Markus Ralser

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Markus Ralser
Markus Ralser, 2022.jpg
Markus Ralser, 2022
Born3 April 1980
NationalityItalian
Alma mater University of Salzburg
Max Planck Institute for Molecular Genetics
University of Cambridge
AwardsWellcome Beit Prize
EMBO Gold Medal
Scientific career
Fields Metabolism
Institutions University of Cambridge
Francis Crick Institute
Charité
University of Oxford
Website ralser.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.

Contents

Life and career

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

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 LCMS. [7]

Key research topics include:

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

Related Research Articles

<span class="mw-page-title-main">Metabolic pathway</span> Linked series of chemical reactions occurring within a cell

In biochemistry, a metabolic pathway is a linked series of chemical reactions occurring within a cell. The reactants, products, and intermediates of an enzymatic reaction are known as metabolites, which are modified by a sequence of chemical reactions catalyzed by enzymes. In most cases of a metabolic pathway, the product of one enzyme acts as the substrate for the next. However, side products are considered waste and removed from the cell.

<span class="mw-page-title-main">Proteome</span> Set of proteins that can be expressed by a genome, cell, tissue, or organism

The proteome is the entire set of proteins that is, or can be, expressed by a genome, cell, tissue, or organism at a certain time. It is the set of expressed proteins in a given type of cell or organism, at a given time, under defined conditions. Proteomics is the study of the proteome.

<span class="mw-page-title-main">Peroxisome</span> Type of organelle

A peroxisome (IPA:[pɛɜˈɹɒksɪˌsoʊm]) is a membrane-bound organelle, a type of microbody, found in the cytoplasm of virtually all eukaryotic cells. Peroxisomes are oxidative organelles. Frequently, molecular oxygen serves as a co-substrate, from which hydrogen peroxide (H2O2) is then formed. Peroxisomes owe their name to hydrogen peroxide generating and scavenging activities. They perform key roles in lipid metabolism and the reduction of reactive oxygen species.

<span class="mw-page-title-main">Hexokinase</span> Class of enzymes

A hexokinase is an enzyme that irreversibly phosphorylates hexoses, forming hexose phosphate. In most organisms, glucose is the most important substrate for hexokinases, and glucose-6-phosphate is the most important product. Hexokinase possesses the ability to transfer an inorganic phosphate group from ATP to a substrate.

The iron–sulfur world hypothesis is a set of proposals for the origin of life and the early evolution of life advanced in a series of articles between 1988 and 1992 by Günter Wächtershäuser, a Munich patent lawyer with a degree in chemistry, who had been encouraged and supported by philosopher Karl R. Popper to publish his ideas. The hypothesis proposes that early life may have formed on the surface of iron sulfide minerals, hence the name. It was developed by retrodiction from extant biochemistry in conjunction with chemical experiments.

<span class="mw-page-title-main">Pyruvate kinase</span> Class of enzymes

Pyruvate kinase is the enzyme involved in the last step of glycolysis. It catalyzes the transfer of a phosphate group from phosphoenolpyruvate (PEP) to adenosine diphosphate (ADP), yielding one molecule of pyruvate and one molecule of ATP. Pyruvate kinase was inappropriately named before it was recognized that it did not directly catalyze phosphorylation of pyruvate, which does not occur under physiological conditions. Pyruvate kinase is present in four distinct, tissue-specific isozymes in animals, each consisting of particular kinetic properties necessary to accommodate the variations in metabolic requirements of diverse tissues.

In organic chemistry, a tetrose is a monosaccharide with 4 carbon atoms. They have either an aldehyde functional group in position 1 (aldotetroses) or a ketone group in position 2 (ketotetroses).

<span class="mw-page-title-main">Tandem mass spectrometry</span> Type of mass spectrometry

Tandem mass spectrometry, also known as MS/MS or MS2, is a technique in instrumental analysis where two or more stages of analysis using one or more mass analyzer are performed with an additional reaction step in between these analyses to increase their abilities to analyse chemical samples. A common use of tandem MS is the analysis of biomolecules, such as proteins and peptides.

<span class="mw-page-title-main">Nicotinamide adenine dinucleotide phosphate</span> Chemical compound

Nicotinamide adenine dinucleotide phosphate, abbreviated NADP+ or, in older notation, TPN (triphosphopyridine nucleotide), is a cofactor used in anabolic reactions, such as the Calvin cycle and lipid and nucleic acid syntheses, which require NADPH as a reducing agent ('hydrogen source'). NADPH is the reduced form, whereas NADP+ is the oxidized form. NADP+ is used by all forms of cellular life.

