Jens Nielsen | |
---|---|
Nationality | Danish |
Alma mater | Technical University of Denmark, Denmark |
Known for | Metabolic engineering, systems biology |
Awards | See Awards section |
Scientific career | |
Institutions | Chalmers University of Technology, Sweden; BioInnovation Institute, Denmark |
Doctoral advisor | John Villadsen |
Jens Nielsen is the CEO of BioInnovation Institute, [1] Copenhagen, Denmark, and professor of systems biology [2] at Chalmers University of Technology, Gothenburg, Sweden. He is also an adjunct professor at the Danish Technical University and the University of Copenhagen. Nielsen is the most cited researcher in the field of metabolic engineering, and he is the most cited researcher in Biology and Biochemistry in Sweden and Denmark (top 5 in Europe). He is the only foreign member of all three academies in the US (Science, Engineering and Medicine) and he is also foreign member of the Chinese Academy of Engineering. He was the founding president of the International Metabolic Engineering Society. He has additionally founded several biotech companies.
Jens Nielsen obtained his high school degree from Horsens Statsskole in 1981, and his MSc in chemical engineering (1986) and PhD in biochemical engineering (1989) from the Danish Technical University (DTU).[ citation needed ] Following his studies, he established an independent research group at DTU and was appointed full professor there in 1998.[ citation needed ] He was Fulbright visiting professor at MIT in 1995–1996.[ citation needed ] At DTU, he founded and directed the Center for Microbial Biotechnology.[ citation needed ]
In 2008, he was recruited as professor and director at Chalmers University of Technology, Sweden, where he built a research group of more than sixty people.[ citation needed ] At Chalmers, he established the Area of Advance Life Science Engineering, [3] a cross-departmental strategic research initiative, and was founding head of the Department of Biology and Biological Engineering, [4] which now both encompass about 200 people. Nielsen has published over 850 research papers, [5] co-authored more than forty books, and is the holder of more than fifty patents.[ citation needed ] He was identified by Thomson Reuters/Clarivate as a highly cited researcher in 2015–2023, [6] and according to Google Scholar, he is the most cited researcher in metabolic engineering, industrial biotechnology, and among the top five in synthetic biology.[ citation needed ] He is co-author of several textbooks, and his textbook on bioreaction engineering principles [7] has been published in three editions. His textbook on metabolic engineering [8] has been translated into Chinese and Japanese.[ citation needed ]
In 2019, Nielsen was recruited as CEO of BioInnovation Institute (BII), an initiative by the Novo Nordisk Foundation to support innovation and translation of science for use in society. [9]
Nielsen has been studying and engineering metabolism for close to thirty years. His work has produced natural rare molecules, antibiotics, and biofuels. He also studies metabolism in humans, with specific interest in metabolic diseases such as type 2 diabetes, obesity, cardiovascular disease, and various cancers.
This section of a biography of a living person does not include any references or sources .(November 2022) |
Nielsen has worked on studying and improving various industrial biotechnological processes. Initially, he worked on physiological characterization of the filamentous fungus Penicillium chrysogenum that is used for penicillin production. This resulted in continued work, together with the Dutch company DSM, on development of a novel process for production of adipoyl-7-ADCA, a precursor for cephalexin. He also worked on characterization of other fermentation processes used for antibiotics production, and through the use of his experimental and modelling techniques, he assisted several companies with improving their production processes. Nielsen has also worked on improving fermentation processes used for production of industrial enzymes, both using fungi and bacteria.
In connection with his work on improving classical and new fermentation processes, Nielsen developed a number of experimental and computational tools that today are the foundation for metabolic engineering—the directed genetic modification of cells with the objective of improving the phenotype. [10] He was the first to use gas-chromatography mass-spectrometry (GC-MS) as an experimental tool for measurement of C13-labelled metabolites, with the objective to perform flux analysis. [11] Through metabolic engineering, Nielsen has developed and improved a number of biotechnological processes, such as improving ethanol production by yeast and reducing glycerol formation as a by-product; [12] improving the temperature tolerance of yeast, which has enabled ethanol production at elevated temperatures and thereby reduced costs; [13] production of a range of different chemicals using engineered yeast, such as resveratrol, [14] 3-hydroxypropionic acid, [15] human haemoglobin, [16] fatty acid ethyl esters, [17] short-chain fatty acids, alkanes, [18] fatty alcohols, [19] santalene, [20] farnesene, [21] coumaric acid, [22] ornithine, [23] and spermidine.
