction are often associated with age-related diseases such as Alzheimer’s and Parkinson’s diseases. However, the link between them remains incompletely understood. Mitochondrial dysfunction causes proteostasis imbalance, and cells respond to restore proteostasis by increasing proteasome activity and molecular chaperons in yeast and C. elegans. Here, we demonstrate the presence of similar responses in humans. Mitochondrial dysfunction upregulates a small heat shock protein HSPB1 and an immunoproteasome subunit PSMB9 leading to an increase in proteasome activity. HSPB1 and PSMB9 are required to prevent protein aggregation upon mitochondrial dysfunction. Moreover, PSMB9 expression is dependent on a translation elongation factor EEF1A2, and PSMB9-containing proteasomes are located near mitochondria, enabling fast local degradation of aberrant proteins. Our findings put a step forward in understanding the stress response triggered by mitochondrial dysfunction, and may be useful for therapeutic strategies to prevent or delay the onset of age-related diseases and attenuate their progression.
Project description:Perturbed proteostasis and mitochondrial dysfunction are often associated with age-related diseases such as Alzheimer’s and Parkinson’s diseases. However, the link between them remains incompletely understood. Mitochondrial dysfunction causes proteostasis imbalance, and cells respond to restore proteostasis by increasing proteasome activity and molecular chaperons in yeast and C. elegans. Here, we demonstrate the presence of similar responses in humans. Mitochondrial dysfunction upregulates a small heat shock protein HSPB1 and an immunoproteasome subunit PSMB9 leading to an increase in proteasome activity. HSPB1 and PSMB9 are required to prevent protein aggregation upon mitochondrial dysfunction. Moreover, PSMB9 expression is dependent on a translation elongation factor EEF1A2, and PSMB9-containing proteasomes are located near mitochondria, enabling fast local degradation of aberrant proteins. Our findings put a step forward in understanding the stress response triggered by mitochondrial dysfunction, and may be useful for therapeutic strategies to prevent or delay the onset of age-related diseases and attenuate their progression.
Project description:Perturbed proteostasis and mitochondrial dysfunction are often associated with age-related diseases such as Alzheimer’s and Parkinson’s diseases. However, the link between them remains incompletely understood. Mitochondrial dysfunction causes proteostasis imbalance, and cells respond to restore proteostasis by increasing proteasome activity and molecular chaperons in yeast and C. elegans. Here, we demonstrate the presence of similar responses in humans. Mitochondrial dysfunction upregulates a small heat shock protein HSPB1 and an immunoproteasome subunit PSMB9 leading to an increase in proteasome activity. HSPB1 and PSMB9 are required to prevent protein aggregation upon mitochondrial dysfunction. Moreover, PSMB9 expression is dependent on a translation elongation factor EEF1A2, and PSMB9-containing proteasomes are located near mitochondria, enabling fast local degradation of aberrant proteins. Our findings put a step forward in understanding the stress response triggered by mitochondrial dysfunction, and may be useful for therapeutic strategies to prevent or delay the onset of age-related diseases and attenuate their progression.
Project description:We use high through put RNA sequenceing technology to study the genome-wide expression profile of a unknown-function gene PG0686 mutant, designated as FLL361, in key-stone oral pathogen Porphyromonas gingivalis under anaerobic conditions and oxidative stress conditions.
Project description:We use high through put RNA sequenceing technology to study the genome-wide expression profile in an oral pathogen Filifactor alocis when co-cultured with another key-stone oral pathogen Porphyromonas gingivalis under anaerobic conditions and oxidative stress conditions.
Project description:adt06-03-mkk2 - mkk2_mkk2_and_wrky19_cold_time_course - early response targets of MKK2 upon cold stress treatment and its role in adaptation. - seedlings were put to 4 ° comparing wild type ColO versus mkk2 knockouts, MKK2 overexpressors and wrky19 knockouts. Keywords: time course,wt vs mutant comparison