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Jens Nielsen

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Jens Nielsen
middle-aged white male with short brown hair, wearing glasses, a dark red patterned tie, and a blue-and-white checkered shirt, grinning at camera
Nielsen in 2017
NationalityDanish
Alma materTechnical University of Denmark, Denmark
Known forMetabolic 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
InstitutionsChalmers University of Technology, Sweden; BioInnovation Institute, Denmark
Doctoral advisorJohn 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.

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

  • Direktør Gorm Petersen's Mindelegat, Denmark (1989)
  • Ulrik Brinch og Hustru Marie Brinch's legat, Denmark (1994)
  • STVFs Jubilæumspris, Statens Teknisk Videnskabelige Forskningsråd, Denmark (1996)
  • Aksel Tovborg Jensens Legat, Bjerrum-Brøndsted-Lang Lecture, Carlsberg Foundation, Denmark (2001)
  • Villum Kann Rasmussen's Årslegat, Villum Kann Rasmussen Fonden, Denmark (2002)
  • Merck Award for Metabolic Engineering, USA (2004)
  • Amgen Biochemical Engineering Award, USA (2011)
  • Nature Award for Mentoring, Nature Publishing Group, UK (2012)
  • Charles D. Scott Award 2012, Symposium on Biotechnology for Fuels and Chemicals, USA (2012)
  • Norblad-Exstrand Medalj, Swedish Chemical Society, Sweden (2013)
  • Novozymes Prize, Novo Nordisk Foundation, Denmark (2016)
  • Gaden Award, American Chemical Society, USA (2016)
  • Gold Medal, Royal Swedish Academy of Engineering Sciences, Sweden (2017)
  • Eric and Sheila Samson Prime Ministers Prize for Innovation in Alternative Fuels for Transportation, Fuels, and Smart Mobility Initiative, Israel (2017)
  • ENI Award, Italy (2017)
  • James E. Bailey Award, American Institute for Chemical Engineering, USA (2019)
  • Arvid Carlssons Award, Sahlgrenska Science Park, Sweden (2019)
  • Emil Chr. Hansen's Gold Medal for Microbiological Research, Denmark (2019)
  • Gregory Stephanopoulos Award for Metabolic Engineering, IMES, USA (2020)
  • The Chinese Government Friendship Award, China (2021)

Academies

Other major honors

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. 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. 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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