Podcasts about Proteome

Set of proteins that can be expressed by a genome, cell, tissue, or organism

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Best podcasts about Proteome

Latest podcast episodes about Proteome

Data in Biotech
Decoding the Dark Proteome: Biological Insights for Pharma with Dr. Jonathan Usuka from Sapient

Data in Biotech

Play Episode Listen Later Apr 2, 2025 46:45


In this episode of the Data and Biotech Podcast, host Ross Katz sits down with Dr. Jonathan Usuka to discuss Usuka's extensive background in bioinformatics and genomics, leading to his current role as CEO of Sapient.  The conversation dives into the importance of deep molecular characterization of diseases, the role of proteomics and metabolomics in drug discovery, and the gaps between real-world data and clinical trial data.  As a leader with a small but impactful team, Jonathan discusses the complexities of the dark proteome and metabolites, emphasizing the opportunity for deeper biological insights in pharmaceutical research using repeated, deep profiling of the same cohorts of patients. Jonathan also explores how advancements in computational approaches allow Sapient to build a robust data foundation for insight generation in biopharma.  ​​What You'll Learn in This Episode: The significance of longitudinal patient samplingWhy we need robust conclusions in biotechnology How the role of the FDA is evolving for drug approval and personalized medicine applications Connect with Our Guest: Sponsor: CorrDyn, a data consultancyFind out more about Sapient Connect with Dr. Jonathan Usuka on LinkedIn Connect with Us: Follow the podcast for more insightful discussions on the latest in biotech and data science.Subscribe and leave a review if you enjoyed this episode!

The Genetics Podcast
EP 178: Expanding the human proteome to facilitate drug discovery with John Lepore of ProFound Therapeutics

The Genetics Podcast

Play Episode Listen Later Mar 13, 2025 39:37


This week on The Genetics Podcast, Patrick is joined by Dr. John Lepore, physician-scientist and CEO of ProFound Therapeutics. They discuss ProFound Tx's mission to expand the proteome to identify novel drug targets – which resulted in the ProFoundry atlas – and the ways in which John's diverse experiences inform his approach as a leader.Show Notes: 0:00 Intro to The Genetics Podcast00:59 Welcome to John02:01 John's background at GSK and his transition to drug discovery05:45 Establishing ProFound Therapeutics to expand the proteome and identify novel drug targets 08:27 Genomic origins of newly-identified proteins and the process of finding them09:49 Developing the ProFoundry atlas and integrating data across assays 15:27 Different approaches to inferring protein links and association to disease17:13 Collaboration with Pfizer to find regulators in the context of obesity18:04 Developing novel antibody-drug conjugates for cancer treatment20:27 Clarifying causality in proteomic data21:59 Approaching novel targets while considering industrial and business factors25:19 John's background as a cardiologist and how that impacts his current work27:26 Tips for biotech companies looking to be noticed by pharma for collaborations30:30 Considerations for investigating new and different therapeutic modalities and techniques33:39 How John consistently reinforces the translational angle as a business leader36:24 Closing remarks and future direction for ProFound TherapeuticsFind out moreProFound Therapeutics (https://www.profoundtx.com/)Please consider rating and reviewing us on your chosen podcast listening platform! https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link

Biblical Genetics
The Dark Proteome

Biblical Genetics

Play Episode Listen Later Feb 4, 2025 22:20


Even though it was completed a quarter century ago, geneticists still struggle to estimate the number of genes in the human genome. They went from ‘hundreds of thousands' to “22 thousand”, then more recently to “about 19,500”. The number, however, has just exploded. Tens of thousands of new genes with important functions were discovered hiding in the ‘junk DNA'. Dr Rob explains what these new findings mean to the creation-evolution debate. Links and notes: Carter 2025 The dark proteome https://creation.com/dark-proteome Carter 2024 The incredible shrinking human genome, http://biblicalgenetics.com/shrinking-genome/ Amaral et al. 2024 The status of the human gene catalogue, Nature 622(7981):41–47; https://pubmed.ncbi.nlm.nih.gov/37794265/ Prensner et al. 2024 What can Ribo-seq and proteomics tell us about the non-canonical proteome? https://www.biorxiv.org/content/10.1101/2023.05.16.541049v1 Pennisi 2024 ‘Dark proteome' survey reveals thousands of new human genes, Science 386(6725):951–952; https://pubmed.ncbi.nlm.nih.gov/39607933/ Podcast: http://biblicalgenetics.com/contra-creation-myths Carter et al. 2004 Cloning of anthozoan fluorescent protein genes, Comparative Biochemistry and Physiology, Part C 138:259–270; https://pubmed.ncbi.nlm.nih.gov/15533784 Matz et al. 1999 Fluorescent proteins from nonbioluminescent Anthozoa species, Nature Biotechnology 17(10):969–973; https://pubmed.ncbi.nlm.nih.gov/10504696/

Biblical Genetics
The Dark Proteome

Biblical Genetics

Play Episode Listen Later Feb 4, 2025 22:20


Even though it was completed a quarter century ago, geneticists still struggle to estimate the number of genes in the human genome. They went from ‘hundreds of thousands' to “22 thousand”, then more recently to “about 19,500”. The number, however, has just exploded. Tens of thousands of new genes with important functions were discovered hiding in the ‘junk DNA'. Dr Rob explains what these new findings mean to the creation-evolution debate. Links and notes: Carter 2025 The dark proteome https://creation.com/dark-proteome Carter 2024 The incredible shrinking human genome, https://biblicalgenetics.com/shrinking-genome/ Amaral et al. 2024 The status of the human gene catalogue, Nature 622(7981):41–47; https://pubmed.ncbi.nlm.nih.gov/37794265/ Prensner et al. 2024 What can Ribo-seq and proteomics tell us about the non-canonical proteome? https://www.biorxiv.org/content/10.1101/2023.05.16.541049v1 Pennisi 2024 ‘Dark proteome' survey reveals thousands of new human genes, Science 386(6725):951–952; https://pubmed.ncbi.nlm.nih.gov/39607933/ Podcast: https://biblicalgenetics.com/contra-creation-myths Carter et al. 2004 Cloning of anthozoan fluorescent protein genes, Comparative Biochemistry and Physiology, Part C 138:259–270; https://pubmed.ncbi.nlm.nih.gov/15533784 Matz et al. 1999 Fluorescent proteins from nonbioluminescent Anthozoa species, Nature Biotechnology 17(10):969–973; https://pubmed.ncbi.nlm.nih.gov/10504696/

This Week in Evolution
TWiEVO 107: One small step for cells, one giant step for cell kind

This Week in Evolution

Play Episode Listen Later Oct 30, 2024 92:29


Nels and Vincent discuss the origins of eukaryotes, with contributions from at least 3 bacteria (alphaproteobacteria) and a large contribution from DNA viruses with large genomes. Hosts: Nels Elde and Vincent Racaniello Subscribe (free): Apple Podcasts, RSS, email Become a patron of TWiEVO Links for this episode Join the MicrobeTV Discord server Complex symbiotic interactions during eukaryogenesis (bioRxiv) Timestamps by Jolene Science Picks Nels – Pathoplexus.org Vincent – Can science cure its addiction to plastic? Music on TWiEVO is performed by Trampled by Turtles Send your evolution questions and comments to twievo@microbe.tv

Progress, Potential, and Possibilities
Dr. Parag Mallick, PhD - Co-Founder, Nautilus Biotechnology - Unlocking The Complexity Of The Proteome For A New Era Of Scientific Discovery

Progress, Potential, and Possibilities

Play Episode Listen Later Aug 21, 2024 54:36


Send us a Text Message.Dr. Parag Mallick, Ph.D. is an Associate Professor at Stanford University ( https://profiles.stanford.edu/parag-mallick ) and Co-Founder of Nautilus Biotechnology ( https://www.nautilus.bio/ ), a development stage life sciences company, engaged in creating a platform technology for quantifying and unlocking the complexity of the proteome for a new era of scientific discovery. Originally trained as an engineer and biochemist, Dr. Mallick's research spans proteomics, computational and experimental systems biology, cancer biology and nanotechnology. Dr. Mallick received his B.S. in Computer Science from Washington University in St. Louis. He then obtained his Ph.D. from UCLA in Chemistry & Biochemistry, where he worked with Dr. David Eisenberg. He completed his post-doctoral studies at The Institute for Systems Biology with Dr. Ruedi Aebersold. Dr. Mallick's group has been pioneering systems-biology approaches towards understanding disease mechanisms, discovering biomarkers and enabling personalized medicine. Most recently, his group has been developing model-based and physics-based approaches to machine learning that enable learning over domains that span a wide range of time and length scales. Dr. Mallick has over 100 publications and holds patents in the fields of artificial intelligence, proteomics technology, biomarker development, and nanotechnology. Additionally, he serves as an advisor to numerous biotechnology and diagnostics companies and is an accomplished magician. Dr. Mallick is a member, and frequent performer at the prestigious Magic Castle in Hollywood. He has performed all over the world for clients ranging from A-List Celebrities to Fortune 500 companies.#ParagMallick #Proteomics #Proteome #StanfordUniversity #NautilusBiotechnology #LifeSciences #DrugDiscovery #Diagnostics #Cancer #Alzheimers #Ashwgandha #ProgressPotentialAndPossibilities #IraPastor #Podcast #Podcaster #ViralPodcast  #STEM #Innovation #Technology #Science #ResearchSupport the Show.

Business Of Biotech
Expanding The Proteome with ProFound's John Lepore, M.D.

