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Markus Ralser

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Markus Ralser
Markus Ralser, 2022
Born3 April 1980
NationalityItalian
Alma materUniversity of Salzburg
Max Planck Institute for Molecular Genetics
University of Cambridge
AwardsWellcome Beit Prize
EMBO Gold Medal
Scientific career
FieldsMetabolism
InstitutionsUniversity of Cambridge
Francis Crick Institute
Charité
University of Oxford
Websiteralser.group

Markus Ralser (born 3 April 1980 in Vipiteno, Italy) is an Italian biologist. His main research interest is metabolism of microorganisms. He is also known for his work on the origin of metabolism during the origin of life, and proteomics.

Life and career

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Prof. Ralser serves since 2019 as head of the Institute of Biochemistry at the Charité – Universitätsmedizin Berlin, Germany;[1] as well as since 2022 as group leader at the University of Oxford, UK.

He studied genetics and molecular biology in Salzburg, Austria. He completed his PhD in 2006 at the Max Planck Institute for Molecular Genetics in Berlin, Germany, studying neurodegenerative diseases. This was followed by a postdoctoral fellowship at the Vrije Universiteit Amsterdam, Netherlands, where he started to explore mass spectrometry. He returned to the MPI for Molecular Genetics in 2007 to become junior group leader, but in 2011 relocated his group to the University of Cambridge, UK. He relocated again, becoming group leader at the newly opened Francis Crick Institute in London in 2013 (senior group leader since 2019).[2] His group moved to Oxford in 2022.

Research

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Ralser's two research groups use LC–MS to analyze the proteomes and metabolomes of microorganisms. The main model organism is the baking yeast (Saccharomyces cerevisiae), but other species, such as pathogenic fungus Candida albicans and the fission yeast Schizosaccharomyces pombe, are used too.

His lab not only uses LC–MS, but also develops novel LC–MS methods and protocols that improve detection accuracy, speed, and throughput. Specializing in data-independent acquisition, the group has developed scanning SWATH MS[3] and Zeno SWATH MS[4] in collaboration with MS manufacturer SCIEX. Both methods greatly improve upon SWATH MS, which was developed in Switzerland in 2012.[5] The group additionally developed an acquisition method—DIA-NN—that uses neural networks.[6] But proteins and metabolites are not the only focus: in 2022 the lab developed a protocol for the accurate quantification of DNA methylation using LC–MS.[7]

Key research topics include:

  • Metabolic networks within cells.[8]
  • The exchange of metabolites between cells. The group found that yeast cells prefer to take up metabolites from the outside environment (the exometabolome) rather than produce their own, and that these cells can survive non-autonomously in a community, thus mutually depending on other community members for survival.[9]
  • The biochemistry of competing reactions within cells. The group generated a genome-scale enzyme-inhibition network in humans and revealed that compartmentalization in eukaryotes helps alleviate the extent of the self-inhibition.[10]
  • The role, function, and regulation of metabolic genes. This is achieved by analyzing the proteome and metabolome in a genome-wide collection of yeast gene deletion strains.[11][12]
  • Microbial cytogenetics. The group found that aneuploidy (abnormal chromosome number) is tolerated in yeast through a mechanism of dosage compensation: the expression of genes on aneuploid chromosomes is adjusted so as to produce a normal amount of protein.[13]
  • Metabolism-related protective mechanisms against oxidative stress. The group found, among others, that methionine, a known antioxidant, protects against oxidative stress through the pentose phosphate pathway.[14] Earlier, Ralser found that cells dynamically switch between glycolysis and the pentose phosphate pathway to supply the antioxidant machinery with electrons—a mechanism known as the glycolysis/pentose phosphate pathway transition, which is now considered the first-line cellular anti-stress mechanism across species.[15]
  • The evolution of central carbon metabolism, and non-enzymatic reactions in cellular metabolism.[16] The group found that key reactions of glycolysis, the pentose phosphate pathway,[17] and gluconeogenesis[18] can occur spontaneously, without enzyme catalysis, and in the ambient conditions that prevailed billions of years ago on Earth.
  • Metabolic mechanisms of resistance to antifungal drugs.[19]

During the COVID-19 pandemic the Ralser group developed a proteomics panel assay for the assessment of disease severity and for the prediction of outcome.[20] The assay quantifies 50 peptides derived from 30 proteins found in a patient's blood plasma. The lab found that these proteins can serve as markers: their abundance strongly correlates with COVID-19 severity and outcome. The assay can be performed at a routine clinical laboratory, and has become commercially available.