In oncology, the Warburg effect is the observation that most cancer cells release energy predominantly not through the 'usual' citric acid cycle and oxidative phosphorylation in the mitochondria as observed in normal cells, but through a less efficient process of 'anaerobic glycolysis' consisting of a high level of glucose uptake and glycolysis followed by lactic acid fermentation taking place in the cytosol, not the mitochondria, even in the presence of abundant oxygen. This observation was first published by Otto Heinrich Warburg, who was awarded the 1931 Nobel Prize in Physiology for his "discovery of the nature and mode of action of the respiratory enzyme". The precise mechanism and therapeutic implications of the Warburg effect, however, remain unclear.

<span class="mw-page-title-main">3-Phosphoglyceric acid</span> Chemical compound

3-Phosphoglyceric acid (3PG, 3-PGA, or PGA) is the conjugate acid of 3-phosphoglycerate or glycerate 3-phosphate (GP or G3P). This glycerate is a biochemically significant metabolic intermediate in both glycolysis and the Calvin-Benson cycle. The anion is often termed as PGA when referring to the Calvin-Benson cycle. In the Calvin-Benson cycle, 3-phosphoglycerate is typically the product of the spontaneous scission of an unstable 6-carbon intermediate formed upon CO2 fixation. Thus, two equivalents of 3-phosphoglycerate are produced for each molecule of CO2 that is fixed. In glycolysis, 3-phosphoglycerate is an intermediate following the dephosphorylation (reduction) of 1,3-bisphosphoglycerate.

<span class="mw-page-title-main">Ribose 5-phosphate</span> Chemical compound

Ribose 5-phosphate (R5P) is both a product and an intermediate of the pentose phosphate pathway. The last step of the oxidative reactions in the pentose phosphate pathway is the production of ribulose 5-phosphate. Depending on the body's state, ribulose 5-phosphate can reversibly isomerize to ribose 5-phosphate. Ribulose 5-phosphate can alternatively undergo a series of isomerizations as well as transaldolations and transketolations that result in the production of other pentose phosphates as well as fructose 6-phosphate and glyceraldehyde 3-phosphate.

<span class="mw-page-title-main">Erythrose 4-phosphate</span> Chemical compound

Erythrose 4-phosphate is a phosphate of the simple sugar erythrose. It is an intermediate in the pentose phosphate pathway and the Calvin cycle.

<span class="mw-page-title-main">Xylose metabolism</span>

D-Xylose is a five-carbon aldose that can be catabolized or metabolized into useful products by a variety of organisms.

The enzyme phosphoketolase(EC 4.1.2.9) catalyzes the chemical reactions

<span class="mw-page-title-main">Inborn errors of carbohydrate metabolism</span> Medical condition

Inborn errors of carbohydrate metabolism are inborn error of metabolism that affect the catabolism and anabolism of carbohydrates.

Ribose-5-phosphate isomerase deficiency (RPID) is a rare human disorder caused by mutations in ribose-5-phosphate isomerase, an enzyme of the pentose phosphate pathway. With only four diagnosed patients over a 27-year period, RPI deficiency is the second rarest disease known as of now, being beaten only by Fields Condition affecting two known individuals, Catherine and Kirstie Fields.

Overflow metabolism refers to the seemingly wasteful strategy in which cells incompletely oxidize their growth substrate instead of using the respiratory pathway, even in the presence of oxygen. As a result of employing this metabolic strategy, cells excrete metabolites like lactate, acetate and ethanol. Incomplete oxidation of growth substrates yields less energy than complete oxidation through respiration, and yet overflow metabolism—known as the Warburg effect in the context of cancer and the Crabtree effect in the context of yeast—occurs ubiquitously among fast-growing cells, including bacteria, fungi and mammalian cells.

Aerobic fermentation or aerobic glycolysis is a metabolic process by which cells metabolize sugars via fermentation in the presence of oxygen and occurs through the repression of normal respiratory metabolism. Preference of aerobic fermentation over aerobic respiration is referred to as the Crabtree effect in yeast, and is part of the Warburg effect in tumor cells. While aerobic fermentation does not produce adenosine triphosphate (ATP) in high yield, it allows proliferating cells to convert nutrients such as glucose and glutamine more efficiently into biomass by avoiding unnecessary catabolic oxidation of such nutrients into carbon dioxide, preserving carbon-carbon bonds and promoting anabolism.

References

  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. 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.