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03 Jun 2020

Collaboration Yields Insight on Role of Metabolism in Bacterial Growth

By nickwiecien

Bacterial biofilms are everywhere in nature and play an important role in many clinical, industrial, and ecological settings. Although much is known about the transcriptional regulatory networks that control biofilm formation in model bacteria such as Bacillus subtilis, very little is known about the role of metabolism in this process. To address this important knowledge gap, this study used a time-resolved analysis of the metabolic changes associated with bacterial biofilm development in B. subtilis by combining metabolomic, transcriptomic, and proteomic analyses. This report serves as a unique resource for future studies and will be relevant to future research in microbial physiology and metabolism. The full publication can be found here.

25 Apr 2020

Glycoproteome and Surfaceome Changes in Isogenic Cells

By nickwiecien

Leung et al (2020) investigated key cell surface regions and their interactions with the extracellular environment in order to understand how to develop possible cancer immunotherapy drugs in a recent issue of Proceedings of the National Academy of Sciences.

Specifically, in order to understand how oncogenes remodel isogenic cells, researchers conducted quantitative proteomics on N-linked glycoproteins. Here, researchers observed how a large number of surface proteins were changed in isogenic breast epithelial cell lines to express oncogenes.

In addition to looking at surfaceome data with applied glycoproteoics, researchers also applied activated ion electron transfer dissociation (AI-ETD). Here. researchers found changes to the glycoproteome, as induced by the oncogenes.

Researchers said that these studies could help illustrate how specific oncogenes can remodel both the surfaceome and the glycoproteome in cells. Additionally, this research can help in the production of further cancer antibody drug discovery research.

Image of abstract
24 Mar 2020

High CO2 Associated with Downregulation of Skeletal Muscle Synthesis and Ribosomal Biogenesis

By nickwiecien

High levels of CO2 downregulates skeletal muscle protein anabolism, according to a recent paper by TC Korponay et al (2020)  in the American Journal of American Journal of Respiratory Cell and Molecular Biology.

Two independent conditions are associated with worse outcomes in patients with chronic pulmonary diseases; the retention of a high amount of Co2 (also called “hypercapnia”) and skeletal muscle wasting (also associated with worse outcomes in acute pulmonary disease).
Due to the current lack of research on the role of high CO2 levels in regulating skeletal muscle anabolism, researchers sought to investigate the role of high CO2 levels in weakening skeletal muscle protein synthesis in both patients and mice.

Researchers found that locomotor muscles from patients with chronic CO2 retention had decreased ribosomal gene expression in comparison to patients who did not retain CO2 to the same extent. Additionally, researchers found that mice in a high-CO2 environment had downregulated ribosomal biogenesis in their skeletal muscles, as well as decreased protein synthesis.

Evidently, researchers found that there was an impact of high CO2 levels on skeletal muscle synthesis and anabolism. Researchers suggested future studies focusing on ribosomal biogensis and protein synthesis to counteract the impacts of high CO2 on skeletal muscles.

17 Mar 2020

MS-Helios for Compact Data Visualization of Multi-omic Datasets

By nickwiecien

MS-Helios is an easy-to-use command line tool which works to solve the challenge of data analysis and visualization in the face of high-resolution mass spectrometery.

Though high-resolution mass spectrometry can identify hundreds of metabolites and thousands of proteins, this can make data analysis and visualization hard to do.

MS-Helios is a solution, allowing for compact data representation and reduced dimensionality. This tool also allows non-experts and experts alike to generate data and configuration files and publish high-quality, circular plots with Circos.

This software is available for download here.
The manuscript for MS-Helios can be viewed here.

10 Mar 2020

Investigating Abnormal Chromosome Tolerance in Wild Yeast Cells

By nickwiecien

Hose et al (2020) researched the genetic basis of aneuploidy tolerance in wild yeast in a recent edition of Elife.

Aneuploidy, or the abnormal chromosome numbers in a cell, is a harmful condition in developmental stages of wild yeast, yet is also common in plant cancers and pathogenic fungi. It is interesting to note that aneuploidy tolerance varies; for instance, researchers found that some wild isolates of baker’s yeast can tolerate chromosome amplification, while laboratory strains cannot. 

To study the genetic basis of how well wild yeast can tolerate aneuploidy, researchers mapped the genetic basis to Ssd1, an RNA-binding translational regulator that functions in wild strains but is defective in a laboratory strain “W303.” 

Researchers found that aneuploidy tolerance is enabled via a role for Ssd1 in mitochondrial physiology, such as binding and regulating nuclear-encoded mitochondrial mRNAs.


27 Feb 2020

Transgenic animal models demonstrate that mice have similar COPD-related skeletal muscle dysfunction as humans

By nickwiecien

Balnis et al (2020) recently studied the mechanisms of COPD-related skeletal muscle dysfunction using an established transgenic animal model of COPD in a recently published paper in the Journal of Applied Physiology. 

Patients with chronic obstructive pulmonary disease (COPD), a disease that is characterized by obstructed airflow to the lungs and is associated with long-term exposure to cigarette smoke, often also develop skeletal muscle dysfunction. Overall, the comorbidity of COPD and skeletal muscle dysfunction is associated with outcomes such as poor health and mortality.

While some research has suggested that skeletal muscle dysfunction may be the result of COPD-related conditions, such as protein degradation and metabolic disruption, there is still poor understanding on what mechanisms would regulate these processes, as there is little to no research on a validated animal model of pulmonary emphysema. Therefore, Balnis et al (2020) sought to use such a model based on inducible UL-13-driven pulmonary emphysema (IL-13TG) to study the mechanisms of skeletal muscle dysfunction.