Business Of Biotech

Play Episode Listen Later Jul 29, 2024 56:38 Transcription Available


We love to hear from our listeners. Send us a message. Flagship Pioneering's ProFound Therapeutics is on to something, and it could be something big. It began with a simple question:  What if more RNAs were being translated into proteins? Answering that question took ProFound deep into the translatome, where it's now studying the full compendium of RNA sequences that are being translated into proteins. Along the way, the young company is gaining confidence that its research will reveal important insight into potential therapeutic protein targets and medicines. On this episode of the Business of Biotech, ProFound CEO and Flagship Pioneering CEO-Partner John Lepore, M.D. shares the company's journey—and his—as a physician scientist-turned-founder.Register for Bioprocess Online's Bio Expo Live, being held July 30th through August 1st . This inaugural expo is a fantastic opportunity for biopharma companies and contract manufacturers to evaluate the latest and greatest from the comfort of your desktop or mobile device. Conveniently, we've broken down the lineup into Upstream Solutions July 30th, Downstream Solutions July 31st, and Quality, Analytical, and Data Solutions August 1st. It's absolutely free to register for this series of short, digestible, and interactive sessions -- just hit the links above to register for Bio Expo Live today!

Talking Techniques
Spatial analysis of the immune-cell-surface proteome at a single-cell resolution

Talking Techniques

Play Episode Listen Later Mar 22, 2024 23:58


The cell-surface proteome plays a critical role in immune-cell function; however, our ability to examine its interactions and spatial organization has previously been limited by available proteomic techniques. This episode explores the function of immune-cell membrane proteins and how the latest developments in spatial proteomics have enabled more detailed interrogation of these proteins and their spatial relationships.Our guest, Hanna van Ooijen, Immunology Application Scientist at Pixelgen Technologies guides us through the field, revealing a new technique that enables spatial analysis of the cell-surface proteome at a single-cell resolution and highlighting some exciting discoveries that it has facilitated.Contents:Introductions: 00:00-01:40Introducing Molecular Pixelation: 01:40-02:15Example applications of Molecular Pixelation: 02:15-03:20The role of membrane proteins in immune cell function: 03:20-07:25Traditional techniques to investigate cell membrane proteins: 07:15-10:20Recent improvements in investigative technology and our understanding of immunology: 10:20-11:10Challenges associated with current technologies: 11:10-13:50How Molecular Pixelation can address these challenges: 13:50-15:25Molecular Pixelation workflow: 15:25-17:55Tips for best practice when using molecular pixelation: 17:55-19:30Exciting discoveries using Molecular pixelations: 19:30-21:00Potential implications of molecular pixelation for the future of immunology: 21:00-24:00 Hosted on Acast. See acast.com/privacy for more information.

Empowered Patient Podcast
Platform Using Proteome Wide Screening Unlocks Opportunities to Target Hard-to-Drug Proteins with Dr. Ping Cao BridGene Biosciences TRANSCRIPT

Empowered Patient Podcast

Play Episode Listen Later Jan 25, 2024


Dr. Ping Cao, Co-Founder and CEO of BridGene Biosciences, has developed IMTAC, a platform that can identify molecule ligands for hard-to-drug targets. This platform allows for proteome-wide screening for drug candidates from a small molecule library and has identified over 4,000 protein targets providing numerous opportunities for drug development. The lead candidate, BGI-9004, is a TEAD inhibitor of multiple cancers. BridGene is also in partnership with Takeda to focus on neurodegenerative disorders.   Ping explains, "For small molecule discovery, the major challenge right now is the limited druggable space. Human proteome consists of over 20,000 proteins, and approximately 12,000 of them have been confirmed to play a role in human diseases and may become targets for precision therapy."   "However, statistics analysis shows drugs so far approved by the FDA only target less than 10% of proteins. In other words, most potential drug targets within human proteome do not have associated drugs. Those targets are called hard-to-drug targets due to their biological or structural characteristics. Also, there is less understanding of their mechanism, making them undruggable using traditional methods."   "The significance of proteome-wide screening is that it addresses two kinds of major challenges of drug discovery. One is that some protein drugs contain shadow-binding pockets. The second one is some protein drugs only form transient and temporary binding pockets in live cell environments. For these two types of drugs, by using the chemical proteome approach, we can identify ligands. The process is basically like BridGene's process called IMTAC. They consist of three main components." #BridGeneBio #UndruggableTargets #SmallMolecules #Takeda BridGenebio.com Listen to the podcast here

Empowered Patient Podcast
Platform Using Proteome Wide Screening Unlocks Opportunities to Target Hard-to-Drug Proteins with Dr. Ping Cao BridGene Biosciences

Empowered Patient Podcast

Play Episode Listen Later Jan 25, 2024 17:40


Dr. Ping Cao, Co-Founder and CEO of BridGene Biosciences, has developed IMTAC, a platform that can identify molecule ligands for hard-to-drug targets. This platform allows for proteome-wide screening for drug candidates from a small molecule library and has identified over 4,000 protein targets providing numerous opportunities for drug development. The lead candidate, BGI-9004, is a TEAD inhibitor of multiple cancers. BridGene is also in partnership with Takeda to focus on neurodegenerative disorders.   Ping explains, "For small molecule discovery, the major challenge right now is the limited druggable space. Human proteome consists of over 20,000 proteins, and approximately 12,000 of them have been confirmed to play a role in human diseases and may become targets for precision therapy."   "However, statistics analysis shows drugs so far approved by the FDA only target less than 10% of proteins. In other words, most potential drug targets within human proteome do not have associated drugs. Those targets are called hard-to-drug targets due to their biological or structural characteristics. Also, there is less understanding of their mechanism, making them undruggable using traditional methods."   "The significance of proteome-wide screening is that it addresses two kinds of major challenges of drug discovery. One is that some protein drugs contain shadow-binding pockets. The second one is some protein drugs only form transient and temporary binding pockets in live cell environments. For these two types of drugs, by using the chemical proteome approach, we can identify ligands. The process is basically like BridGene's process called IMTAC. They consist of three main components." #BridGeneBio #UndruggableTargets #SmallMolecules #Takeda BridGenebio.com Download the transcript here

Aging-US
Systemic Changes Induced by ASCOT in Plasma Proteome of Women With Impaired Ovarian Reserves

Aging-US

Play Episode Listen Later Jan 9, 2024 3:57


BUFFALO, NY- January 9, 2024 – A new #research paper was #published in Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 15, Issue 24, entitled, “Systemic changes induced by autologous stem cell ovarian transplant in plasma proteome of women with impaired ovarian reserves.” Patients with poor ovarian response (POR) and premature ovarian insufficiency (POI) are challenging to treat, with oocyte donation remaining as the only feasible option to achieve pregnancy in some cases. The Autologous stem cell ovarian transplantation (ASCOT) technique allows follicle development, enabling pregnancies and births of healthy babies in these patients. Previous research suggests that growth factors and cytokines secreted by stem cells are partially responsible for their regenerative properties. Indeed, ASCOT beneficial effects are associated with the presence of different bone marrow derived stem cell- secreted factors in plasma. In this new study, researchers Anna Buigues, Noelia Ramírez-Martin, Jessica Martínez, Nuria Pellicer, Marcos Meseguer, Antonio Pellicer, and Sonia Herraiz from IVIRMA Global Research Alliance aimed to assess whether ASCOT induces any modifications in the plasma proteomic profile of patients with impaired ovarian reserves. “In this study, we aimed to assess if the ASCOT technique modifies the signature of the human plasma proteome, reveal the mechanisms underlying its beneficial effects on the ovary, and identify key regulators of ovarian aging.” Discriminant analysis highlighted clear distinctions between the plasma proteome before (PRE), during stem cell mobilization and collection (APHERESIS) and three months after ASCOT (POST) in patients with POR and POI. Both the stem cell mobilization and ASCOT technique induced statistically significant modifications in the plasma composition, reversing some age-related protein expression changes. In the POR group, functional analysis revealed an enrichment in processes related to the complement cascade, immune system, and platelet degranulation, while in the POI group, enriched processes were also associated with responses to oxygen-containing compounds and growth hormones, and blood vessel maturation. “In conclusion, our findings highlight the potential proteins and biological processes that may promote the follicle activation and growth observed after ASCOT.” DOI - https://doi.org/10.18632/aging.205400 Corresponding author - Sonia Herraiz - sonia_herraiz@iislafe.es Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.205400 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, plasma proteomic profile, autologous stem cell ovarian transplantation, poor ovarian response, premature ovarian insufficiency About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at https://www.Aging-US.com​​ and connect with us: SoundCloud - https://soundcloud.com/Aging-Us Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM

Die Profis | radioeins
Deutschland, Monsun, Windeln, Regenwürmer und Proteome

Die Profis | radioeins

Play Episode Listen Later Oct 7, 2023 41:26


In "Die Profis" geht es um die Frage, wie gespalten Deutschland ist. Wir sprechen über die Veränderung des südamerikanischen Monsuns und die Auswirkungen dessen auf die Welt. Es geht außerdem um Windeln und wie man sie recyclen kann. Dr. Mark Benecke hat Wissenswertes über Regenwürmer für Sie. Wie Proteome und Zellen im Gewebe gemeinsam funktionieren - auch das erfahren Sie in dieser Ausgabe.

AWS Health Innovation Podcast
#64, Decoding & Navigating the Proteome with Serafim Batzoglou, Chief Data Officer of Seer

AWS Health Innovation Podcast

Play Episode Listen Later Oct 3, 2023 33:16


Seer is pioneering new ways to decode the secrets of the proteome, leveraging engineered nanoparticles to provide unbiased, deep, and large-scale access to this incredibly detailed landscape. Learn more on the latest episode of the AWS Health Innovation Podcast.

