Jens Nielsen Explained

Jens Nielsen
Nationality:Danish
Workplaces:Chalmers University of Technology, Sweden; BioInnovation Institute, Denmark
Alma Mater:Technical University of Denmark, Denmark
Doctoral Advisor:John Villadsen
Known For:Metabolic engineering, systems biology
Awards:See Awards section

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.

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). Following his studies, he established an independent research group at DTU and was appointed full professor there in 1998. He was Fulbright visiting professor at MIT in 1995–1996. At DTU, he founded and directed the Center for Microbial Biotechnology.

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. 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. 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. 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.

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]

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.[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.

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. He has also developed a number of tools for performing integrative omics analysis, 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.

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.[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.

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[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]

Awards

Academies

Other major honors

External links

Notes and References

  1. https://bioinnovationinstitute.com/ BioInnovation Institute, Denmark
  2. http://www.chalmers.se/en/departments/bio/research/systems-biology Systems and Synthetic Biology, Chalmers
  3. http://www.chalmers.se/en/areas-of-advance/lifescience Area of Advance Life Science Engineering
  4. http://www.chalmers.se/en/departments/bio Department of Biology and Biological Engineering
  5. Web site: Jens Nielsen – Google Scholar Citations .
  6. Web site: Highly Cited Researchers list . 2 February 2020 . https://web.archive.org/web/20171115092422/http://hcr.stateofinnovation.com/ . 15 November 2017 . dead .
  7. Book: Bioreaction Engineering Principles . 10.1007/978-1-4419-9688-6 . 2011 . Villadsen . John . Nielsen . Jens . Lidén . Gunnar . 978-1-4419-9687-9 .
  8. Book: George Stephanopoulos. Aristos A. Aristidou. Jens Nielsen. Metabolic Engineering: Principles and Methodologies. 17 October 1998. Academic Press. 978-0-08-053628-6.
  9. Web site: Jens Nielsen becomes Director of the BioInnovation Institute . Novo Nordisk Fonden . 3 August 2022 . 18 July 2024.
  10. Nielsen J, Keasling JD . Engineering Cellular Metabolism . Cell . 164 . 6 . 1185–97 . 2016 . 26967285 . 10.1016/j.cell.2016.02.004 . 17253851 . free .
  11. Christensen B, Nielsen J . Isotopomer analysis using GC-MS . Metab. Eng. . 1 . 4 . 282–90 . 1999 . 10937821 . 10.1006/mben.1999.0117 .
  12. Nissen TL, Kielland-Brandt MC, Nielsen J, Villadsen J . Optimization of ethanol production in Saccharomyces cerevisiae by metabolic engineering of the ammonium assimilation . Metab. Eng. . 2 . 1 . 69–77 . 2000 . 10935936 . 10.1006/mben.1999.0140 .
  13. Caspeta L, Chen Y, Ghiaci P, Feizi A, Buskov S, Hallström BM, Petranovic D, Nielsen J . Biofuels. Altered sterol composition renders yeast thermotolerant . Science . 346 . 6205 . 75–8 . 2014 . 25278608 . 10.1126/science.1258137 . 206560414 .
  14. Li M, Kildegaard KR, Chen Y, Rodriguez A, Borodina I, Nielsen J . De novo production of resveratrol from glucose or ethanol by engineered Saccharomyces cerevisiae . Metab. Eng. . 32 . 1–11 . 2015 . 26344106 . 10.1016/j.ymben.2015.08.007 . free .
  15. Chen. Yun. Bao. Jichen. Kim. Il-Kwon. Siewers. Verena. Nielsen. Jens. Coupled incremental precursor and co-factor supply improves 3-hydroxypropionic acid production in Saccharomyces cerevisiae. Metabolic Engineering. 22. 2014. 104–109. 1096-7176. 10.1016/j.ymben.2014.01.005. 24502850.
  16. Liu. Lifang. Martínez. José L.. Liu. Zihe. Petranovic. Dina. Nielsen. Jens. Balanced globin protein expression and heme biosynthesis improve production of human hemoglobin in Saccharomyces cerevisiae. Metabolic Engineering. 21. 2014. 9–16. 1096-7176. 10.1016/j.ymben.2013.10.010. 24188961.
  17. Shi S, Valle-Rodríguez JO, Khoomrung S, Siewers V, Nielsen J . Functional expression and characterization of five wax ester synthases in Saccharomyces cerevisiae and their utility for biodiesel production . Biotechnol Biofuels . 5 . 7 . 2012 . 22364438 . 3309958 . 10.1186/1754-6834-5-7 . free .
  18. Zhou. Yongjin J.. Buijs. Nicolaas A.. Zhu. Zhiwei. Gómez. Diego Orol. Boonsombuti. Akarin. Siewers. Verena. Nielsen. Jens. 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. 2016. 15368–15377. 0002-7863. 10.1021/jacs.6b07394. 27753483. 10248013.