Using a transgenic mouse model, researchers found that the skeletal muscles of emphysematous mice are similar to those developed by human patients with COPD. For instance, both groups develop muscular atrophy and have decreased oxygen consumption. Within skeletal muscles, both groups also had downregulated ATP binding and bioenergetics.

Researchers concluded that transgenic animal models of COPD are useful to understand skeletal-muscle dysfunction in humans.

06 Feb 2020

A Strategy for Increasing Analytical Throughput in Quantitative Proteomics

By nickwiecien

Zhong et al (2019) developed a novel strategy aimed towards solving challenges in absolute quantification, and detailed these efforts in a recent issue of Analytical Chemistry.

Absolute quantification is both an effective technique– which allows for robust results in proteomics research– and a challenging one. Problems that absolute quantification presents include low specificity in complex backgrounds, limited analytical throughput and wide dynamic range.

To solve these issues, Zhong et al (2019) developed hybrid offset-triggered multiplex absolute quantification (HOTMAQ), a strategy which increases the analytical throughput (the increase in analysis production rate) of targeted quantitative proteomics by up to 12 times. This technique accomplishes this by using mass-difference and isobaric tags to create an internal standard curve in the MS1 precursor scan, identify peptides at the MS2 level, and mass offset-trigger the quantification of target proteins in synchronous precursor selection at the MS3 level. All of this is accomplished at the same time. 

Because HOTMAQ results in greater quantitative performance, higher flexibility and quicker analysis rate, HOTMAQ is a strategy that can easily be applied to target peptidomics, proteomics, and phosphoproteomics.

Graphical Abstract, demonstrating the technique of hybrid offset-triggered multiplex absolute quantification (HOTMAQ). "Zhong, X., Q. Yu, F. Ma, D.C. Frost, L. Lu, Z. Chen, H. Zetterberg, C. Carlsson, O. Okonkwo, and L. Li, Hotmaq: A multiplexed absolute quantification method for targeted proteomics. Analytical Chemistry, 2019. 91(3): p. 2112-2119. PMCID: PMC6379083"
29 Jan 2020

3rd Annual North American Mass Spectrometry Summer School Registration Open

By nickwiecien

Join us for our third annual mass spectrometry summer school, which will be held in Madison, WI from June 15-18. We are proud to have assembled over a dozen world leading experts in mass spectrometry for this four-day course. Our goal is to provide our students, both from academia and industry, an engaging and inspiring program covering the latest in the application of mass spectrometry to omic analyses. Tutorial lectures range from mass analyzers to the basics of data analysis. Also planned are several hands-on workshops – aimed at both scientific and professional development. This program is made possible by generous funding from the National Science Foundation (Integrated Organismal Systems, Plant Genome Research Program, Grant No. 1546742) and the National Institutes of Health National Center for Quantitative Biology of Complex Systems (P41 GM108538). As such, there is no cost to participate.

Registration open through March 1, 2020: https://www.ncqbcs.com/resources/training/summer-school.

Please help us spread the word about this program by sharing the news with anyone who might have possible interest to participate.

See below for a list of expert instructors who will be leading the courses, as well as premium tutorial lectures and hands-on workshops that you can experience.

Thank you,
Josh Coon, Evgenia Shishkova, and Laura Van Toll (organizing committee)


Expert Instructors:

Scott McLuckey | Purdue University

Rachel Loo | University of California-Los Angeles

Joshua Coon | University of Wisconsin-Madison

Donald Hunt (invited) | University of Virginia

Shawnna Buttery | STAR Protocols

Jesper Velgaard Olsen | University of Copenhagen

Lingjun Li | University of Wisconsin-Madison

Jürgen Cox | Max Planck Institute of Biochemistry

Edward Huttlin | Harvard University

Susan Olesik | Ohio State University

Evgenia Shishkova | University of Wisconsin-Madison

Jessica Prenni | Colorado State University

Vicki Wysocki | Ohio State University

John Bowden | University of Florida

Tutorial Lectures:
Mass analyzers

Ionization

Tandem MS

Data acquisition

Quantification  

Experimental design

Separations  

PTMs

Metabolomics  

Top-down/Native MS

Lipidomics


Hands-on Workshops:
Mass analyzers

Spectral interpretation
Publishing and reviewing

Science writing

Science illustrations

22 Jan 2020

Software Highlight: LipiDex

By nickwiecien

LipiDex is a free and open-source software package offered by NCQBCS. This software package unifies all stages of the LC-MS/MS lipid identification process, and also utilizes intelligent data filtering to reduce manual result curation while increasing identification confidence.

One can use LipiDex to accomplish a variety of functions. For instance, one can create and manage custom in-silico lipid spectral libraries; model complex lipid MS/MS fragmentation using intuitive fragmentation templates; generate high-confidence MS/MS lipid identifications; annotate chromatographic peak tables with lipid identifications; and automatically filter peak tables for adduct peaks, in-source fragments and dimers.

Information on both LipiDex and Library Forge can be found here, and the software download is located here. Additionally, information on other software that the National Center for Quantitative Biology of Complex Systems offers can be found here.

Graphical Abstract depicting the software package lipidex accomplishing a variety of functions, such as the modeling of complex lipid ms/ms fragmentation, generation of high-confidence ms/ms lipid identifications, annotation of chromatographic peak tables, and the creation of in-silico lipid spectral libraries.
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