Proteomics in Proximity
Pan-cancer blood proteome profiling with María Bueno Álvez (SciLifeLab)

Proteomics in Proximity

Play Episode Listen Later Oct 3, 2023 42:49


Welcome to the Olink® Proteomics in Proximity podcast!  Below are some useful resources from this episode:  Published study of primary focusÁlvez MB, Edfors F, von Feilitzen K, Zwahlen M, Mardinoglu A, Edqvist PH, Sjöblom T, Lundin E, Rameika N, Enblad G, Lindman H, Höglund M, Hesselager G, Stålberg K, Enblad M, Simonson OE, Häggman M, Axelsson T, Åberg M, Nordlund J, Zhong W, Karlsson M, Gyllensten U, Ponten F, Fagerberg L, Uhlén M. Next generation pan-cancer blood proteome profiling using proximity extension assay. Nat Commun. 2023 Jul 18;14(1):4308. doi: 10.1038/s41467-023-39765-y. PMID: 37463882; PMCID: PMC10354027. https://pubmed.ncbi.nlm.nih.gov/37463882/  Laboratory, first author, and corresponding author of the study·         SciLifeLab, a collaborative resource for life scientists located in Sweden: https://www.scilifelab.se/·         María Bueno Álvez (first author), PhD student, Science for Life Laboratory (SciLifeLab): https://www.linkedin.com/in/mar%C3%ADa-bueno-%C3%A1lvez-33395b192/ ·         Dr. Mathias Uhlén (corresponding author), Professor of Microbiology, Royal Institute of Technology (KTH), Leader of the Human Protein Atlas, Founding director of the Science for Life Laboratory (SciLifeLab): https://www.kth.se/pro/sysbio/uhlen-group/researchers/mathias-uhlen-1.67763  Olink tools and software·         Olink® Explore 1536, the platform that measured proteins in this study with a next-generation sequencing (NGS) readout: https://olink.com/products-services/explore/·         Olink® Explore HT, Olink's newest solution for high-throughput biomarker discovery that measures 5300+ proteins simultaneously with minimal sample consumption: https://olink.com/products-services/exploreht/ ·         Olink® Insight, an open-access resource to accelerate protein biomarker discovery: https://insight.olink.com/ UK Biobank Pharma Proteomics Project (UKB-PPP), one of the world's largest scientific studies of blood protein biomarkers conducted to date·         Published article: Styrkarsdottir U, Lund SH, Thorleifsson G, Saevarsdottir S, Gudbjartsson DF, Thorsteinsdottir U, Stefansson K. Cartilage Acidic Protein 1 in Plasma Associates With Prevalent Osteoarthritis and Predicts Future Risk as Well as Progression to Joint Replacements: Results From the UK Biobank Resource. Arthritis Rheumatol. 2023 Apr;75(4):544-552. doi: 10.1002/art.42376. Epub 2022 Dec 28. PMID: 36239377. https://pubmed.ncbi.nlm.nih.gov/36239377/ ·         UKB-PPP website: https://www.ukbiobank.ac.uk/learn-more-about-uk-biobank/news/uk-biobank-launches-one-of-the-largest-scientific-studies  Analysis of UK Biobank proteomics data from cancer patients, with co-authors including Ruth C. Travis, Karl Smith-Byrne, and Joshua R. AtkinsPreprint article: Papier K, Atkins JR, Tong TYN, Gaitskell K, Desai T, Ogamba CF, Parsaeian M, Reeves GK, Mills IG, Key TJ, Smith-Byrne K, Travis RC. Identifying proteomic risk factors for cancer using prospective and exome analyses: 1,463 circulating proteins and risk of 19 cancers in the UK Biobank. medRxiv 2023.07.28.23293330; doi: https://doi.org/10.1101/2023.07.28.23293330. https://www.medrxiv.org/content/10.1101/2023.07.28.23293330v1 U-CAN Biobank, a prospective biobank of cancer patient biomaterial in SwedenGlimelius B, Melin B, Enblad G, Alafuzoff I, Beskow A, Ahlström H, Bill-Axelson A, Birgisson H, Björ O, Edqvist PH, Hansson T, Helleday T, Hellman P, Henriksson K, Hesselager G, Hultdin M, Häggman M, Höglund M, Jonsson H, Larsson C, Lindman H, Ljuslinder I, Mindus S, Nygren P, Pontén F, Riklund K, Rosenquist R, Sandin F, Schwenk JM, Stenling R, Stålberg K, Stålberg P, Sundström C, Thellenberg Karlsson C, Westermark B, Bergh A, Claesson-Welsh L, Palmqvist R, Sjöblom T. U-CAN: a prospective longitudinal collection of biomaterials and clinical information from adult cancer patients in Sweden. Acta Oncol. 2018 Feb;57(2):187-194. doi: 10.1080/0284186X.2017.1337926. Epub 2017 Jun 20. PMID: 28631533. https://pubmed.ncbi.nlm.nih.gov/28631533/  Galleri GRAIL test, a blood-based test that detects a biosignature shared by over 50 cancer types: https://grail.com/galleri-test/  Genotype-Tissue Expression (GTEx) project, a biobank and open-access database to study tissue-specific gene expression and regulation: https://www.gtexportal.org/home/ Human Protein Atlas (HPA), a Swedish-based program with the aim to map all human proteins using an integration of various omics technologies and provide these data freely available to the scientific community: https://www.proteinatlas.org/   Would you like to subscribe to the podcast on your favorite player or app? You can do so here:  Apple Podcasts: https://apple.co/3T0YbSm  Spotify Podcasts: https://open.spotify.com/show/2sZ2wxO...  Google Podcasts: https://podcasts.google.com/feed/aHR0...  Amazon Music: https://music.amazon.com/podcasts/d97...  Podcast Addict: https://podcastaddict.com/podcast/409...  Deezer: https://www.deezer.com/show/5178787  Player FM: https://player.fm/series/series-3396598   In case you were wondering, Proteomics in Proximity refers to the principle underlying Olink Proteomics assay technology called the Proximity Extension Assay (PEA), and more information about the assay and how it works can be found here: https://bit.ly/3Rt7YiY  For any questions regarding information Olink Proteomics, please email us at info@olink.com or visit our website: https://www.olink.com/ WHAT IS PROTEOMICS IN PROXIMITY?Proteomics in Proximity discusses the intersection of proteomics with genomics for drug target discovery, the application of proteomics to reveal disease biomarkers, and current trends in using proteomics to unlock biological mechanisms. Co-hosted by Olink's Dale Yuzuki, Cindy Lawley and Sarantis Chlamydas.

Talking Biotech Podcast
Innovations in High Throughput Proteomics - Dr. Parag Mallick

Talking Biotech Podcast

Play Episode Listen Later Jul 22, 2023 47:40


While many global genomics analyzes gene variants or RNA expression products, the levels of proteins are usually the most informative.  At the same time, quantifying proteins is relatively difficult, especially when trying to obtain a snapshot of the proteome from a single cell or tissue. Dr. Parag Mallick of Stanford University and Nautilus Biotechnology describes the utility of high-throughput proteomics, and how the technology incorporates a novel detection method and machine learning to quantify large suites of proteins. The applications are almost endless and present great opportunities to understand how accumulation of specific proteins relates to biological function or disease states. 

Progress, Potential, and Possibilities
Dr. Thomas Metz, Ph.D. - Pacific Northwest National Laboratory - Hunting for The Other 99% Of The Universe's Chemicals

Progress, Potential, and Possibilities

Play Episode Listen Later Jul 20, 2023 45:44


Dr. Thomas Metz, Ph.D. ( https://www.pnnl.gov/people/thomas-o-metz ) is Senior Scientist, Laboratory Fellow and Principal Investigator, in the Integrative Omics group, within the Biological Sciences Division, of the Pacific Northwest National Laboratory (PNNL), where his research focuses on development and applications of high throughput metabolomics and lipidomics methods, in conjunction with proteomics, to answer various biological questions. Currently, Dr. Metz is the director of the Pacific Northwest Advanced Compound Identification Core within the NIH Common Fund Metabolomics Program, co-PI of the Proteomics Laboratory for The Environmental Determinants of Diabetes in the Young consortium, Lead of the PNNL m/q Initiative, and an adjunct faculty member in the Department of Biochemistry and Biophysics at Oregon State University. With a BS in Biology, Frostburg State University, a BS in Chemistry, San Jose State University, and a PhD in Chemistry, University of South Carolina, Dr. Metz's work has resulted in more than 180 publications to date. Pacific Northwest National Laboratory is one of the United States Department of Energy national laboratories, managed by the Department of Energy's Office of Science. They are focused on advancing the frontiers of knowledge, taking on some of the world's greatest science and technology challenges. Distinctive strengths in chemistry, Earth sciences, biology, and data science are central to their scientific discovery mission and their research lays a foundation for innovations that advance sustainable energy through decarbonization and energy storage and enhance national security through nuclear materials and threat analyses. PNNL collaborates with academia in fundamental research and with industry to transition technologies to market. Support the show

PaperPlayer biorxiv neuroscience
Ts65Dn synaptic proteome partially recapitulates AD biochemical signature

