Jens Nielsen

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Jens Nielsen
Prof. Jens Nielsen, Chalmers University of Technology, February 2017.jpg
Nielsen in 2017
NationalityDanish
Alma mater Technical University of Denmark, Denmark
Known for Metabolic engineering, systems biology
Awards
  • 2002 Villum Kann Rasmussen's Årslegat
  • 2004 Merck Award for Metabolic Engineering
  • 2011 Amgen Biochemical Engineering Award
  • 2012 Nature Mentor Award
  • 2016 Novozymes Prize
  • 2017 ENI Award
  • 2017 Gold Medal IVA
  • 2017 Eric and Sheila Samson Prime Ministers Prize for Innovation in Alternative Fuels for Transportation
  • 2019 Emil Chr. Hansen's Gold Medal
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 Technical University of Denmark. Nielsen is the most cited researcher in the field of metabolic engineering, and he is the founding president of the International Metabolic Engineering Society. He has additionally founded several biotech companies.

Contents

Education and academic career

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 700 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 2015–2021, [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.[ citation needed ]

Research

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.

Industrial microbiology

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.

Metabolic engineering

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. [9] 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. [10] 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; [11] improving the temperature tolerance of yeast, which has enabled ethanol production at elevated temperatures and thereby reduced costs; [12] production of a range of different chemicals using engineered yeast, such as resveratrol, [13] 3-hydroxypropionic acid, [14] human haemoglobin, [15] fatty acid ethyl esters, [16] short-chain fatty acids, alkanes, [17] fatty alcohols, [18] santalene, [19] farnesene, [20] coumaric acid, [21] ornithine, [22] and spermidine.

Systems biology of industrial microorganisms

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. [23] 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 ]

Human metabolism

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. [24] His work on human metabolism has involved studies of different diseases, such as obesity, [25] NAFLD and NASH, [26] and hepatocellular carcinoma. [27] 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, [28] probably the first systems biomarker.

Gut microbiota

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 [29] and type 2 diabetes. [30] 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. [31]

Awards

Academies

Other major honors

Related Research Articles

<span class="mw-page-title-main">Metabolism</span> Set of chemical reactions in organisms

Metabolism is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cellular processes; the conversion of food to building blocks of proteins, lipids, nucleic acids, and some carbohydrates; and the elimination of metabolic wastes. These enzyme-catalyzed reactions allow organisms to grow and reproduce, maintain their structures, and respond to their environments. The word metabolism can also refer to the sum of all chemical reactions that occur in living organisms, including digestion and the transportation of substances into and between different cells, in which case the above described set of reactions within the cells is called intermediary metabolism.

<span class="mw-page-title-main">Yeast</span> Informal group of fungi

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.

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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 behind the most common type of fermentation. S. cerevisiae cells are round to ovoid, 5–10 μm in diameter. It reproduces by budding.

<span class="mw-page-title-main">Enoyl CoA isomerase</span>

Enoyl-CoA-(∆) isomerase (EC 5.3.3.8, also known as dodecenoyl-CoA- isomerase, 3,2-trans-enoyl-CoA isomerase, ∆3 ,∆2 -enoyl-CoA isomerase, or acetylene-allene isomerase, is an enzyme that catalyzes the conversion of cis- or trans-double bonds of coenzyme A bound fatty acids at gamma-carbon to trans double bonds at beta-carbon as below:

<span class="mw-page-title-main">Metabolic engineering</span>

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.

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

Mandelic acid is an aromatic alpha hydroxy acid with the molecular formula C6H5CH(OH)CO2H. It is a white crystalline solid that is soluble in water and polar organic solvents. It is a useful precursor to various drugs. The molecule is chiral. The racemic mixture is known as paramandelic acid.

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<span class="mw-page-title-main">Metabolic flux analysis</span> Experimental fluxomics technique

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

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

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<span class="mw-page-title-main">Glucosamine-phosphate N-acetyltransferase</span>

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.

<span class="mw-page-title-main">Cofactor engineering</span> Modification of use and function of cofactors in an organisms metabolic pathways

