Systems and synthetic biology to develop sustainable bioprocesses

Professor Lars Nielsen leads the development of experimental and computational tools to analyse and design complex biological systems. His expertise in metabolic modelling and flux analysis is available nowhere else in Australia – and in few labs across the world. Professor Nielsen’s studies of biological systems as diverse as bacteria, baker's yeast, sugarcane, insects and mammals has attracted industrial partnerships with companies including Dow, Metabolix, Amyris, LanzaTech, Boeing, Virgin Australia and GE. These metabolic engineering partnerships have focussed on developing new ways of producing aviation fuel, various materials and bioactives (antibiotics, biopesticides, monoclonal antibodies). Professor Nielsen is also applying system analysis and design approaches to tissue engineering including novel strategies for generating microtissues for drug screening and using stem cells to produce red and white blood cells for transfusion.

Professor Nielsen has been granted four patents – two in stem cells and another two in metabolic engineering. He is on the Scientific Advisory Board of InSphero (2009–), a Swiss company commercialising microtissue technology originating in the Nielsen laboratory. He is an editorial board member of ACS Synthetic Biology, Metabolic Engineering, Biotechnology Journal, Biotechnology and Bioengineering, Bioprocess & Biosystems Engineering, Metabolic Engineering Communications and Synthetic & Systems Biotechnology. Professor Nielsen formed and chaired the 2005 CRC SIIB Industrial Biotechnology Panel to develop an industrial biotechnology strategy for the Australian sugar industry. He successfully lobbied for the inclusion of Industrial Biotechnology in the Queensland Biotechnology Strategic Plan 2005-2015. Professor Nielsen has received the UQ Foundation Research Excellence Award; and the Australian Institute of Political Science Queensland Young Tall Poppy Award. He was invited to speak at the 2010 Science at the Shine Dome Symposium on Genomics & Mathematics, Canberra; and the Australian Academy of Technical Sciences & Engineering’s National Symposium on Future-Proofing Australia. Professor Nielsen was recently awarded the $8m Novo Nordisk Foundation Laureate Research Grant.

Industry Engagement & Collaborations

  • Amyris collaboration on using synthetic biology for bioproduction, including aviation fuel production
  • Dow collaboration on propionic acid production
  • LanzaTech collaboration on gas fermentation
  • Zoetis collaboration on animal health products
  • CCRM collaboration on production of white blood cells for infection control

Professor Nielsen collaborates with some of the world’s pre-eminent metabolic engineers. A joint project with Professor Sang Yup Lee (KAIST, Korea) enabled several extended mutual visits to explore use of sugar for higher value products. A separate project focused on producing synthetic aviation fuel based on isoprenoids involves Professor Nielsen collaborating with global synthetic biotechnology company Amyris and leading isoprenoid metabolic engineer Professor Jay Keasling, from UC Berkeley. Professor Nielsen has secured $11 million since 2006 from industry through research grants with US, European, Japanese, Korean, New Zealand and Australian companies.

Funding

Professor Nielsen has served as expert advisor to government, research bodies, domestic and major international companies such as Dow Chemical, DuPont and GS Caltex. In the past decade, he has been part of successful research grant applications totalling $56 million, with $31.2 million for his own systems and synthetic biology group at AIBN.

Key Publications

Hefzi et al. (2016) A consensus genome-scale reconstruction of CHO cell metabolism for improved biotherapeutic protein production. Cell Systems 3: 434-443.

Saa PA, Nielsen LK (2016) Construction of feasible and accurate kinetic models of metabolism: A Bayesian approach. Sci Rep 6:29635.

Marcellin E et al. (2016) Low carbon fuels and commodity chemicals from waste gases – Systematic approach to understand energy metabolism in a model acetogen. Green Chemistry 18: 3020-28.

de Oliveira Dal'molin CG, Quek LE, Palfreyman RW, Brumbley SM, Nielsen LK. (2010) A\raGEM - a Genome-Scale Reconstruction of the Primary Metabolic Network in Arabidopsis thaliana. Plant Physiol152, 579–589.

Timmins NE, Palfreyman E, Marturana F, Dietmair S, Luikenga S, Lopez G, Fung YL, Minchinton R, Nielsen LK. (2009) Clinical Scale Ex vivo Manufacture of Neutrophils from Hematopoietic Progenitor Cells. Biotechnol Bioeng104, 832-840.