PaperPlayer biorxiv neuroscience

Play Episode Listen Later Apr 25, 2023


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.25.538253v1?rss=1 Authors: Gomez de Salazar, M. Abstract: Down syndrome (DS), caused by human chromosome 21 trisomy, is one of the most common genetic causes of intellectual disabilities. Moreover, approximately 60-80% of individuals with Down Syndrome develop early onset Alzheimer s disease symptoms and neuropathology characterized by the deposition of senile plaques and neurofibrillary tangles. Spine loss and synaptic deficits are the main alterations present in both pathologies. The synaptic proteins that are altered in both pathologies have also been studied. However, a proteomic study comparing synaptic fractions from DS and AD patients is lacking. To address this aim, we optimized a biochemical subfractioning method to isolate postsynaptic fractions from the cortex of Ts65Dn Down syndrome murine model and the entorhinal cortex from AD subjects samples. These samples were used for further proteomic analysis to observe potential alterations in postsynaptic protein expression and protein-protein interaction networks. This study compared the Ts65Dn animal model and entorhinal cortex of AD subjects and revealed a common altered postsynaptic composition of the adult Ts65Dn mouse cortex and entorhinal cortex of AD subjects. These postsynaptic protein alterations might functionally underlie Ts65Dn-associated and AD-associated dendritic deterioration, microtubule organization, glutamatergic transmission, and phosphorylation alterations. They provide insight into the possible common pathological synaptic mechanisms of both diseases and the earliest stages of AD disease progression. Moreover, our proteomic data suggest potential drug targets for modulating the commonly altered postsynaptic mechanisms in DS and AD. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

PaperPlayer biorxiv neuroscience
Early-life stress exposure impacts the hippocampal synaptic proteome in a mouse model of Alzheimer's disease: age- and pathology-dependent effects on mitochondrial proteins

PaperPlayer biorxiv neuroscience

Play Episode Listen Later Apr 20, 2023


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.20.537660v1?rss=1 Authors: Kotah, J. M., Kater, M. S. J., Hoeijmakers, L., Brosens, N., Lesuis, S., Tandari, R., Marchetto, L., Yusaf, E., Smit, A., Lucassen, P., Krugers, H., Verheijen, M., Korosi, A. Abstract: Epidemiological evidence indicates that early life stress (ES) exposure increases the risk for later-life diseases, such as Alzheimer's disease (AD). Accordingly, we and others have shown that ES aggravates the development of, and response to, amyloid-beta (A{beta}) pathology in animal models. Moreover, ES-exposed transgenic APP/PS1 mice display deficits in both cognitive flexibility and synaptic function. As the mechanisms behind these changes were unclear, we here investigated how exposure to ES, using the limited nesting and bedding model, affects the synaptic proteome across 2 different ages in both wildtype and APP/PS1 transgenic mice. We found that, compared to wildtype mice, the hippocampal synaptosomes of APP/PS1 mice at an early pathological stage (4 months) showed a higher abundance of mitochondrial proteins and lower levels of proteins involved in actin dynamics. Interestingly, ES exposure in wildtype mice had similar effects on the level of mitochondrial and actin-related synaptosomal proteins at this age, whereas ES exposure had no additional effect on the synaptosomal proteome of early-stage APP/PS1 mice. Accordingly, ultrastructural analysis of the synapse using electron microscopy in a follow-up cohort showed fewer mitochondria in pre- and post-synaptic compartments of APP/PS1 and ES-exposed mice, respectively. At a later pathological stage (10 months), the hippocampal synaptic proteome of APP/PS1 mice revealed an upregulation of proteins related to A{beta} processing, that was accompanied by a downregulation of proteins related to postsynaptic receptor endocytosis. ES exposure no longer affected the synaptic proteome of wildtype animals by this age, whereas it affected the expression of astrocytic proteins involved in lipid metabolism in APP/PS1 mice. We confirmed a dysregulation of astrocyte protein expression in a separate cohort of 12-month-old mice, by immunostaining for the alpha subunit of the mitochondrial trifunctional protein and fatty acid synthase in astrocytes. In conclusion, our data suggest that ES and amyloidosis share pathogenic pathways involving synaptic mitochondrial dysfunction and astrocytic lipid metabolism. These pathways might be underlying contributors to the long-term aggravation of the APP/PS1 phenotype by ES, as well as to the ES-associated risk for AD progression. These data are publicly accessible online as a web app via https://amsterdamstudygroup.shinyapps.io/ES_Synaptosome_Proteomics_Visualizer/. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

PaperPlayer biorxiv neuroscience
Impact of inflammatory preconditioning on murine microglial proteome response induced by focal ischemic brain injury

PaperPlayer biorxiv neuroscience

Play Episode Listen Later Apr 13, 2023


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.13.536755v1?rss=1 Authors: Helbing, D. L., Haas, F., Cirri, E., Rahnis, N., Dau, T. T. D., Sacramento, E. K., Oraha, N., Boehm, L., Morrison, H., Bauer, R. Abstract: Preconditioning with LPS induces neuroprotection against subsequent cerebral ischemic injury, mainly involving innate immune pathways. Microglia are CNS-resident immune cells that respond early to danger signals through memory-like differential reprogramming. However, the cell-specific molecular mechanisms underlying preconditioning are not fully understood. To elucidate the distinct molecular mechanisms of preconditioning on microglia, we compared these cell-specific proteomic profiles in response to LPS preconditioning and without preconditioning and subsequent transient focal brain ischemia and reperfusion, using an established mouse model of transient focal brain ischemia and reperfusion. A proteomic workflow, based on isolated microglia obtained from mouse brains by cell sorting and coupled to mass spectrometry for identification and quantification, was applied. Our data confirm that LPS preconditioning induces marked neuroprotection, as indicated by a significant reduction in brain infarct volume. The established brain cell separation method was suitable for obtaining an enriched microglial cell fraction for valid proteomic analysis. The results show a significant impact of LPS preconditioning on microglial proteome patterns by type I interferons, presumably driven by the interferon cluster regulator proteins Stat1/2. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

PaperPlayer biorxiv neuroscience
Uncovering circadian rhythm disruptions of synaptic proteome signaling in prefrontal cortex and nucleus accumbens associated with opioid use disorder

PaperPlayer biorxiv neuroscience

Play Episode Listen Later Apr 7, 2023


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.07.536056v1?rss=1 Authors: Puig, S., Xue, X., Salisbury, R., Shelton, M. A., Kim, S.-M., Hildebrand, M. A., Glausier, J. R., Freyberg, Z., Tseng, G. C., Yocum, A. K., Lewis, D. A., Seney, M. L., MacDonald, M. L., Logan, R. W. Abstract: Opioid craving and the vulnerability to relapse is associated with severe and persistent disruptions to sleep and circadian rhythms. Investigations into the cellular and molecular pathways in the human brain underlying the relationship between circadian rhythms and OUD remain limited. In human subjects with OUD, previous transcriptomics work implicated a role for circadian regulation of synaptic processes in key cognitive- and reward-related brain regions, dorsolateral prefrontal cortex (DLPFC) and nucleus accumbens (NAc). To provide further insights into the synaptic alterations associated with OUD, we used mass-spectrometry based proteomics to deeply profile protein alterations in tissue homogenates and synaptosomes from both NAc and DLPFC of unaffected and OUD subjects. Between unaffected and OUD subjects, we identified 43 differentially expressed (DE) proteins in NAc homogenates and 55 DE proteins in DLPFC homogenates. In synaptosomes, we found 56 DE proteins in NAc of OUD subjects and 161 DE proteins in DLPFC. Examining synaptosome enrichment of specific proteins enabled us to identify brain region- and synapse-specific pathway alterations in NAc and DLPFC associated with OUD. Across both regions, we found OUD-associated protein alterations primarily in pathways involved in GABAergic and glutamatergic synaptic functions, as well as circadian rhythms. Using time-of-death (TOD) analyses, where the TOD of each subject is used as a time-point across a 24-hour cycle, we were able to map circadian-related changes in the synaptic proteomes in NAc and DLPFC associated with OUD. In OUD, TOD analysis revealed significant circadian changes in endoplasmic reticulum to Golgi vesicle-mediated transport and protein membrane trafficking in NAc synapses, accompanied by changes in platelet derived growth factor receptor beta signaling in DLPFC synapses. Together, our results lend further support for molecular disruption of circadian regulation of synaptic signaling in the human brain as a key factor in opioid addiction. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Everything Epigenetics
Epigenetic Scores for the Proteome with Danni Gadd

Everything Epigenetics

Play Episode Listen Later Mar 29, 2023 54:15 Transcription Available


The proteome is the collection of proteins that are present within a specific cell, tissue, or system within the body. Our circulating proteome refers to the proteins circulating in our bloodstream and is made up of proteins that are either produced in the circulatory system, or proteins that enter the bloodstream from other organs and tissues in the body.Why do we care about this? As we know, proteins are extremely important! They are influencer molecules that maintain our health, and they're also often the mediators of disease. Furthermore, protein biomarkers have been identified across many age-related morbidities. As proteins are the primary effectors of disease, connecting the epigenome, proteome, and time to disease onset may help to create new, predictive biological signatures.DNA methylation (DNAm) has been linked to the levels of proteins in our blood and the risk people have of developing chronic diseases. DNAm reflects the body's exposure to chronic stress and inflammation and while this process is dynamic, DNAm may be more stable than protein measures, which can be variable across multiple time points. DNAm scores for proteins could therefore be used to identify individuals with high-risk biological signatures, many years prior to disease diagnosis.In this week's Everything Epigenetics podcast, Danni and I chat about the circulating proteome, how machine learning can be used to create epigenetic scores, and how information from the blood can be used to stratify risk of disease. We focus on the results from a study Danni published last year that integrated epigenetic and protein measures from the blood to develop new biomarkers for disease prediction. Danni's work integrates these blood-based markers with the medical records of thousands of individuals to model disease onset. Danni is in the final year of her PhD, on the Wellcome Trust Translational Neuroscience programme at the University of Edinburgh. In this episode of Everything Epigenetics, you'll learn about: - Danni's neuroscience background and what got her interested in the field- Why the Wellcome Trust Translational Neuroscience programme at the University of Edinburgh was a perfect fit for her - A walkthrough of the central dogma - A review of DNA methylation - What the circulating proteome is and why it's important - The importance of proteins as biomarkers- The definition and importance of an EpiScore, a term that Danni coined- The strongest methylation signature we've seen to-date - Why using DNA methylation to predict protein levels may be useful- Considerations on using blood when investigating these markers - The definition and importance of protein quantitative trait loci - The cohorts Danni investigated in her paper “Epigenetic scores for the circulating proteome as tools for disease prediction”- How Danni applied machine learning methods in the context of cohort studies - How Danni created EpiScores for protein levels  - The value of using protein EpiScores for disease prediction and risk stratification - Inflammation as an important indicator of health- How EpiScores compare with polygenic risk scores- The importance of these risk scores in the context of age-related chronic disease - The challenges and future directions in Danni's work - How people can be involved in large-scale cohort studies- What's next for DanniWhere to find Danni: Twitter: https://twitter.com/dannigaddDanni's profile at the University of Edinburgh: Support the showThank you for joining us at the Everything Epigenetics Podcast and remember you have control over your Epigenetics, so tune in next time to learn more about how.