Nielsen has pioneered the development of systems biology tools for industrial microorganisms. He has developed genome-scale metabolic models (GEMs) for many important industrial microorganisms, including yeast ( Saccharomyces cerevisiae ), Lactococcus lactis, Streptomyces coelicolor, Aspergillus oryzae , Aspergillus niger , Penicillium chrysogenum, and Pichia pastoris.[ citation needed ] He has also developed a number of tools for performing integrative omics analysis,[ clarification needed ] and he was the first to demonstrate how transcriptome data could be integrated in the context of GEMs in order to gain insight into co-regulation. [24] Nielsen has also developed methods for performing quantitative metabolome analysis of many microorganisms as well as being involved in genome-sequencing of several key industrial microorganisms.[ citation needed ]
Using his systems biology toolbox developed for microorganisms, Nielsen initiated work on human metabolism. In connection with this, he developed a comprehensive genome-scale metabolic model for human cells and was the first to use a human GEM to illustrate the metabolic heterogeneity of cancer metabolism. [25] His work on human metabolism has involved studies of different diseases, such as obesity, [26] NAFLD and NASH, [27] and hepatocellular carcinoma. [28] Nielsen further used human GEMs to identify that combined measurements of several glycosaminoglycans can be used as a strong biomarker for clear cell renal cell carcinoma, [29] probably the first systems biomarker.
Nielsen has used his systems biology competence to study the metabolism of the gut microbiota. He was involved in early studies on using metagenome sequencing for characterization of the gut microbiota and demonstrating that variations are associated with cardiovascular disease [30] and type 2 diabetes. [31] He also used his advanced metabolic modelling skills to gain further functional insight into how the gut microbiota impacts changes in plasma metabolomics in response to dietary changes. [32]
This section of a biography of a living person does not include any references or sources .(February 2022) |
This section of a biography of a living person needs additional citations for verification .(November 2022) |
This section of a biography of a living person does not include any references or sources .(November 2022) |
Yeasts are eukaryotic, single-celled microorganisms classified as members of the fungus kingdom. The first yeast originated hundreds of millions of years ago, and at least 1,500 species are currently recognized. They are estimated to constitute 1% of all described fungal species.
Succinic acid is a dicarboxylic acid with the chemical formula (CH2)2(CO2H)2. In living organisms, succinic acid takes the form of an anion, succinate, which has multiple biological roles as a metabolic intermediate being converted into fumarate by the enzyme succinate dehydrogenase in complex 2 of the electron transport chain which is involved in making ATP, and as a signaling molecule reflecting the cellular metabolic state.
Saccharomyces cerevisiae is a species of yeast. The species has been instrumental in winemaking, baking, and brewing since ancient times. It is believed to have been originally isolated from the skin of grapes. It is one of the most intensively studied eukaryotic model organisms in molecular and cell biology, much like Escherichia coli as the model bacterium. It is the microorganism which causes many common types of fermentation. S. cerevisiae cells are round to ovoid, 5–10 μm in diameter. It reproduces by budding.
Metabolic engineering is the practice of optimizing genetic and regulatory processes within cells to increase the cell's production of a certain substance. These processes are chemical networks that use a series of biochemical reactions and enzymes that allow cells to convert raw materials into molecules necessary for the cell's survival. Metabolic engineering specifically seeks to mathematically model these networks, calculate a yield of useful products, and pin point parts of the network that constrain the production of these products. Genetic engineering techniques can then be used to modify the network in order to relieve these constraints. Once again this modified network can be modeled to calculate the new product yield.
The word metagenics uses the prefix meta and the suffix gen. Literally, it means "the creation of something which creates". In the context of biotechnology, metagenics is the practice of engineering organisms to create a specific enzyme, protein, or other biochemicals from simpler starting materials. The genetic engineering of E. coli with the specific task of producing human insulin from starting amino acids is an example. E. coli has also been engineered to digest plant biomass and use it to produce hydrocarbons in order to synthesize biofuels. The applications of metagenics on E. coli also include higher alcohols, fatty-acid based chemicals and terpenes.
Jay D. Keasling is a professor of chemical engineering and bioengineering at the University of California, Berkeley. He is also associate laboratory director for biosciences at the Lawrence Berkeley National Laboratory and chief executive officer of the Joint BioEnergy Institute. He is considered one of the foremost authorities in synthetic biology, especially in the field of metabolic engineering.
The Crabtree effect, named after the English biochemist Herbert Grace Crabtree, describes the phenomenon whereby the yeast, Saccharomyces cerevisiae, produces ethanol (alcohol) in aerobic conditions at high external glucose concentrations rather than producing biomass via the tricarboxylic acid (TCA) cycle, the usual process occurring aerobically in most yeasts e.g. Kluyveromyces spp. This phenomenon is observed in most species of the Saccharomyces, Schizosaccharomyces, Debaryomyces, Brettanomyces, Torulopsis, Nematospora, and Nadsonia genera. Increasing concentrations of glucose accelerates glycolysis which results in the production of appreciable amounts of ATP through substrate-level phosphorylation. This reduces the need of oxidative phosphorylation done by the TCA cycle via the electron transport chain and therefore decreases oxygen consumption. The phenomenon is believed to have evolved as a competition mechanism around the time when the first fruits on Earth fell from the trees. The Crabtree effect works by repressing respiration by the fermentation pathway, dependent on the substrate.
