Nielsen Group

The Nielsen Group, led by Senior Group Leader Professor Lars Nielsen, uses systems biology – that is, systems science, modelling and simulation – to integrate data streams and generate knowledge. As applied systems biologists or biotechnologists, they do more than develop tools for better understanding (analysis); they use these tools to design products and processes for human benefit (synthesis). The science is moving from crude retrofitting of living systems with a single or few genes using genetic engineering, to purposeful reengineering of living systems using systems and synthetic biology.

Drawing on a common core of expertise in genome scale metabolic modelling and the full range of ‘omics technologies, the Group studies a diverse range of biological systems, including model and industrial microbes, animals cells, plants and increasingly complex ecosystems.

Research Highlights

Professor Lars Nielsen

Senior Group Leader

Nielsen Group

Researchers

Dr Cristiana Dal'Molin

Lecturer

Chemical Engineering
Affiliate Research Fellow

Australian Institute for Bioengineering and Nanotechnology
Dr Robin Palfreyman

Research Fellow

Nielsen Group
Dr Manuel Plan

Analytical Officer

Australian Institute for Bioengineering and Nanotechnology
Ms Terra Stark

Research Assistant

Australian Institute for Bioengineering and Nanotechnology

Students

Pedro Saa Higuera

PhD student

Nielsen Group
Miss Kanupriya Tiwari

We run the Queenlsand Node of Metabolomics Australia. The facility is available to the public.
Visit the Metabolomics Australia page for further details.

Genome Databases

We have developed Biocyc databases and genome scale models for most of the organisms we work with.

Mouse GEM - SBML for mouse genome scale model

Quek L-E, Nielsen LK (2008) On the reconstruction of the Mus musculus genome-scale metabolic network model. Genome Informatics 21:89-100.

AraFlux - A Matlab Toolbox for performing flux analysis using AraGEM genome scale model

de Oliveira Dal'molin CG, Quek LE, Palfreyman RW, Brumbley SM, Nielsen LK (2010) AraGEM - a Genome-Scale Reconstruction of the Primary Metabolic Network in Arabidopsis thaliana. Plant Physiol. 152: 579–589. PMID: 20044452.

AraGEM COBRA - AraGEM SBML file for use with COBRA Toolbox in Matlab

Mammalian MFA - Matlab files for mammalian cell culture MFA using reduced Mouse GEM

Quek L-E, Dietmair S; Kr?mer JO, Nielsen LK (2010) Metabolic flux analysis in mammalian cell culture. Metabolic Engineering 12: 161-171. PMID: 19833223.

C4GEM - SBML models for maize, sorghum and sugarcane

de Oliveira Dal'molin CG, Quek LE, Palfreyman RW, Brumbley SM, Nielsen LK (2010) C4GEM - Genome-Scale Metabolic Model to study C4 plant metabolism. Plant Physiol. 154:1871-85. PMID: 20974891.

C4 Flux Toolbox - Matlab Flux Toolbox with maize example

de Oliveira Dal'molin CG, Quek LE, Palfreyman RW, Brumbley SM, Nielsen LK (2010) C4GEM - Genome-Scale Metabolic Model to study C4 plant metabolism. Plant Physiol. 154:1871-85. PMID: 20974891.

iCA1273 version 1.01 - E. coli W genome scale model

Archer CT, Kim JF, Jeong H, Park JH, Vickers CE, Lee SY, Nielsen LK (2011) The genome sequence of E. coli W (ATCC 9637): comparative genome analysis and an improved genome-scale reconstruction of E. coli. BMC Genomics 12:9. PMID: 21208457.

AlgaGEM - AlgaGEM SBML file for use with COBRA Toolbox in Matlab

Dal’Molin CGO, Quek LE, Palfreyman RW, Nielsen LK (2011) AlgaGEM - A genome-scale metabolic reconstruction of Algae based on Chlamydomonas reinhardtii genome. BMC Genomics 12(Supp 4): S5.http://www.biomedcentral.com/1471-2164/12/S4/S5.

Software

We make our software packages available.

Examples of Dirichlet Kernels (Bioinformatics submission)

The attached examples are for a submission in Bioinformatics only. Download: Dirichlet Kernel.zip

Fast-SNP

Saa PA, Nielsen LK (2016) Fast-SNP: a fast matrix pre-processing algorithm for efficient loopless flux optimization of metabolic models. Bioinformatics 32: 3807–3814.