PaperPlayer biorxiv cell biology
Hepatic Lipid Droplet-Associated Proteome Changes Distinguish Dietary-Induced Fatty Liver from Insulin Resistance in Male Mice.

PaperPlayer biorxiv cell biology

Play Episode Listen Later Mar 10, 2023


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.03.09.531813v1?rss=1 Authors: van Woerkom, A., Harney, D. J., Nagarajan, S. R., Hakeem-Sanni, M. F., Lin, J., Hooke, M., Pulpitel, T., Cooney, G. J., Larance, M., Saunders, D. N., Brandon, A. E., Hoy, A. J. Abstract: Fatty liver is characterised by the expansion of lipid droplets and is associated with the development of many metabolic diseases, including insulin resistance, dyslipidaemia and cardiovascular disease. We assessed the morphology of hepatic lipid droplets and performed quantitative proteomics in lean, glucose-tolerant mice compared to high-fat diet (HFD) fed mice that displayed hepatic steatosis and glucose intolerance as well as high-starch diet (HStD) fed mice who exhibited similar levels of hepatic steatosis but remained glucose tolerant. Both HFD and HStD-fed mice had more and larger lipid droplets than Chow-fed animals. We observed striking differences in liver lipid droplet proteomes of HFD and HStD-fed mice compared to Chow-fed mice, with fewer differences between HFD and HStD. Taking advantage of our diet strategy, we identified a fatty liver lipid droplet proteome consisting of proteins common in HFD- and HStD-fed mice. Likewise, a proteome associated with glucose tolerance that included proteins common in Chow and HStD but not HFD-fed mice was identified. Notably, glucose intolerance was associated with changes in the ratio of adipose triglyceride lipase (ATGL) to perilipin 5 (PLIN5) in the lipid droplet proteome, suggesting dysregulation of neutral lipid homeostasis in glucose-intolerant fatty liver, which supports bioactive lipid synthesis and impairs hepatic insulin action. We conclude that our novel dietary approach uncouples ectopic lipid burden from insulin resistance-associated changes in the hepatic lipid droplet proteome. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Mendelspod Podcast
New Spatial Company Maps Cell Surface Proteome without Imaging

Mendelspod Podcast

Play Episode Listen Later Mar 8, 2023


Today we talk with Simon Fredriksson, CEO and co-founder of Pixelgen Technologies, a company just out of stealth offering spatial technology that maps cellular surface proteins at the single cell level. Called molecular pixelation, the breakthrough technology is designed to first target immune cells.

PaperPlayer biorxiv neuroscience
Eye proteome of Drosophila melanogaster

PaperPlayer biorxiv neuroscience

Play Episode Listen Later Mar 6, 2023


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.03.04.531088v1?rss=1 Authors: Kumar, M., Has, C., Lam-Kamath, K., Ayciriex, S., Dewett, D., Bashir, M., Poupault, C., Schuhmann, K., Knittelfelder, O., Raghuraman, B. K., Ahrends, R., Rister, J., Shevchenko, A. Abstract: The Drosophila melanogaster eye is a popular model to elucidate the molecular mechanisms that underlie the structure and function of the eye as well as the causes of retinopathies. For instance, the Drosophila eye has been used to investigate the impacts of ageing and environmental stresses such as light-induced damage or dietary deficiencies. Moreover, large-scale screens have isolated genes whose mutation causes morphological and functional ocular defects, which includes key components of the phototransduction cascade. However, the proteome of the Drosophila eye is poorly characterized. Here, we used GeLC-MS/MS to quantify 3516 proteins he adult Drosophila melanogaster eye and provide a generic and expandable resource for further genetic, pharmacological, and dietary studies. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

PaperPlayer biorxiv cell biology
A proximity-dependent biotinylation map of cytosol-facing organelle outer membrane proteome in living Arabidopsis cells

PaperPlayer biorxiv cell biology

Play Episode Listen Later Mar 4, 2023


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.03.03.531038v1?rss=1 Authors: Bao, X., Jia, H., Zhang, X., Zhao, Y., Li, X., Lin, P., Ma, C., Wang, P., Song, C.-P., Zhu, X. Abstract: The cytosol-facing outer membrane (OM) of organelles communicates with other cellular compartments to exchange proteins, metabolites and signaling molecules. Cellular surveillance systems also target OM-resident proteins to control organellar homeostasis and ensure cell survival under stress. Using traditional approaches to discover OM proteins and identify their dynamically interacting partners remains challenging. In this study, we developed an OM proximity labeling (OMPL) system using biotin ligase-mediated proximity biotinylation to map the proximity proteome of the OMs of mitochondria, chloroplasts, and peroxisomes in living Arabidopsis (Arabidopsis thaliana) cells. We demonstrate the power of this system with the discovery of cytosolic factors and OM receptor candidates involved in local protein translation and translocation, membrane contact sites, and organelle quality control. This system also performed admirably for the rapid isolation of intact mitochondria and peroxisomes. Our data support the notion that TOM20-3 is a candidate for both a mitochondrial and a chloroplast receptor, and that PEX11D is a candidate for a peroxisome receptor for the coupling of protein translation and import. OMPL-generated OM proximity proteomes are valuable sources of candidates for functional validation and suggest directions for further investigation of important questions in cell biology. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

PaperPlayer biorxiv neuroscience
Differential Effects of Cocaine and Morphine on the Diurnal Regulation of the Mouse Nucleus Accumbens Proteome

PaperPlayer biorxiv neuroscience

Play Episode Listen Later Mar 2, 2023


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.03.01.530696v1?rss=1 Authors: Becker-Krail, D., Ketchesin, K. D. D., Xue, X., Wilson, R., Lam, T. T., Williams, K., Nairn, A., Tseng, G., Logan, R. W. Abstract: Substance use disorders (SUDs) are associated with disruptions in sleep and circadian rhythms that persist during abstinence and may contribute to relapse risk. Repeated use of substances such as psychostimulants and opioids may lead to significant alterations in molecular rhythms in the nucleus accumbens (NAc), a brain region central to reward and motivation. Previous studies have identified rhythm alterations in the transcriptome of the NAc and other brain regions following the administration of psychostimulants or opioids. However, little is known about the impact of substance use on the diurnal rhythms of the proteome in the NAc. We used liquid chromatography coupled to tandem mass spectrometry-based (LC-MS/MS) quantitative proteomics, along with a data-independent acquisition (DIA) analysis pipeline, to investigate the effects of cocaine or morphine administration on diurnal rhythms of proteome in the mouse NAc. Overall, our data reveals cocaine and morphine differentially alters diurnal rhythms of the proteome in the NAc, with largely independent differentially expressed proteins dependent on time-of-day. Pathways enriched from cocaine altered protein rhythms were primarily associated with glucocorticoid signaling and metabolism, whereas morphine was associated with neuroinflammation. Collectively, these findings are the first to characterize the diurnal regulation of the NAc proteome and demonstrate a novel relationship between phase-dependent regulation of protein expression and the differential effects of cocaine and morphine on the NAc proteome. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

PaperPlayer biorxiv cell biology
Dynamic mapping of proteome trafficking within and between living cells by TransitID

PaperPlayer biorxiv cell biology

Play Episode Listen Later Feb 8, 2023


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.02.07.527548v1?rss=1 Authors: Qin, W., Cheah, J. S., Xu, C., Messing, J., Freibaum, B. D., Boeynaems, S., Taylor, J. P., Udeshi, N. D., Carr, S. A., Ting, A. Y. Abstract: The ability to map trafficking for thousands of endogenous proteins at once in living cells would reveal biology currently invisible to both microscopy and mass spectrometry. Here we report TransitID, a method for unbiased mapping of endogenous proteome trafficking with nanometer spatial resolution in living cells. Two proximity labeling (PL) enzymes, TurboID and APEX, are targeted to source and destination compartments, and PL with each enzyme is performed in tandem via sequential addition of their small-molecule substrates. Mass spectrometry identifies the proteins tagged by both enzymes. Using TransitID, we mapped proteome trafficking between cytosol and mitochondria, cytosol and nucleus, and nucleolus and stress granules, uncovering a role for stress granules in protecting the transcription factor JUN from oxidative stress. TransitID also identifies proteins that signal intercellularly between macrophages and cancer cells. TransitID introduces a powerful approach for distinguishing protein populations based on compartment or cell type of origin. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

PaperPlayer biorxiv cell biology
Shift in vacuolar to cytosolic regime of infecting Salmonella from a dual proteome perspective

PaperPlayer biorxiv cell biology

Play Episode Listen Later Feb 7, 2023


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.02.07.527450v1?rss=1 Authors: Fels, U., Willems, P., De Meyer, M., Gevaert, K., Van Damme, P. Abstract: By applying dual proteome profiling to Salmonella enterica serovar Typhimurium (S. Typhimurium) encounters with its epithelial host (here, S. Typhimurium infected human HeLa cells), a detailed interdependent and holistic proteomic perspective on host-pathogen interactions over a time course of infection was obtained. Data-independent acquisition (DIA)-based proteomics was found to outperform data-dependent acquisition (DDA) workflows, especially in identifying the downregulated bacterial proteome response during infection progression infection by permitting quantification of low abundant bacterial proteins at early times of infection at low bacterial infection load. S. Typhimurium invasion and replication specific proteomic signatures in epithelial cells revealed interdependent host/pathogen specific responses besides pointing to putative novel infection markers and signalling responses. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

The Bio Report
Searching the Dark Matter of the Proteome to Develop New Therapies

The Bio Report

Play Episode Listen Later Jan 5, 2023 28:20


ProFound Therapeutics has developed platform technology to catalogue and understand previously undetected human proteins and the role they play in health and disease. By focusing on proteins in the process of translation, the company said it has identified tens of thousands of undiscovered proteins that can provide untapped therapeutic targets. We spoke to Avak Kahvejian, co-founder and CEO of ProFound Therapeutics, about the company's platform technology, the vastness of the unexplored proteome it seeks to discover, and how this can lead to the development of breakthrough medicines.

