Jens Nielsen

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 Adjunct Professor at the Technical University of Denmark. He is the most cited researcher in the field of metabolic engineering, and he is the founding president of the International Metabolic Engineering Society. Jens Nielsen is the founder of several biotech companies.

Jens Nielsen
Prof. Jens Nielsen, Chalmers University of Technology, February 2017
NationalityDanish
Alma materTechnical University of Denmark (DTU), Denmark
Known forMetabolic engineering & Systems biology
Awards2002 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, 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 advisorProf. John Villadsen
Websitewww.sysbio.se

Education and academic career

Nielsen has an MSc degree in Chemical Engineering and a PhD degree (1989) in Biochemical Engineering from the Danish Technical University (DTU). He took his dr.techn. degree also from DTU. Following his PhD degree he established his 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 Center for Microbial Biotechnology.

In 2008 he was recruited as Professor and Director to Chalmers University of Technology, Sweden, where he built a research group of more than 60 people.[3] At Chalmers he established the Area of Advance Life Science Engineering,[4] a cross departmental strategic research initiative and was founding Head of the Department of Biology and Biological Engineering,[5] which now encompass about 200 people. Nielsen has published so far more than 700 research papers,[6] co-authored more than 40 books and he is inventor of more than 50 patents. He was identified by Thompson Reuter/Clarivate as a highly cited researcher in 2015-2019,[7] and according to Google Scholar he is the most cited researcher in Metabolic Engineering and top five in Synthetic Biology. He is co-author of several textbooks, and his textbook on Bioreaction Engineering Principles[8] has been published in three editions and his textbook on Metabolic Engineering[9] has been translated to both Chinese and Japanese.

In 2019 Jens 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. BII support start-up companies financially and with business development, and operates an incubator that is open for early stage start-up companies in life science.

Research

Nielsen has been studying and engineering metabolism for almost 30 years. His work has produced, among other, natural rare molecules, antibiotics and biofuels. The scope of this work is to be able to produce valuable compounds in an environmentally friendly and sustainable way that does not depend on petrol processing or extraction from endangered plant species. He is also using his unique approach and methods to study 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 many different 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 many 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 process. Nielsen also worked on improving fermentation processed used for production of industrial enzymes, both using fungi and bacteria.

Metabolic engineering

In connection with his work on improving many classical and new fermentation processed Nielsen developed a number of experimental and computational tools that today is 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, e.g. 1) improved ethanol production by yeast and reduced glycerol formation as a by-product,[12] 2) improved the temperature tolerance of yeast which has enabled ethanol production at elevated temperatures and thereby reduced costs,[13] 3) 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] and ornithine.[23]

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, Penicilium chrysogenum and Pichia pastoris. Nielsen 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] He has also developed methods for performing quantitative metabolome analysis of many microorganisms as well as he has been 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 he 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 very strong biomarker for clear cell renal cell carcinoma,[29] probably the first systems biomarker.

Gut microbiota

Nielsen has also 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 demonstrate 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
  • Novozymes Prize, Novo Nordisk Foundation, Denmark (2016)
  • Gaden Award, American Chemical Society, USA (2016)
  • Norblad-Exstrand Medalj, The Swedish Chemical Society, Sweden (2013)
  • Nature Award for Mentoring, Nature Publishing Group, UK (2012)
  • Charles D. Scott Award 2012, Symposium on Biotechnology for Fuels and Chemicals, USA (2012)
  • Amgen Biochemical Engineering Award, USA (2011)
  • Merck Award for Metabolic Engineering, USA (2004)
  • Villum Kann Rasmussen's Årslegat, Villum Kann Rasmussen Fonden, Denmark (2002)
  • Aksel Tovborg Jensens Legat, Bjerrum-Brøndsted-Lang Lecture, Carlsberg Foundation, Denmark (2001)
  • STVFs Jubilæumspris, Statens Teknisk Videnskabelige Forskningsråd, Denmark (1996)
  • Ulrik Brinch og Hustru Marie Brinch's legat, Denmark (1994)
  • Direktør Gorm Petersen's Mindelegat, Denmark (1989)

Academies

Other major honors
  • Zhang Dayu Lectureship, Dalian Institute for Chemical Physics, Chinese Academy of Sciences, China (2015)
  • Honorary Professor, Beijing University of Chemical Technology, Beijing, China (2014)
  • William Chalmers Lecture, Chalmers University of Technology, Sweden (2014)
  • Appointed as Wallenberg Scholar, Sweden (2010)
  • Hough Memorial Lecture, Birmingham University, UK (2004)
  • Sunner Memorial Lecture, Lund University, Sweden (2002)
  • Fulbright Fellow, USA (1995)

Companies

Nielsen founded Fluxome A/S that raised more than M20EUR in venture capital. This company metabolically engineered yeast for production of resveratrol and used this yeast for commercial production of this compound. This process was acquired by the company Evolva. Nielsen has founded several other biotech companies, including Metabogen AB, Biopetrolia AB and Elypta AB, and he has served in the scientific advisory board of a range of different biotech companies in the US and Europe.

Personal

Nielsen is originally from Horsens in Denmark.

References
  1. BioInnovation Institute, Denmark
  2. Systems and Synthetic Biology, Chalmers
  3. sysbio.se group website
  4. Area of Advance Life Science Engineering
  5. Department of Biology and Biological Engineering
  6. "Jens Nielsen - Google Scholar Citations".
  7. "Highly Cited Researchers list". Archived from the original on 2017-11-15. Retrieved 2020-02-02.
  8. John Villadsen; Jens Nielsen; Gunnar Lidén. Bioreaction Engineering Principles. Springer.
  9. George Stephanopoulos; Aristos A. Aristidou; Jens Nielsen (17 October 1998). Metabolic Engineering: Principles and Methodologies. Academic Press. ISBN 978-0-08-053628-6.
  10. 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.
  11. Christensen B, Nielsen J (1999). "Isotopomer analysis using GC-MS". Metab. Eng. 1 (4): 282–90. doi:10.1006/mben.1999.0117. PMID 10937821.
  12. 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.
  13. 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.
  14. 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.
  15. 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.
  16. 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.
  17. 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.
  18. 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.
  19. 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.
  20. 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.
  21. 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.
  22. 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.
  23. 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.
  24. 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.
  25. 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.
  26. 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.
  27. 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.
  28. 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.
  29. 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.
  30. 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.
  31. 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.
  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 (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.
  33. "2019 NAS Election". National Academy of Sciences. April 30, 2019.
  34. American Academy of Microbiology
  35. US National Academy of Engineering
  • Professor Jens Nielsen was ranked as the fourth most cited researcher in Europe in the field of mycology.
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