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
In enzymology, glucosamine-phosphate N-acetyltransferase (GNA) is an enzyme that catalyzes the transfer of an acetyl group from acetyl-CoA to the primary amine in glucosamide-6-phosphate, generating a free CoA and N-acetyl-D-glucosamine-6-phosphate.
Mucor indicus is among the most important members of zygomycetes fungi. This dimorphic fungus is capable of production of several valuable products. Some strains of the fungus have been isolated from the traditional Indonesian food tempeh. M. indicus is nowadays used for production of several homemade food and beverages especially in Asia. This has also been successfully used as a safe nutritional source for fish and rat. The fungus is generally regarded as safe though there are few reports claiming that this is a pathogenic fungus.
Cofactor engineering, a subset of metabolic engineering, is defined as the manipulation of the use of cofactors in an organism’s metabolic pathways. In cofactor engineering, the concentrations of cofactors are changed in order to maximize or minimize metabolic fluxes. This type of engineering can be used to optimize the production of a metabolite product or to increase the efficiency of a metabolic network. The use of engineering single celled organisms to create lucrative chemicals from cheap raw materials is growing, and cofactor engineering can play a crucial role in maximizing production. The field has gained more popularity in the past decade and has several practical applications in chemical manufacturing, bioengineering and pharmaceutical industries.
Bernhard Örn Pálsson is the Galletti Professor of Bioengineering and an adjunct professor of Medicine at the University of California, San Diego.
Strictosidine is a natural chemical compound and is classified as a glucoalkaloid and a vinca alkaloid. It is formed by the Pictet–Spengler condensation reaction of tryptamine with secologanin, catalyzed by the enzyme strictosidine synthase. Thousands of strictosidine derivatives are sometimes referred to by the broad phrase of monoterpene indole alkaloids. Strictosidine is an intermediate in the biosynthesis of numerous pharmaceutically valuable metabolites including quinine, camptothecin, ajmalicine, serpentine, vinblastine, vincristine and mitragynine.
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.
Robert L. Last is a plant biochemical genomicist who studies metabolic processes that protect plants from the environment and produce products important for animal and human nutrition. His research has covered (1) production and breakdown of essential amino acids, (2) the synthesis and protective roles of Vitamin C and Vitamin E (tocopherols) as well as identification of mechanisms that protect photosystem II from damage, and (3) synthesis and biological functions of plant protective specialized metabolites. Four central questions are: (i) how are leaf and seed amino acids levels regulated, (ii.) what mechanisms protect and repair photosystem II from stress-induced damage, (iii.) how do plants produce protective metabolites in their glandular secreting trichomes (iv.) and what are the evolutionary mechanisms that contribute to the tremendous diversity of specialized metabolites that protect plants from insects and pathogens and are used as therapeutic agents.
Ram Rajasekharan is an Indian plant biologist, food technologist and a former director of the Central Food Technological Research Institute (CFTRI), a constituent laboratory of the Council of Scientific and Industrial Research. Known for his studies on plant lipid metabolism, Rajasekharan is a former professor of eminence at the Indian Institute of Science and an elected fellow of all the three major Indian science academies namely Indian Academy of Sciences, National Academy of Sciences, India and Indian National Science Academy as well as the National Academy of Agricultural Sciences. The Department of Biotechnology of the Government of India awarded him the National Bioscience Award for Career Development, one of the highest Indian science awards, for his contributions to biosciences in 2001.
Matthias Heinemann is a professor of molecular systems biology at the University of Groningen. Heinemann leads an interdisciplinary lab of approximately 12 graduate students and post-doctoral scholars. Until 2019, he served as the chairman of the Groningen Biomolecular Sciences and Biotechnology Institute, was a board member of the Dutch Origins Center and the coordinator of EU ITN project MetaRNA. Heinemann is a member of the Faculty of 1000.
Eckhard Boles is a German microbiologist and biotechnologist. Since 2002 he is professor of microbiology at the Goethe University Frankfurt with a focus on the physiology and genetics of lower eukaryotes. He works mainly on the optimization of yeasts for industrial biotechnology.
The arginine-glycine or arginine-glycine-glycine (RG/RGG) motif is a repeating amino acid sequence motif commonly found in RNA-binding proteins (RBPs). RGG regions in proteins are defined as two or more RG/RGG sequences within a stretch of 30 amino acids. Initially named the RGG box, it confers a protein with the ability to bind double-stranded mRNA molecules. The RGG motif has been observed in proteins from at least 12 animal species, including humans.