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New features in Coenzyme Q identitifed

Coenzyme Q (CoQ), an essential lipid, is manufactured by virtually all cells, but how eukaryotes make the universal CoQ head group precursor 4-hydroxybenzoate (4-HB) from tyrosine is unknown. In this study, Robinson et al. study this pathway with genetic screens, targeted LC-MS, and chemical genetics. The results of their work defines new features of 4-HB synthesis in yeast, demonstrate the redundant nature of this pathway, and provide a foundation for further study.

Read the article: Defining intermediates and redundancies in coenzyme Q precursor biosynthesis

Introducing DiLeuPMP, a multiplexed isobaric labeling method

Glycosylation plays an important role in how the human body functions, including cell recognition, signaling, and immune response. While efforts have been devoted to the analysis of N-glycans, high-throughput quantitative analysis of O-glycans is underexplored. In this study, a multiplexed isobaric labeling method, DiLeuPMP, is introduced. This method combines the release and labeling of O-glycans in one step and achieves accurate MS2-based relative quantification. This method provides an effective and reliable approach for the profiling and high-throughput quantitative analysis of O-glycans in complex samples.

Read the article: DiLeuPMP: a multiplexed isobaric labeling method for quantitative analysis of O-glycans

Achieving a simplified, multi-omics workflow

An article by Yuchen He et. al. titled “Multi-omic Single-Shot Technology for Integrated Proteome and Lipidome Analysis” was recently published as one of the cover stories in Analytical Chemistry.

This article describes a technology to achieve broad and deep coverage of multiple molecular classes simultaneously through Multi-omics (proteome, lipidome, and metabolome) single-shot technology (MOST), requiring only one column, one LC-MS instrument, and a simplified workflow.

LipidGenie, a genome-guided lipid identification tool

Despite the crucial roles of lipids in metabolism, we are still in the early stages of annotating lipid species and their genetic basis. To help in this work, a team of researchers led by Vanessa Linke recently developed LipidGenie, an interactive, query-able resource for lipid identification. The research team used high-resolution liquid chromatography–tandem mass spectrometry to quantify 3,283 molecular features from the liver and plasma of outbred mice. These features were then mapped to 5,622 lipid quantitative trait loci, compiled and cross-referenced to the human genome.

Download the software and read the manuscript.

DiLeu isobaric tags achieves 21-plex quantification

Isobaric tags enable multiplexed quantitative analysis of many biological samples in a single LC-MS/MS experiment. As a cost-effective alternative to expensive commercial isobaric tagging reagents, the lab of Lingjun Li has developed their own custom “DiLeu” isobaric tags for quantitative proteomics. In this paper, Dustin Frost showcases a new generation of DiLeu tags that achieves 21-plex quantification in high-resolution HCD MS/MS spectra.

21-plex DiLeu Isobaric Tags for High-throughput Quantitative Proteomics. Analytical Chemistry.

Li lab collaboration yields insights into spinal cord stimulation for pain relief

A recent publication by Tilley et al titled Proteomic modulation in the dorsal spinal cord following spinal cord stimulation therapy in an in vivo neuropathic pain model, explores how Spinal cord stimulation (SCS) can provide relief for patients suffering from chronic pain, with less dependence on electrical interference. Recent evidence has been growing regarding molecular changes that are induced by SCS as being a key player in reversing the pain process. In this paper the effect of SCS on altering protein expression in spinal cord tissue using a proteomic analysis approach are observed.

Collaboration explores the role of N-glycans during vertebrate development

A collaboration with the lab of Norman Dovichi at the University of Notre Dame explores the role of N-glycans in biological processes during vertebrate development. In a recent publication, Quantitative Capillary Zone Electrophoresis-Mass Spectrometry Reveals the N-glycome Developmental Plan during Vertebrate Embryogenesis, they report on the first quantitative studies of both the expression of N-linked glycans at six early development stages and the expression of N-glycosylated peptides at two early development stages in the African clawed frog. In the study, N-Glycans were labeled with isobaric tandem mass tags and characterized using tandem mass spectrometry. Over two thirds of the N-glycoproteins identified in the late stage were associated with neuron projection morphogenesis, suggesting a vital role of the N-glycome in neuronal development.

Li lab collaboration explores noninvasive markers in prostate disease diagnosis

A recent collaboration between the labs of Lingjun Li and William Ricke explores the relationship between prostatic hyperplasia and related lower urinary tract symptoms in aging males and how noninvasive markers could be helpful in disease diagnosis. This proteomics study used a mouse model of hormone-induced urinary dysfunction to gain insight into the disease and supports the concept of noninvasive urinary biomarkers being a successful route for prostate disease diagnostics.

Thomas S, Hao L, DeLaney K, McLean D, Steinke L, Marker PC, Vezina CM, Li L, Ricke WA. Spatiotemporal proteomics reveals the molecular consequences of hormone treatment in a mouse model of lower urinary tract dysfunction. Journal of Proteome Research. 2020, 19(4):1375-1382.

Characterizing modified nucleic acids using negative electron transfer dissociation

A recent publication in Analytical Chemistry by Trenton Peters-Clarke et.al explores the promise of modified oligonucleotides for drug development, with small interfering RNAs (siRNA) and microRNAs gaining traction in the therapeutic market. Mass spectrometry (MS)-based analysis offers many benefits for characterizing modified nucleic acids. Negative electron transfer dissociation (NETD) has proven valuable in sequencing oligonucleotide anions, particularly because it can retain modifications while generating sequence-informative fragments.

Collaboration with Puglielli lab reveals AT-1 acts as metabolic regulator for acetyl-CoA

In a paper titled Acetyl-CoA Flux Regulates the Proteome and Acetyl-Proteome to Maintain Intracellular Metabolic Crosstalk, Inca Dieterich et al. of Prof Luigi Puglielli’s lab investigated two models of AT-1 dysregulation and altered acetyl-CoA flux: AT-1S113R/+ mice, a model of AT-1 haploin sufficiency, and AT-1 sTg mice, a model of AT-1 overexpression. The animals display distinct metabolic adaptation across intracellular compartments, including reprogramming of lipid metabolism and mitochondria bioenergetics. Our results suggest that AT-1 acts as an important metabolic regulator that maintains acetyl-CoA homeostasis by promoting functional crosstalk between different intracellular organelles.