As of January 2023, Ralser has published nearly 200 peer-reviewed articles that have been cited more than 13,000 times.[21]

Awards

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References

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  1. ^ "Institute of Biochemisty". Charitė – Universitätsmedizin Berlin. 3 January 2023.
  2. ^ "The Ralser Lab". Francis Crick Institute. Retrieved 3 January 2023.
  3. ^ Messner, Christoph B.; Demichev, Vadim; Bloomfield, Nic; Yu, Jason S. L.; White, Matthew; Kreidl, Marco; Egger, Anna-Sophia; Freiwald, Anja; Ivosev, Gordana; Wasim, Fras; Zelezniak, Aleksej; Jürgens, Linda; Suttorp, Norbert; Sander, Leif Erik; Kurth, Florian (July 2021). "Ultra-fast proteomics with Scanning SWATH". Nature Biotechnology. 39 (7): 846–854. doi:10.1038/s41587-021-00860-4. ISSN 1546-1696. PMC 7611254. PMID 33767396.
  4. ^ Wang, Ziyue; Mülleder, Michael; Batruch, Ihor; Chelur, Anjali; Textoris-Taube, Kathrin; Schwecke, Torsten; Hartl, Johannes; Causon, Jason; Castro-Perez, Jose; Demichev, Vadim; Tate, Stephen; Ralser, Markus (14 April 2022). "High-throughput proteomics of nanogram-scale samples with Zeno SWATH DIA". eLife. 11: 2022.04.14.488299. bioRxiv 10.1101/2022.04.14.488299. doi:10.7554/elife.83947. PMC 9711518. PMID 36449390.
  5. ^ Gillet, Ludovic C.; Navarro, Pedro; Tate, Stephen; Röst, Hannes; Selevsek, Nathalie; Reiter, Lukas; Bonner, Ron; Aebersold, Ruedi (1 June 2012). "Targeted Data Extraction of the MS/MS Spectra Generated by Data-independent Acquisition: A New Concept for Consistent and Accurate Proteome Analysis *". Molecular & Cellular Proteomics. 11 (6): O111.016717. doi:10.1074/mcp.O111.016717. ISSN 1535-9476. PMC 3433915. PMID 22261725.
  6. ^ Demichev, Vadim; Messner, Christoph B.; Vernardis, Spyros I.; Lilley, Kathryn S.; Ralser, Markus (January 2020). "DIA-NN: neural networks and interference correction enable deep proteome coverage in high throughput". Nature Methods. 17 (1): 41–44. doi:10.1038/s41592-019-0638-x. ISSN 1548-7105. PMC 6949130. PMID 31768060.
  7. ^ Varma, Sreejith Jayasree; Calvani, Enrica; Grüning, Nana-Maria; Messner, Christoph B; Grayson, Nicholas; Capuano, Floriana; Mülleder, Michael; Ralser, Markus (28 July 2022). Tyler, Jessica K (ed.). "Global analysis of cytosine and adenine DNA modifications across the tree of life". eLife. 11: e81002. doi:10.7554/eLife.81002. ISSN 2050-084X. PMC 9333990. PMID 35900202.
  8. ^ Ralser, Markus; Varma, Sreejith J.; Notebaart, Richard A. (1 December 2021). "The evolution of the metabolic network over long timelines". Current Opinion in Systems Biology. 28: 100402. doi:10.1016/j.coisb.2021.100402. ISSN 2452-3100. S2CID 239505820.
  9. ^ Campbell, Kate; Vowinckel, Jakob; Mülleder, Michael; Malmsheimer, Silke; Lawrence, Nicola; Calvani, Enrica; Miller-Fleming, Leonor; Alam, Mohammad T; Christen, Stefan; Keller, Markus A; Ralser, Markus (26 October 2015). Balasubramanian, Mohan (ed.). "Self-establishing communities enable cooperative metabolite exchange in a eukaryote". eLife. 4: e09943. doi:10.7554/eLife.09943. ISSN 2050-084X. PMC 4695387. PMID 26499891.
  10. ^ Alam, Mohammad Tauqeer; Olin-Sandoval, Viridiana; Stincone, Anna; Keller, Markus A.; Zelezniak, Aleksej; Luisi, Ben F.; Ralser, Markus (10 July 2017). "The self-inhibitory nature of metabolic networks and its alleviation through compartmentalization". Nature Communications. 8 (1): 16018. Bibcode:2017NatCo...816018A. doi:10.1038/ncomms16018. ISSN 2041-1723. PMC 5508129. PMID 28691704.
  11. ^ Mülleder, Michael; Calvani, Enrica; Alam, Mohammad Tauqeer; Wang, Richard Kangda; Eckerstorfer, Florian; Zelezniak, Aleksej; Ralser, Markus (6 October 2016). "Functional Metabolomics Describes the Yeast Biosynthetic Regulome". Cell. 167 (2): 553–565.e12. doi:10.1016/j.cell.2016.09.007. PMC 5055083. PMID 27693354.
  12. ^ Messner, Christoph B.; Demichev, Vadim; Muenzner, Julia; Aulakh, Simran; Röhl, Annika; Herrera-Domínguez, Lucía; Egger, Anna-Sophia; Kamrad, Stephan; Lemke, Oliver; Calvani, Enrica; Mülleder, Michael; Lilley, Kathryn S.; Kustatscher, Georg; Ralser, Markus (18 May 2022). "The Proteomic Landscape of Genome-Wide Genetic Perturbations": 2022.05.17.492318. doi:10.1101/2022.05.17.492318. hdl:20.500.11820/bd58332b-7ec5-4b1f-93a8-4aaf0a055d53. S2CID 248923566. {{cite journal}}: Cite journal requires |journal= (help)
