Project description:This dataset presents a detailed lipidomics analysis of single bacterial strains from the Oligo-Mouse-Microbiota (OMM12) model, cultured in vitro, using high-resolution mass spectrometry in ESI negative (ESI-) mode.
Project description:Lipid alterations in the brain have been implicated in many neurodegenerative diseases. To facilitate comparative lipidomic research across brain diseases here we establish a data common named the Neurolipid Atlas, that we have pre-populated with isogenic induced pluripotent stem cell (iPSC)-derived lipidomics data for different brain diseases. Additionally, the resource contains lipidomics data of human and mouse brain tissue. Leveraging multiple datasets, we demonstrate that iPSC-derived neurons, microglia, and astrocytes exhibit distinct lipid profiles that recapitulate in vivo lipotypes. Notably, the AD risk gene ApoE4 drives cholesterol ester (CE) accumulation specifically in human astrocytes, and we also observe CE accumulation in whole human AD brain lipidomics. Multi-omics interrogation of iPSC-derived astrocytes revealed that altered cholesterol metabolism plays a major role in astrocyte interferon-dependent pathways such as the immunoproteasome and major histocompatibility complex class I antigen presentation. Our data commons, available at neurolipidatlas.com, and allows for data deposition by the community and provides a user-friendly tool and knowledge base for a better understanding of lipid dyshomeostasis in neurodegenerative diseases.
Project description:Outer membrane vesicle (OMV)-based vaccines have been employed worldwide in response to epidemic meningococcal disease outbreaks caused by Neisseria meningitidis. The complex composition of OMVs raises challenges in the identification of antigens which contribute to a protective immune response. Here, we measured total IgG antibody binding profiles to a dedicated antigen microarray using human sera from an open-label Phase II trial (NCT00962624) of 4CMenB (Bexsero), a licensed vaccine containing an OMV component. Significant IgG responses were observed against specific Outer Membrane Proteins (OMPs) from OMV antigens, including FetA, PorB, BamA and PorA. Partial Least Squares Regression was used to correlate IgG antibody reactivity profiles with the human complement-dependent killing of meningococci. We show that this approach is a powerful method to identify the potential contributions of OMV antigens - notably OpcA, FetA, PorA and PorB- towards serum bactericidal activity in human vaccinee serum against indicator strains, a recognised correlate of protection against invasive meningococcal disease
Project description:Lipidomics, proteomics and metabolomics characterization of the ontogeny of lipid, protein and metabolite changes during normal postnatal lung development
Project description:Early-life adversities increase vulnerability to substance use disorders, which are characterized by persistent, uncontrollable drive to seek drugs, often leading to relapse. Previously, we reported that early social isolation (ESI) during adolescence potentiates heroin-seeking in mice. However, the underlying neurobiology remains unknown. Here, we found that ESI aggravated heroin-induced neuronal dysfunction in prelimbic cortex (PrL) to ventral tegmental area (VTA) projecting neurons. Activating PrL->VTA projection attenuated ESI-potentiated heroin seeking, alongside normalized neuronal function. RNA-seq revealed that ESI and heroin convergently altered genes regulating morphogenesis and metabolism, with Tmsb4x (thymosin β4) as a key gene. ESI and heroin interaction affected genes regulating cell cycle and DNA damage response, with Mcm3 and Mcm7 (minichromosome maintenance proteins 3/7) as hubs. PrL thymosin β4 infusion or CRISPR-Cas9-mediated PrL->VTA projection-specific Mcm3/7 knockdown attenuated ESI-potentiated heroin-seeking and neuronal hypofunction. Our study suggests that ESI-potentiated heroin relapse is associated with neuronal and transcriptional alterations in PrL->VTA projection.
Project description:This project contains data of RP-LC-MS lipidomics of protein complex pull-downs (CoQ7, CoQ9, and CoQ7:CoQ9); data are associated with the manuscript titled "Structure and functionality of a multimeric human COQ7:COQ9 complex".