Download: Fast_SNP_v10_10_16.zip

ll-ACHRB

Saa PA, Nielsen LK (2016) ll-ACHRB: a scalable algorithm for sampling the feasible solution space of metabolic networks. Bioinformatics 32: 2330–2337.

ll-ACHRB software ver 1.1 (introduces faster warm up using efficient loopless optimization): ll_ACHRB ver 1.1.zip

B-DMFA

Martínez VS, Buchsteiner M, Gray P, Nielsen LK, Quek LE (2015) Dynamic Metabolic Flux Analysis using B-splines to study the effects of temperature shift on CHO cell metabolism. Met Eng Comm 2: 46-57.

B-DMFA is available either as quadratic spline or generic order.

MultiGEM - multi-tissue GEM framework

Dal'molin CGDO, Quek LE, Saa PA, Nielsen LK (2015) A multi-tissue genome-scale metabolic modelling framework for the analysis of whole plant systems. Front. Plant Sci. 6:4. Online.

Download software from this site.

Supplementary Data for OpenFlux

Quek L-E, Wittmann C, Nielsen LK, Kroemer JO (2009) OpenFLUX: Efficient Modelling Software for 13C-Based Metabolic Flux Analysis. Microbial Cell Factories 8:25. PMID: 19409084.

Quek LE, Nielsen LK (2014) Steady-State 13C Fluxomics Using OpenFLUX. In: Krömer JO, Nielsen LK, Blank LM (eds) Metabolic Flux Analysis: Methods and Protocols. Series: Methods in Molecular Biology, vol. 1191. Chapter 13: 65-78. PMID: 25178793.

Registration (please register for use of OpenFlux)

C. glutamicum model (Excel file)

TCA model (Excel file)

Atom transitions (Excel file)

PathLogic

Fearnley LG, Nielsen LK (2012) PATHLOGIC-S: A scalable Boolean framework for modelling cellular signalling. PLoS ONE 7(8): e41977. PMID: 22879903.

Available from Sourceforge.

Martínez VS, Quek LE, Nielsen LK ( 2014) Network thermodynamic curation of human and yeast genome-scale metabolic models. Biophys J 107:493-503. PMID: 25028891.

Martinez VS, Nielsen LK (2014) NExT: Integration of Thermodynamic Constraints and Metabolomics Data into a Metabolic Network. In: Krömer JO, Nielsen LK, Blank LM (eds) Metabolic Flux Analysis: Methods and Protocols. Series: Methods in Molecular Biology, vol. 1191. Chapter 4: 209-224. PMID: 25178784.

Download software from this site.

COBRA 2014 posters

Pedro Saa: Generalized framework for thermodynamic-consistent parameterization and efficient sampling of enzymatic reactions

Veronica Martinez: Topological flexibility in the Human Genome Scale model Recon 1

2016

Williams TC, Peng B, Vickers CE, Nielsen LK (2016) The Saccharomyces cerevisiae pheromone-response is a metabolically active stationary phase for bio-production. Met Eng Comm, accepted 11.05.2016.

Saa PA, Nielsen LK (2016) ll-ACHRB: a scalable algorithm for sampling the feasible solution space of metabolic networks. Bioinformatics. Accepted 3.3.16. Advance Access 11.03.16. PMID: 27153696

Saa PA, Nielsen LK (2016) Construction of feasible and accurate kinetic models of metabolism: A Bayesian approach. Sci Rep 6:29635. PMID: 27417285

Ormerod KL, Wood DLA, Lachner N, Gellatly SL, Daly JN, Parsons J, Dal'Molin CGO, Palfreyman RW, Nielsen LK, Cooper MA, Morrison M; Hansbro PM, Hugenholtz P (2016) Genomic characterization of the uncultured Bacteroidales family S24-7 inhabiting the guts of homeothermic animals. Microbiome 4: 36. PMID: 27388460

Swainston N, Smallbone K, Hefzi H, Dobson PD, Brewer J, Hanscho M, Zielinski DC, Ang KS, Gardiner NJ, Gutierrez JM, Kyriakopoulos S, Lakshmanan M, Li S, Liu JK, Martínez VS, Orellana CA, Quek LE, Thomas A, Zanghellini J, Borth N, Lee DY, Nielsen LK, Kell DB, Lewis NE, Mendes P (2016) Recon 2.2: from reconstruction to model of human metabolism. Metabolomics 12:109. PMID: 27358602

Luna-Flores C, Nielsen LK, Marcellin E (2016) Genome Sequence of Propionibacterium acidipropionici ATCC 55737. Genome Announcements 4: e00248-16.PMID: 27198010

Marcellin E, Behrendorff JB, Nagaraju S, DeTissera S, Segovia S, Palfreyman RW, Daniell J, Licona-Cassani C, Quek LE, Speight R, Hodson MP, Simpson SD, Mitchell WP, Köpke M, Nielsen LK (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.