  19. Zhou. Yongjin J.. Buijs. Nicolaas A.. Zhu. Zhiwei. Qin. Jiufu. Siewers. Verena. Nielsen. Jens. Production of fatty acid-derived oleochemicals and biofuels by synthetic yeast cell factories. Nature Communications. 7. 2016. 11709. 2041-1723. 10.1038/ncomms11709. 27222209. 4894961. 2016NatCo...711709Z.
  20. Scalcinati G, Partow S, Siewers V, Schalk M, Daviet L, Nielsen J . Combined metabolic engineering of precursor and co-factor supply to increase α-santalene production by Saccharomyces cerevisiae . Microb. Cell Fact. . 11 . 117 . 2012 . 22938570 . 3527295 . 10.1186/1475-2859-11-117 . free .
  21. Tippmann S, Scalcinati G, Siewers V, Nielsen J . Production of farnesene and santalene by Saccharomyces cerevisiae using fed-batch cultivations with RQ-controlled feed . Biotechnol. Bioeng. . 113 . 1 . 72–81 . 2016 . 26108688 . 10.1002/bit.25683 . 32745738 .
  22. Rodriguez A, Kildegaard KR, Li M, Borodina I, Nielsen J . 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 . 2015 . 26292030 . 10.1016/j.ymben.2015.08.003 . free .
  23. Qin. Jiufu. Zhou. Yongjin J.. Krivoruchko. Anastasia. Huang. Mingtao. Liu. Lifang. Khoomrung. Sakda. Siewers. Verena. Jiang. Bo. Nielsen. Jens. Modular pathway rewiring of Saccharomyces cerevisiae enables high-level production of L-ornithine. Nature Communications. 6. 2015. 8224. 2041-1723. 10.1038/ncomms9224. 26345617. 4569842. 2015NatCo...6.8224Q.
  24. Patil. K. R.. Nielsen. J.. Uncovering transcriptional regulation of metabolism by using metabolic network topology. Proceedings of the National Academy of Sciences. 102. 8. 2005. 2685–2689. 0027-8424. 10.1073/pnas.0406811102. 15710883. 549453. 2005PNAS..102.2685P. free.
  25. Gatto F, Nookaew I, Nielsen J . 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 . 2014 . 24550497 . 3948310 . 10.1073/pnas.1319196111 . 2014PNAS..111E.866G . free .
  26. Mardinoglu A, Agren R, Kampf C, Asplund A, Nookaew I, Jacobson P, Walley AJ, Froguel P, Carlsson LM, Uhlen M, Nielsen J . Integration of clinical data with a genome-scale metabolic model of the human adipocyte . Mol. Syst. Biol. . 9 . 649 . 2013 . 23511207 . 3619940 . 10.1038/msb.2013.5 .
  27. Mardinoglu. Adil. Agren. Rasmus. Kampf. Caroline. Asplund. Anna. Uhlen. Mathias. Nielsen. Jens. Genome-scale metabolic modelling of hepatocytes reveals serine deficiency in patients with non-alcoholic fatty liver disease. Nature Communications. 5. 3083. 2014. 2041-1723. 10.1038/ncomms4083. 24419221. 2014NatCo...5.3083M. free.
  28. Agren R, Mardinoglu A, Asplund A, Kampf C, Uhlen M, Nielsen J . Identification of anticancer drugs for hepatocellular carcinoma through personalized genome-scale metabolic modeling . Mol. Syst. Biol. . 10 . 3. 721 . 2014 . 24646661 . 4017677 . 10.1002/msb.145122.
  29. Gatto F, Volpi N, Nilsson H, Nookaew I, Maruzzo M, Roma A, Johansson ME, Stierner U, Lundstam S, Basso U, Nielsen J . Glycosaminoglycan Profiling in Patients' Plasma and Urine Predicts the Occurrence of Metastatic Clear Cell Renal Cell Carcinoma . Cell Rep . 15 . 8 . 1822–36 . 2016 . 27184840 . 10.1016/j.celrep.2016.04.056 . free . 11380/1110792 . free .
  30. Karlsson FH, Fåk F, Nookaew I, Tremaroli V, Fagerberg B, Petranovic D, Bäckhed F, Nielsen J . Symptomatic atherosclerosis is associated with an altered gut metagenome . Nat Commun . 3 . 1245 . 2012 . 23212374 . 3538954 . 10.1038/ncomms2266 . 2012NatCo...3.1245K .
  31. Karlsson FH, Tremaroli V, Nookaew I, Bergström G, Behre CJ, Fagerberg B, Nielsen J, Bäckhed F . Gut metagenome in European women with normal, impaired and diabetic glucose control . Nature . 498 . 7452 . 99–103 . 2013 . 23719380 . 10.1038/nature12198 . 2013Natur.498...99K . 4387028 .
  32. 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 . Quantifying Diet-Induced Metabolic Changes of the Human Gut Microbiome . Cell Metab. . 22 . 2 . 320–31 . 2015 . 26244934 . 10.1016/j.cmet.2015.07.001 . free . 10044/1/28222 . free .
  33. Web site: Billie . Nasrin Sharif . DTU paid tribute to extraordinary efforts . DTU . 4 May 2023 . 19 July 2024.
  34. Web site: Krång . Erik . First Vice President and bioscientist receive the Chalmers Medal . Chalmers tekniska högskola . 1 March 2023 . 19 July 2024.
  35. Web site: Prof. Jens Nielsen won the 2023 International Science and Technology Cooperation Award of the People’s Republic of China . 北京化工大学英文网 . 26 June 2024 . 19 July 2024.
  36. http://www8.nationalacademies.org/onpinews/newsitem.aspx?RecordID=02172010 US National Academy of Engineering
  37. http://academy.asm.org/index.php/fellows-info/fellows-elected-in-2012/332-jens-nielsen American Academy of Microbiology
  38. Web site: 2019 NAS Election. National Academy of Sciences. 30 April 2019.
  39. News: National Academy of Medicine Elects 100 New Members . 9 October 2023 . National Academy of Medicine . 9 October 2023.

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