PaperPlayer biorxiv cell biology
Simultaneous proteome localization and turnover analysis reveals spatiotemporal dynamics of unfolded protein responses

PaperPlayer biorxiv cell biology

Play Episode Listen Later Jan 4, 2023


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.01.04.521821v1?rss=1 Authors: Currie, J., Manda, V., Hidalgo, V., Ludwig, R. W., Lam, M. P. Y., Lau, E. Abstract: The functions of proteins depend on their spatial and temporal distributions, which are not directly measured by static protein abundance. Under protein misfolding stress, the unfolded protein response (UPR) pathway remediates proteostasis in part by altering the turnover kinetics and spatial distribution of proteins, yet a global view of these spatiotemporal changes has yet to emerge and it is unknown how they affect different cellular compartments and pathways. Here we describe a mass spectrometry-based proteomics strategy and data analysis pipeline, named Simultaneous Proteome Localization and Turnover (SPLAT), to measure concurrently the changes in protein turnover and subcellular distribution in the same experiment. Investigating two common UPR models of thapsigargin and tunicamycin challenge, we find that the global suppression of protein synthesis during UPR is dependent on subcellular localization, with more severe slowdown in lysosome vs. endoplasmic reticulum (ER) protein turnover. Most candidate translocation events affect pre-existing proteins and likely involve vesicular transport across endomembrane fractions including an expansion of an ER-derived vesicle (ERV) compartment containing RNA binding proteins and stress response proteins. In parallel, we observed specific translocations involving only newly synthesized protein pools that are indicative of endomembrane stalling. The translocation of a subclass of cell surface proteins to the endomembrane including EGFR and ITGAV upon UPR affects only heavy labeled proteins, which suggest their internalization is driven by nascent protein trafficking rather than ligand dependent endocytosis. The approach described here may be broadly useful for inferring the coordinations between spatial and temporal proteome regulations in normal and stressed cells. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

PaperPlayer biorxiv neuroscience
APOE genotype or presence of brain amyloid alters the plasma proteome in cognitively normal, elderly subjects

PaperPlayer biorxiv neuroscience

Play Episode Listen Later Dec 29, 2022


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.12.28.522119v1?rss=1 Authors: Philippi, S. M., BP, K., Raj, T., Castellano, J. M. Abstract: Background: Processes that drive Alzheimer's disease pathogenesis have long been considered to occur within the central nervous system, yet recent studies have bolstered the possibility that changes in the periphery may be relevant to the disease process. Accumulating evidence has suggested that proteins changing in the blood may be reliable indicators of disease within the brain. Recent advances in geroscience have identified potential mechanisms of blood-brain communication that modulate brain function in ways that could be harnessed for therapy. While blood-borne proteins associated with either youth or old age have been targeted to restore function to the aged brain, it remains unclear whether other dysfunctional systemic states can be exploited for similar benefits. Here we investigate whether APOE allelic variation or presence of brain amyloid are associated with distinct proteomic changes within the systemic environment and what molecular processes are associated with these changes. Methods: Using the SOMAscan assay, we measured 1,305 plasma proteins from 53 homozygous APOE3 and APOE4 subjects (mean age = 68 years; minimum = 54 years) who exhibited no cognitive impairment, some of whom can be categorized as harboring cerebral amyloid based on cerebrospinal fluid A{beta}42 measurements. Using the Dream R package for linear mixed effects modeling, we investigated possible contributions of either the APOE-{epsilon}4 allele or amyloid positivity to changes in the plasma proteome. Ontology-based pathway and module trait correlation analyses were performed to understand disrupted pathways that vary based on APOE genotype or amyloid positivity. Results: We found that expression of the APOE-{epsilon}4 allele produced distinct changes in the composition of the plasma proteome. Using both pathway enrichment analysis and weighted gene co-expression network analysis, we found that plasma proteins associated with APOE4 expression were linked to pathways related to atherosclerosis, lipid transport, the extracellular matrix, and synaptogenesis signaling. Independent of APOE4, we found that cognitively normal, amyloid-positive subjects exhibit distinct plasma proteome signatures associated with pathways previously linked to AD pathology, relative to amyloid-negative controls. Harboring brain amyloid was associated with plasma proteomic changes linked to dysfunction in blood-brain barrier and other neural cell types. Our results indicate that changes in the plasma proteome are related to possession of AD risk alleles, as well as the presence of amyloid pathology in subjects prior to the onset of symptoms. This work highlights the possibility that pathways in the systemic environment in certain risk contexts may be plausible targets to explore for modulating disease. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

PaperPlayer biorxiv cell biology
Shift of the insoluble content of the proteome in aging mouse brain

PaperPlayer biorxiv cell biology

Play Episode Listen Later Dec 14, 2022


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.12.13.520290v1?rss=1 Authors: Molzahn, C. M., Kuechler, E. R., Zemlyankina, I., Nieves, L., Ali, T., Cole, G., Wang, J., Albu, R. F., Zhu, M., Cashman, N., Gilch, S., Karsan, A., Lange, P. F., Gsponer, J., Mayor, T. Abstract: Aging and protein aggregation diseases are inextricably linked. During aging, cellular response to unfolded proteins are believed to decline which results in diminished protein homeostasis (proteostasis). Indeed, in model organisms, such as C. elegans, proteostatic decline with age has even been linked to the onset of aggregation of proteins in wild-type animals. However, this correlation has not been extensively characterized in aging mammals. To reveal the insoluble portion of the proteome, we analyzed the detergent-insoluble fraction of mouse brain tissues after high-speed centrifugation by quantitative mass spectrometry. We identified a cohort of 171 proteins enriched in the pellet fraction of older mice including the alpha crystallin small heat shock protein. We then performed a meta-analysis to compare features among distinct groups of detergent-insoluble proteins reported in the literature. Surprisingly, our analysis revealed that features associated with proteins found in the pellet fraction differ depending on the ages of the mice. In general, insoluble proteins from young models ( less than 15 weeks) were more likely to be RNA-binding, more disordered and more likely to be found in membraneless organelles. These traits become less prominent with age within the combined dataset, as proteins with more structure enter the pellet fraction. This analysis suggests that age-related changes to proteome organization lead a specific group of proteins to enter the pellet fraction as a result of loss of proteostasis. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

PaperPlayer biorxiv cell biology
Facioscapulohumeral muscular dystrophy is associated with altered myoblast proteome dynamics

PaperPlayer biorxiv cell biology

Play Episode Listen Later Dec 14, 2022


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.12.14.520394v1?rss=1 Authors: Nishimura, Y., Bittel, A. J., Stead, C. A., Chen, Y.-W., Burniston, J. G. Abstract: Proteomic studies in facioscapulohumeral muscular dystrophy (FSHD) could offer new insight to disease mechanisms underpinned by post-transcriptional processes. We used stable isotope (deuterium oxide; D2O) labelling and peptide mass spectrometry to investigate the abundance and turnover rates of proteins in cultured muscle cells from 2 individuals affected by FSHD and their unaffected siblings (UASb). We measured the abundance of 4485 proteins and the turnover rate of 2324 proteins in each (n = 4) myoblast sample. FSHD myoblasts exhibited a greater abundance but slower turnover rate of subunits of mitochondrial respiratory complexes and mitochondrial ribosomal proteins, which may indicate an accumulation of older less viable mitochondrial proteins in myoblasts from individuals affected by FSHD. Our results highlight the importance of post-transcriptional processes and protein turnover in FSHD pathology and provide a resource for the FSHD research community to explore this burgeoning aspect of FSHD. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Proteomics in Proximity
Discussing the Proteome with Dr. Karsten Suhre of Weill Cornell Medicine Qatar