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References

  1. ↑ BioInnovation Institute, Denmark
  2. ↑ Systems and Synthetic Biology, Chalmers
  3. ↑ Area of Advance Life Science Engineering
  4. ↑ Department of Biology and Biological Engineering
  5. ↑ "Jens Nielsen – Google Scholar Citations".
  6. ↑ "Highly Cited Researchers list". Archived from the original on 15 November 2017. Retrieved 2 February 2020.
  7. ↑ John Villadsen; Jens Nielsen; Gunnar Lidén. Bioreaction Engineering Principles. Springer.
  8. ↑ George Stephanopoulos; Aristos A. Aristidou; Jens Nielsen (17 October 1998). Metabolic Engineering: Principles and Methodologies. Academic Press. ISBN   978-0-08-053628-6.
  9. ↑ Nielsen J, Keasling JD (2016). "Engineering Cellular Metabolism" (PDF). Cell. 164 (6): 1185–97. doi: 10.1016/j.cell.2016.02.004 . PMID   26967285. S2CID   17253851.
  10. ↑ Christensen B, Nielsen J (1999). "Isotopomer analysis using GC-MS". Metab. Eng. 1 (4): 282–90. doi:10.1006/mben.1999.0117. PMID   10937821.
  11. ↑ Nissen TL, Kielland-Brandt MC, Nielsen J, Villadsen J (2000). "Optimization of ethanol production in Saccharomyces cerevisiae by metabolic engineering of the ammonium assimilation". Metab. Eng. 2 (1): 69–77. doi:10.1006/mben.1999.0140. PMID   10935936.
  12. ↑ Caspeta L, Chen Y, Ghiaci P, Feizi A, Buskov S, Hallström BM, Petranovic D, Nielsen J (2014). "Biofuels. Altered sterol composition renders yeast thermotolerant". Science. 346 (6205): 75–8. doi:10.1126/science.1258137. PMID   25278608. S2CID   206560414.
  13. ↑ Li M, Kildegaard KR, Chen Y, Rodriguez A, Borodina I, Nielsen J (2015). "De novo production of resveratrol from glucose or ethanol by engineered Saccharomyces cerevisiae". Metab. Eng. 32: 1–11. doi: 10.1016/j.ymben.2015.08.007 . PMID   26344106.
  14. ↑ Chen, Yun; Bao, Jichen; Kim, Il-Kwon; Siewers, Verena; Nielsen, Jens (2014). "Coupled incremental precursor and co-factor supply improves 3-hydroxypropionic acid production in Saccharomyces cerevisiae". Metabolic Engineering. 22: 104–109. doi:10.1016/j.ymben.2014.01.005. ISSN   1096-7176. PMID   24502850.
  15. ↑ Liu, Lifang; Martínez, José L.; Liu, Zihe; Petranovic, Dina; Nielsen, Jens (2014). "Balanced globin protein expression and heme biosynthesis improve production of human hemoglobin in Saccharomyces cerevisiae". Metabolic Engineering. 21: 9–16. doi:10.1016/j.ymben.2013.10.010. ISSN   1096-7176. PMID   24188961.
  16. ↑ Shi S, Valle-Rodríguez JO, Khoomrung S, Siewers V, Nielsen J (2012). "Functional expression and characterization of five wax ester synthases in Saccharomyces cerevisiae and their utility for biodiesel production". Biotechnol Biofuels. 5: 7. doi: 10.1186/1754-6834-5-7 . PMC   3309958 . PMID   22364438.
  17. ↑ Zhou, Yongjin J.; Buijs, Nicolaas A.; Zhu, Zhiwei; Gómez, Diego Orol; Boonsombuti, Akarin; Siewers, Verena; Nielsen, Jens (2016). "Harnessing Yeast Peroxisomes for Biosynthesis of Fatty-Acid-Derived Biofuels and Chemicals with Relieved Side-Pathway Competition". Journal of the American Chemical Society. 138 (47): 15368–15377. doi:10.1021/jacs.6b07394. ISSN   0002-7863. PMID   27753483. S2CID   10248013.
  18. ↑ Zhou, Yongjin J.; Buijs, Nicolaas A.; Zhu, Zhiwei; Qin, Jiufu; Siewers, Verena; Nielsen, Jens (2016). "Production of fatty acid-derived oleochemicals and biofuels by synthetic yeast cell factories". Nature Communications. 7: 11709. Bibcode:2016NatCo...711709Z. doi:10.1038/ncomms11709. ISSN   2041-1723. PMC   4894961 . PMID   27222209.
  19. ↑ Scalcinati G, Partow S, Siewers V, Schalk M, Daviet L, Nielsen J (2012). "Combined metabolic engineering of precursor and co-factor supply to increase α-santalene production by Saccharomyces cerevisiae". Microb. Cell Fact. 11: 117. doi: 10.1186/1475-2859-11-117 . PMC   3527295 . PMID   22938570.
  20. ↑ Tippmann S, Scalcinati G, Siewers V, Nielsen J (2016). "Production of farnesene and santalene by Saccharomyces cerevisiae using fed-batch cultivations with RQ-controlled feed". Biotechnol. Bioeng. 113 (1): 72–81. doi:10.1002/bit.25683. PMID   26108688. S2CID   32745738.
