Markus Ralser | |
---|---|
Born | 3 April 1980 |
Nationality | Italian |
Alma mater | University of Salzburg Max Planck Institute for Molecular Genetics University of Cambridge |
Awards | Wellcome Beit Prize EMBO Gold Medal |
Scientific career | |
Fields | Metabolism |
Institutions | University of Cambridge Francis Crick Institute Charité University of Oxford |
Website | ralser |
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.
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.
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:
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]
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.
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.
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.
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.
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).
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.
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.
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.
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.
Erythrose 4-phosphate is a phosphate of the simple sugar erythrose. It is an intermediate in the pentose phosphate pathway and the Calvin cycle.
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
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.
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