Proteomics in Proximity

Play Episode Listen Later Dec 7, 2022 46:52


Primary reference: Suhre K, Sarwath H, Engelke R, Sohail MU, Cho SJ, Whalen W, Alvarez-Mulett S, Krumsiek J, Choi AMK, Schmidt F. Identification of Robust Protein Associations With COVID-19 Disease Based on Five Clinical Studies. Front Immunol. 2022 12:781100. doi:10.3389/fimmu.2021.781100Dr. Karsten Suhre's Weill Cornell Medicine laboratory page: https://vivo.weill.cornell.edu/display/cwid-kas2049Leukemia Inhibitory Factor reference: Loriot Y, Marabelle A, Guégan JP, et al. Plasma proteomics identifies leukemia inhibitory factor (LIF) as a novel predictive biomarker of immune-checkpoint blockade resistance. Ann Oncol. 2021 32(11):1381-1390. doi:10.1016/j.annonc.2021.08.1748In case you were wondering, Proteomics in Proximity refers to the principle underlying Olink Proteomics assay technology called the Proximity Extension Assay (PEA), and more information about the assay and how it works can be found here.Would you like to subscribe to the podcast on your favorite player or app? You can do so here: Apple Podcasts: https://apple.co/3T0YbSm Spotify Podcasts: https://open.spotify.com/show/2sZ2wxOqI4b4vSngkajLs8?si=d957d55c8db046f7 Google Podcasts: https://podcasts.google.com/feed/aHR0cHM6Ly9mZWVkcy50cmFuc2lzdG9yLmZtL3Byb3Rlb21pY3MtaW4tcHJveGltaXR5 Amazon Music: https://music.amazon.com/podcasts/d97ace94-f02b-4b37-9532-799548ef2840 Podcast Addict: https://podcastaddict.com/podcast/4098296 Deezer: https://www.deezer.com/show/5178787 Player FM: https://player.fm/series/series-3396598

PaperPlayer biorxiv neuroscience
The RNA Binding proteome of axonal mRNAs in sympathetic neurons

PaperPlayer biorxiv neuroscience

Play Episode Listen Later Nov 24, 2022


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.11.23.517728v1?rss=1 Authors: Luisier, R., Andreassi, C., Riccio, A. Abstract: Background Neurons are morphologically complex cells that rely on the compartmentalization of protein expression to develop and maintain their cytoarchitecture. Targeting of RNA transcripts to axons is one of the mechanisms that allows rapid local translation of proteins in response to extracellular signals. 3' untranslated regions (UTRs) of mRNA are non-coding sequences that play a critical role in determining transcript localisation and translation by interacting with specific RNA binding proteins (RBPs). However, how 3'UTRs contribute to mRNA metabolism and the nature of RBP complexes responsible for these functions remain elusive. Results We performed 3' end sequencing of RNA isolated from axons and cell bodies of sympathetic neurons exposed to either Nerve Growth factor (NGF) or Neurotrophin 3 (NT3). NGF and NT3 are growth factors essential for sympathetic neuron development that act through distinct signalling mechanisms. Whereas NT3 is thought to act only locally, NGF signals back from axons to the cell bodies. We discovered that both NGF and NT3 affect transcription and alternative polyadenylation and induce the localisation of specific 3'UTR isoforms to axons. The finding that many transcripts with short 3'UTR were detected only in axons suggest that these may undergo local post-transcriptional remodelling. The integration of our data with CLIP-sequencing data revealed that long 3'UTR isoforms associate with RBP complexes in the nucleus, and once in axons, regulate cytoplasmic 3'UTR isoform cleavage into shorter isoform. Conclusions Our findings shed new light on the complex interplay between nuclear polyadenylation, mRNA localisation and local 3'UTR remodelling in developing neurons. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

PaperPlayer biorxiv neuroscience
Subcellular proteome of radial glia reveals non-muscle myosins control basal endfeet to mediate interneuron organization

PaperPlayer biorxiv neuroscience

Play Episode Listen Later Nov 18, 2022


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.11.18.517018v1?rss=1 Authors: D'Arcy, B., Lennox, A., Manso Musso, C., Bracher, A., Escobar-Tomlienovich, C., Perez-Sanchez, S., Silver, D. L. Abstract: Radial glial cells (RGCs) are essential for the generation and organization of neurons in the cerebral cortex. RGCs have an elongated bipolar morphology with basal and apical endfeet which reside in distinct niches. Yet, how this subcellular compartmentalization of RGCs controls cortical development is largely unknown. Here, we employ in vivo proximity labeling using unfused BirA to generate the first subcellular proteome of RGCs and uncover new principles governing local control of cortical development. We discover a cohort of proteins that are significantly enriched in RGC basal endfeet, with MYH9 and MYH10 among the most abundant. Myh9 and Myh10 transcripts also localize to endfeet with distinct temporal dynamics. Although they each encode isoforms of nonmuscle myosin II heavy chain, Myh9 and Myh10 have drastically different requirements for RGC integrity. Myh9 loss from RGCs decreases branching complexity and causes endfoot protrusion through the basement membrane. In contrast, Myh10 controls endfoot adhesion, as mutants have unattached apical and basal endfeet. Finally, we show that Myh9- and Myh10-mediated regulation of RGC complexity and endfoot position non-cell autonomously controls interneuron number and organization in the marginal zone. Our study demonstrates the utility of in vivo proximity labeling for dissecting local control of complex systems, and reveals new mechanisms for dictating RGC integrity and cortical architecture. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

PaperPlayer biorxiv cell biology
A stable reference human transcriptome and proteome as a standard for reproducible omics experiments

PaperPlayer biorxiv cell biology

Play Episode Listen Later Nov 17, 2022


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.11.16.516732v1?rss=1 Authors: Lu, S., Lu, H., Zheng, T., Yuan, H., Du, H., Gao, Y., Liu, Y., Pan, X., Zhang, W., Fu, S., Sun, Z., Jin, J., He, Q.-Y., Chen, Y., Zhang, G. Abstract: In recent years, the development of high-throughput omics technology has greatly promoted the development of biomedicine. However, the poor reproducibility of omics techniques limits its application. It is necessary to use standard reference materials of complex RNAs or proteins to test and calibrate the accuracy and reproducibility of omics workflows. However, the transcriptome and proteome of most cell lines shift during culturing, which limits their applicability to serve as standard samples. In this study, we demonstrated that the human hepatocellular cell line MHCC97H has a very stable transcriptome (R2=0.966-0.995) and proteome (R2=0.934-0.976 for DDA, R2=0.942-0.986 for DIA) after 9 subculturing generations, which allows this stable standard sample to be stably produced on an industrial scale for several decades. Moreover, this stability was maintained across labs and platforms. In sum, our results justified a omics standard reference material and reference datasets for transcriptomic and proteomics research. This helps to further standardize the workflow and data quality of omics techniques and thus promotes the application of omics technology in precision medicine. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Preprints in Motion
RNA editing in squid; recoding the proteome with Kavita Rangan

Preprints in Motion

Play Episode Listen Later Nov 16, 2022 44:44


This week we discuss RNA editing in cephalopods with postdoc Kavita Rangan. Read the full preprint -> https://www.biorxiv.org/content/10.1101/2022.09.25.509396v1.full This episode was produced by Jonny Coates and edited by Tala Noun & John Howard. If you enjoyed this show then hit that subscribe button and leave a review (on Apple Podcasts or Spotify). If you love what we are trying to do then buy us a coffee https://www.buymeacoffee.com/preprints! Any contribution is greatly appreciated. For the latest podcast news and updates follow us on Twitter @MotionPod, Instagram @Motion_Pod or visit our website; www.preprintsinmotion.com. Produced by JEmJ Productions (find us on Twitter: Jonny @JACoates, Emma @ELWilson92, John @JohnDHoward8) and generously supported by ASAPbio (https://asapbio.org | @asapbio_).

Intelligent Design the Future
Powerful Protein Folding Algorithm AlphaFold Foiled by Singletons

Intelligent Design the Future

Play Episode Listen Later Nov 14, 2022 29:43


Today's ID the Future spotlights AlphaFold, an artificial intelligence program in the news for its impressive breakthroughs at predicting a protein's 3D structure from its amino acid sequence. Philosopher of Biology Paul Nelson walks listeners through the importance of this “amazing breakthrough,” as he describes it in a recent Evolution News article; but don't uncork the champagne bottles just yet. The reason, according to Nelson, is that while proteins, protein sequences, and protein folding promise to reveal much that is still mysterious in molecular biology, we now know that biological information involves far more than just an organism's proteome—that is, far more than the full suite of proteins expressed by an organism. Nelson uses analogies to manmade machines and cognates Read More › Source

PaperPlayer biorxiv cell biology
Data-Dependent Acquisition with Precursor Coisolation Improves Proteome Coverage and Measurement Throughput for Label-Free Single-Cell Proteomics

PaperPlayer biorxiv cell biology

Play Episode Listen Later Oct 19, 2022


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.10.18.512791v1?rss=1 Authors: Truong, T., Johnston, S. M., Webber, K., Boekweg, H., Lundgren, C., Liang, Y., Nydegger, A., Xie, X., Payne, S. H., Kelly, R. T. Abstract: The sensitivity of single-cell proteomics (SCP) has increased dramatically in recent years due to advances in experimental design, sample preparation, separations and mass spectrometry instrumentation. Further increasing the sensitivity of SCP methods and instrumentation will enable the study of proteins within single cells that are expressed at copy numbers too small to be measured by current methods. Here we combine efficient nanoPOTS sample preparation and ultra-low-flow liquid chromatography with a newly developed data acquisition and analysis scheme termed wide window acquisition (WWA) to quantify greater than 3,000 proteins from single cells in fast label-free analyses. WWA is based on data-dependent acquisition (DDA) but employs larger precursor isolation windows to intentionally co-isolate and co-fragment additional precursors along with the selected precursor. The resulting chimeric MS2 spectra are then resolved using the CHIMERYS search engine within Proteome Discoverer 3.0. Compared to standard DDA workflows, WWA employing isolation windows of 8-12 Th increases peptide and proteome coverage by ~28% and ~39%, respectively. For a 40-min LC gradient operated at ~15 nL/min, we identified an average of 2,150 proteins per single-cell-sized aliquots of protein digest directly from MS2 spectra, which increased to an average of 3,524 proteins including proteins identified with MS1-level feature matching. Reducing the active gradient to 20 min resulted in a modest 10% decrease in proteome coverage. We also compared the performance of WWA with DIA. DIA underperformed WWA in terms of proteome coverage, especially with faster separations. Average proteome coverage for single HeLa and K562 cells was respectively 1,758 and 1,642 based on MS2 identifications with 1% false discovery rate and 3042 and 2891 with MS1 feature matching. As such, WWA combined with efficient sample preparation and rapid separations extends the depths of the proteome that can be studied at the single-cell level. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