  21. ↑ Rodriguez A, Kildegaard KR, Li M, Borodina I, Nielsen J (2015). "Establishment of a yeast platform strain for production of p-coumaric acid through metabolic engineering of aromatic amino acid biosynthesis". Metab. Eng. 31: 181–8. doi: 10.1016/j.ymben.2015.08.003 . PMID   26292030.
  22. ↑ Qin, Jiufu; Zhou, Yongjin J.; Krivoruchko, Anastasia; Huang, Mingtao; Liu, Lifang; Khoomrung, Sakda; Siewers, Verena; Jiang, Bo; Nielsen, Jens (2015). "Modular pathway rewiring of Saccharomyces cerevisiae enables high-level production of L-ornithine". Nature Communications. 6: 8224. Bibcode:2015NatCo...6.8224Q. doi:10.1038/ncomms9224. ISSN   2041-1723. PMC   4569842 . PMID   26345617.
  23. ↑ Patil, K. R.; Nielsen, J. (2005). "Uncovering transcriptional regulation of metabolism by using metabolic network topology". Proceedings of the National Academy of Sciences. 102 (8): 2685–2689. Bibcode:2005PNAS..102.2685P. doi: 10.1073/pnas.0406811102 . ISSN   0027-8424. PMC   549453 . PMID   15710883.
  24. ↑ Gatto F, Nookaew I, Nielsen J (2014). "Chromosome 3p loss of heterozygosity is associated with a unique metabolic network in clear cell renal carcinoma". Proc. Natl. Acad. Sci. U.S.A. 111 (9): E866–75. Bibcode:2014PNAS..111E.866G. doi: 10.1073/pnas.1319196111 . PMC   3948310 . PMID   24550497.
  25. ↑ Mardinoglu A, Agren R, Kampf C, Asplund A, Nookaew I, Jacobson P, Walley AJ, Froguel P, Carlsson LM, Uhlen M, Nielsen J (2013). "Integration of clinical data with a genome-scale metabolic model of the human adipocyte". Mol. Syst. Biol. 9: 649. doi:10.1038/msb.2013.5. PMC   3619940 . PMID   23511207.
  26. ↑ Mardinoglu, Adil; Agren, Rasmus; Kampf, Caroline; Asplund, Anna; Uhlen, Mathias; Nielsen, Jens (2014). "Genome-scale metabolic modelling of hepatocytes reveals serine deficiency in patients with non-alcoholic fatty liver disease". Nature Communications. 5: 3083. Bibcode:2014NatCo...5.3083M. doi: 10.1038/ncomms4083 . ISSN   2041-1723. PMID   24419221.
  27. ↑ Agren R, Mardinoglu A, Asplund A, Kampf C, Uhlen M, Nielsen J (2014). "Identification of anticancer drugs for hepatocellular carcinoma through personalized genome-scale metabolic modeling". Mol. Syst. Biol. 10 (3): 721. doi:10.1002/msb.145122. PMC   4017677 . PMID   24646661.
  28. ↑ Gatto F, Volpi N, Nilsson H, Nookaew I, Maruzzo M, Roma A, Johansson ME, Stierner U, Lundstam S, Basso U, Nielsen J (2016). "Glycosaminoglycan Profiling in Patients' Plasma and Urine Predicts the Occurrence of Metastatic Clear Cell Renal Cell Carcinoma". Cell Rep. 15 (8): 1822–36. doi: 10.1016/j.celrep.2016.04.056 . hdl: 11380/1110792 . PMID   27184840.
  29. ↑ Karlsson FH, Fåk F, Nookaew I, Tremaroli V, Fagerberg B, Petranovic D, Bäckhed F, Nielsen J (2012). "Symptomatic atherosclerosis is associated with an altered gut metagenome". Nat Commun. 3: 1245. Bibcode:2012NatCo...3.1245K. doi:10.1038/ncomms2266. PMC   3538954 . PMID   23212374.
  30. ↑ Karlsson FH, Tremaroli V, Nookaew I, Bergström G, Behre CJ, Fagerberg B, Nielsen J, Bäckhed F (2013). "Gut metagenome in European women with normal, impaired and diabetic glucose control". Nature. 498 (7452): 99–103. Bibcode:2013Natur.498...99K. doi:10.1038/nature12198. PMID   23719380. S2CID   4387028.
  31. ↑ Shoaie S, Ghaffari P, Kovatcheva-Datchary P, Mardinoglu A, Sen P, Pujos-Guillot E, de Wouters T, Juste C, Rizkalla S, Chilloux J, Hoyles L, Nicholson JK, Dore J, Dumas ME, Clement K, Bäckhed F, Nielsen J (2015). "Quantifying Diet-Induced Metabolic Changes of the Human Gut Microbiome". Cell Metab. 22 (2): 320–31. doi: 10.1016/j.cmet.2015.07.001 . hdl: 10044/1/28222 . PMID   26244934.
  32. ↑ US National Academy of Engineering
  33. ↑ American Academy of Microbiology
  34. ↑ "2019 NAS Election". National Academy of Sciences. 30 April 2019.
  35. ↑ "National Academy of Medicine Elects 100 New Members". National Academy of Medicine. 9 October 2023. Retrieved 9 October 2023.
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