  13. ^ Muenzner, Julia; Trébulle, Pauline; Agostini, Federica; Messner, Christoph B.; Steger, Martin; Lehmann, Andrea; Caudal, Elodie; Egger, Anna-Sophia; Amari, Fatma; Barthel, Natalie; Chiara, Matteo De; Mülleder, Michael; Demichev, Vadim; Liti, Gianni; Schacherer, Joseph (8 April 2022). "The natural diversity of the yeast proteome reveals chromosome-wide dosage compensation in aneuploids": 2022.04.06.487392. doi:10.1101/2022.04.06.487392. S2CID 248087625. {{cite journal}}: Cite journal requires |journal= (help)
  14. ^ Campbell, Kate; Vowinckel, Jakob; Keller, Markus A.; Ralser, Markus (1 April 2016). "Methionine Metabolism Alters Oxidative Stress Resistance via the Pentose Phosphate Pathway". Antioxidants & Redox Signaling. 24 (10): 543–547. doi:10.1089/ars.2015.6516. ISSN 1523-0864. PMC 4827311. PMID 26596469.
  15. ^ Ralser, Markus; Wamelink, Mirjam M C; Latkolik, Simone; Jansen, Erwin E W; Lehrach, Hans; Jakobs, Cornelis (1 July 2009). "Metabolic reconfiguration precedes transcriptional regulation in the antioxidant response". Nature Biotechnology. 27 (7): 604–605. doi:10.1038/nbt0709-604. ISSN 1087-0156. PMID 19587661. S2CID 205269373.
  16. ^ Keller, Markus A; Piedrafita, Gabriel; Ralser, Markus (1 August 2015). "The widespread role of non-enzymatic reactions in cellular metabolism". Current Opinion in Biotechnology. Systems biology • Nanobiotechnology. 34: 153–161. doi:10.1016/j.copbio.2014.12.020. ISSN 0958-1669. PMC 4728180. PMID 25617827.
  17. ^ Keller, Markus A; Turchyn, Alexandra V; Ralser, Markus (1 April 2014). "Non-enzymatic glycolysis and pentose phosphate pathway-like reactions in a plausible A rchean ocean". Molecular Systems Biology. 10 (4): 725. doi:10.1002/msb.20145228. ISSN 1744-4292. PMC 4023395. PMID 24771084.
  18. ^ Messner, Christoph B.; Driscoll, Paul C.; Piedrafita, Gabriel; De Volder, Michael F. L.; Ralser, Markus (11 July 2017). "Nonenzymatic gluconeogenesis-like formation of fructose 1,6-bisphosphate in ice". Proceedings of the National Academy of Sciences. 114 (28): 7403–7407. Bibcode:2017PNAS..114.7403M. doi:10.1073/pnas.1702274114. ISSN 0027-8424. PMC 5514728. PMID 28652321.
  19. ^ Yu, Jason S. L.; Correia-Melo, Clara; Zorrilla, Francisco; Herrera-Dominguez, Lucia; Wu, Mary Y.; Hartl, Johannes; Campbell, Kate; Blasche, Sonja; Kreidl, Marco; Egger, Anna-Sophia; Messner, Christoph B.; Demichev, Vadim; Freiwald, Anja; Mülleder, Michael; Howell, Michael (April 2022). "Microbial communities form rich extracellular metabolomes that foster metabolic interactions and promote drug tolerance". Nature Microbiology. 7 (4): 542–555. doi:10.1038/s41564-022-01072-5. ISSN 2058-5276. PMC 8975748. PMID 35314781.
  20. ^ Wang, Ziyue; Cryar, Adam; Lemke, Oliver; Tober-Lau, Pinkus; Ludwig, Daniela; Helbig, Elisa Theresa; Hippenstiel, Stefan; Sander, Leif-Erik; Blake, Daniel; Lane, Catherine S.; Sayers, Rebekah L.; Mueller, Christoph; Zeiser, Johannes; Townsend, StJohn; Demichev, Vadim (1 July 2022). "A multiplex protein panel assay for severity prediction and outcome prognosis in patients with COVID-19: An observational multi-cohort study". eClinicalMedicine. 49: 101495. doi:10.1016/j.eclinm.2022.101495. ISSN 2589-5370. PMC 9181834. PMID 35702332.
  21. ^ "Markus Ralser". Google Scholar. Retrieved 3 January 2023.
  22. ^ "BMC Research Awards". BioMed Central. Retrieved 3 January 2023.
  23. ^ "Grants awarded: Wellcome-Beit Prize". The Wellcome Trust. Retrieved 3 January 2023.
  24. ^ "Wissenschafts- und Forschungspreis an Ralser und Kustatscher überreicht". Autonome Provinz Bozen – Südtirol. 5 December 2014.
  25. ^ "Crick researcher awarded the Colworth Medal". The Francis Crick Institute. 30 March 2016.
  26. ^ "Sarah-Maria Fendt and Markus Ralser awarded EMBO Gold Medal 2020". EMBO. 14 October 2020.
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