PaperPlayer biorxiv cell biology
Cell size contributes to single-cell proteome variation

PaperPlayer biorxiv cell biology

Play Episode Listen Later Oct 17, 2022


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.10.17.512548v1?rss=1 Authors: Lanz, M. C., Elias, J. E., Skotheim, J. M. Abstract: Accurate measurements of the molecular composition of single cells will be key to elucidating the relationship between gene expression and function in diverse cell types. One of the most important phenotypes that differs between cells is their size, which was recently shown to be an important determinant of proteome composition in populations of similarly sized cells. We therefore sought to test if the effects of cell size on protein concentrations were also evident in single cell proteomics data. Using the relative concentrations of histone proteins to estimate a cell's DNA-to-cell volume ratio, we found that cell size correlated with the cell-to-cell variance in two single cell proteome datasets, each acquired using different preparation and measurement platforms. Moreover, the proteome differences between small and large single cells significantly correlated with how cell size affects the proteomes of cultured cells measured in bulk. We therefore conclude that cell size accounts for a substantial amount of proteome heterogeneity in single cells and should be considered particularly when comparing cells of a similar type. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

PaperPlayer biorxiv cell biology
Metabolic rewiring of mitochondria in senescence revealed by time-resolved analysis of the mitochondrial proteome

PaperPlayer biorxiv cell biology

Play Episode Listen Later Oct 14, 2022


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.10.13.512077v1?rss=1 Authors: Kim, J. Y., Atanassov, I., Dethloff, F., Kroczek, L., Langer, T. Abstract: Mitochondrial dysfunction and cellular senescence are hallmarks of aging. However, the relationship between these two phenomena remains incompletely understood. In this study, we investigated the rewiring of mitochondria upon development of the senescent state in human IMR90 fibroblasts. Determining the bioenergetic activities and abundance of mitochondria, we demonstrate that senescent cells accumulate mitochondria with reduced OXPHOS activity, resulting in an overall increase of mitochondrial activities in senescent cells. Time-resolved proteomic analyses revealed extensive reprogramming of the mitochondrial proteome upon senescence development and allowed the identification of metabolic pathways that are rewired with different kinetics upon establishment of the senescent state. Among the early-responding pathways, the degradation of branched-chain amino acid (BCAA) was increased, while the one carbon-folate metabolism was decreased. Late-responding pathways include lipid metabolism and mitochondrial translation. These signatures were confirmed by metabolic tracing experiments, highlighting metabolic rewiring as a central feature of mitochondria in cellular senescence. Together, our data provide an unprecedentedly comprehensive view on the metabolic status of mitochondria in senescent cells and reveal how the mitochondrial proteome adapts to the induction of senescence. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

PaperPlayer biorxiv cell biology
Alterations in platelet proteome signature and impaired platelet integrin αIIbβ3 activation in patients with COVID-19

PaperPlayer biorxiv cell biology

Play Episode Listen Later Oct 12, 2022


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.10.12.511145v1?rss=1 Authors: Goudswaard, L. J., Williams, C. M., Khalil, J., Burley, K. L., Hamilton, F., Arnold, D., Milne, A., Lewis, P. A., Heesom, K. J., Mundell, S. J., Davidson, A. D., Poole, A. W., Hers, I. Abstract: BackgroundPatients with coronavirus disease-19 (COVID-19) are at increased risk of thrombosis, which is associated with altered platelet function and coagulopathy, contributing to excess mortality. ObjectivesWe aimed to characterise the mechanism of altered platelet function in COVID-19 patients. MethodsThe platelet proteome, platelet functional responses and platelet-neutrophil aggregates were compared between patients hospitalised with COVID-19 and healthy control subjects using Tandem Mass Tag (TMT) proteomic analysis, Western blotting and flow cytometry. ResultsCOVID-19 patients showed a different profile of platelet protein expression (858 altered out of 5773 quantified). Levels of COVID-19 plasma markers were enhanced in COVID-19 platelets. Gene ontology (GO) pathway analysis demonstrated that levels of granule secretory proteins were raised, whereas some platelet activation proteins, such as the thrombopoietin receptor and PKC, were lowered. Basally, COVID-19 platelets showed enhanced phosphatidylserine (PS) exposure, with unaltered integrin IIb{beta}3 activation and P-selectin expression. Agonist-stimulated integrin IIb{beta}3 activation and PS exposure, but not P-selectin expression, were significantly decreased in COVID-19 patients. COVID-19 patients had high levels of platelet-neutrophil aggregates, even under basal conditions, compared to controls. This interaction was disrupted by blocking P-selectin, demonstrating that platelet P-selectin is critical for the interaction. ConclusionsOverall, our data suggests the presence of two platelet populations in patients with COVID-19: one with circulating platelets with an altered proteome and reduced functional responses and another with P-selectin expressing neutrophil-associated platelets. Platelet driven thromboinflammation may therefore be one of the key factors enhancing the risk of thrombosis in COVID-19 patients. Essentials- COVID-19 patient platelet function and platelet proteins were compared with healthy controls - Proteomic analysis of platelets indicated that COVID-19 decreased platelet activation proteins - Agonist induced PS exposure and integrin IIb{beta}3 activation were impaired in COVID-19 - COVID-19 led to maximal levels of P-selectin dependent platelet-neutrophil aggregates Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

mAcademia - Science, More than Just Academia.
#50 - Finding new paths paved with proteomics - with Gali Arad and Eran Seger from Protai

mAcademia - Science, More than Just Academia.

Play Episode Listen Later Oct 11, 2022 53:36


Gali Arad and Eran Seger from Protai had talked to us about moving from their previous life in tech and academia into the fast pace of illuminating the druggable Proteome for better cures. Eran Seger is the Co-Founder and CEO of Protai, a fast-growing biotech startup sitting on the intersection of proteomics and machine learning to develop novel therapeutics for a variety of complex diseases. Eran is an experienced technology executive and entrepreneur with a strong technical background and over 15 years of tech leadership positions at the Israeli Intelligence forces and HighTech. Gali Arad, PhD is a Computational Biologist and the first employee of Protai, a drug discovery startup combining AI and proteomics to create intelligence-driven pharma. She is an end-to-end computational biology scientist, with broad experience in systems biology, data analysis, hands-on technological practice, and clinical samples handling. In her current role, Gali leads the scientific research, focused on target discovery and prioritization, and the collection and curation of Protai's data warehouse. She holds a Ph.D from Tel Aviv University, applying mass-spectrometry-based proteomics to study cancer heterogeneity. Her findings were published in top-tier scientific journals and emphasized the added value of clinical proteomics in the study of cancer. Music: Funkorama Kevin MacLeod (incompetech.com) Licensed under Creative Commons: By Attribution 3.0 License http://creativecommons.org/licenses/by/3.0/ --- Send in a voice message: https://anchor.fm/macademia/message

Careers in Discovery
Ian Pike, Proteome Sciences

Careers in Discovery

Play Episode Listen Later Sep 28, 2022 45:46


"It's one thing having an idea, but you've got to be able to make it and you've got to be able to sell it." Just one extract from a wealth of sound advice offered by Ian Pike, Chief Scientific Officer at Proteome Sciences, on the Careers in Discovery podcast. Ian also talked to us about how CROs have become a crucial part of drug discovery, the importance of serendipity, his one career regret and being willing to pivot in your vision for your working life. Enjoy!

The Bio Report
Mapping the Human Proteome

The Bio Report

Play Episode Listen Later Feb 24, 2022 25:33


Though it's been nearly 20 years since the Human Genome Project provided a blueprint for human biology, it still left much work to be done to understand health and disease at a molecular level. The Sweden-based Human Protein Atlas, which is seeking to map human proteins in cells, tissues, and organs, recently published significant updates to the open-access resource. We spoke to Mathias Uhlén, director of the Human Protein Atlas, about how the atlas is changing the diagnosis and treatment of disease, what's known about the human proteome to date, and how this understanding will be essential to brining about an era of precision medicine.

Don't Just Read the Guidelines
#9 Platelet ageing with Harriet Allan

Don't Just Read the Guidelines

Play Episode Listen Later Jan 5, 2022 45:10


On this episode, I discuss platelet ageing with Dr Harriet Allan, post-doctoral researcher at Queen Mary University of London. We discuss Harriet's recent paper: "Proteome and functional decline as platelets age in the circulation" (https://onlinelibrary.wiley.com/doi/10.1111/jth.15496) I also mentioned a really good podcast series on Dinosaurs which is extremely tenuously related to this topic... but it's great all the same! Here's the link: https://www.audible.co.uk/pd/A-Grown-Up-Guide-to-Dinosaurs-Podcast/B08DCWN9N9

The Skeptics' Guide to the Universe
The Skeptics Guide #798 - Oct 24 2020

The Skeptics' Guide to the Universe

Play Episode Listen Later Oct 24, 2020


RIP James Randi; Interview with Richard Wiseman; News Items: Mapping the Proteome, Room Temperature Superconductivity, Falling Biodiversity; Who's That Noisy; Science or Fiction