Zhang Y, Luo K, Zhao Q, Qi Z, Nielsen LK, Liu H (2015) Genetic and biochemical characterization of genes involved in hyaluronic acid synthesis in Streptococcus zooepidemicus. Appl Microbiol Biotechnol. 100: 3611-20. PMID: 26758299

McQualter RB, Bellasio C, Gebbie LK, Petrasovits LA, Palfreyman RW, Hodson MP, Plan MR, Blackman DM, Brumbley SM, Nielsen LK (2015) Systems biology and metabolic modelling unveils limitations to polyhydroxybutyrate accumulation in sugarcane leaves; lessons for C4 engineering. Plant Biotechnology Journal 14: 567-80. PMID: 26015295

Zhu Y, Pham TH, Nhiep THN, Vu NMT, Marcellin E, Chakrabortti A, Wang Y, Waanders J, Lo R, Huston WM, Bansal N, Nielsen LK, Liang ZX, Turner MS (2015) Cyclic-di-AMP synthesis by the diadenylate cyclase CdaA is modulated by the peptidoglycan biosynthesis enzyme GlmM in Lactococcus lactis. Molecular Microbiology99:1015-21. PMID: 26585449

Dal’Molin CGO, Nielsen LK (2016) Algae Genome-Scale Reconstruction, Modelling and Applications. In: M.A. Borowitzka et al. (eds.) The Physiology of Microalgae. Series: Developments in Applied Phycology, vol. 6, pg. 591-598.

Saa PA, Nielsen LK (2016) A probabilistic framework for the exploration of enzymatic capabilities based on feasible kinetics and control analysis. BBA - General Subjects 1860: 576-587.PMID: 26721334

Schwaber JL, Brunck ME, Levesque JP, Nielsen LK (2016) Filling the void: allogeneic myeloid cells for transplantation. Current Opinion in Hematology 23: 72-7. PMID: 26554894

2015

Licona-Cassani C, Morales PC, Manteca A, Barona-Gomez F, Nielsen LK, Marcellin E (2015) Systems biology approaches to understand natural products biosynthesis. Front. Bioeng. Biotechnol. 3:199. PMID: 26697425

Song MC, Hou JJ, Nielsen LK, Gray PP (2015) Novel cell engineering of the Unfolded Protein Response to achieve efficient therapeutic protein production cell line. BMC Proceedings 9 (S9):P14. doi:10.1186/1753-6561-9-S9-P14.

Orellana CA, Marcellin E, Munro T, Gray PP, Nielsen LK (2015) Multi-omics approach for comparative studies of monoclonal antibody producing CHO cells. BMC Proceedings 9 (S9):O8. doi:10.1186/1753-6561-9-S9-O8.

Bongers M, Chrysanthopoulos PK, Behrendorff JBYH, Hodson MP, Vickers CE, Nielsen LK (2015) Systems analysis of methylerythritol-phosphate pathway flux in E. coli: insights into the role of oxidative stress and the validity of lycopene as an isoprenoid reporter metabolite. Microbial Cell Factories 14: 193. PMID: 26610700

Medina-Torres CE, van Eps AW, Nielsen LK, Hodson MP (2015) A liquid chromatography–tandem mass spectrometry-based investigation of the lamellar interstitial metabolome in healthy horses and during experimental laminitis induction. The Veterinary Journal 206: 161-9. PMID: 26364239

Ebrahim A, Almaas E, Bauer E, Bordbar A, Burgard AP, Chang RL, Dräger A, Famili I, Feist AM, Fleming RM, Fong SS, Hatzimanikatis V, Herrgård MJ, Holder A, Hucka M, Hyduke D, Jamshidi N, Lee SY, Le Novère N, Lerman JA, Lewis NE, Ma D, Mahadevan R, Maranas C, Nagarajan H, Navid A, Nielsen J, Nielsen LK, Nogales J, Noronha A, Pal C, Palsson BO, Papin JA, Patil KR, Price ND, Reed JL, Saunders M, Senger RS, Sonnenschein N, Sun Y, Thiele I (2015) Do genome-scale models need exact solvers or clearer standards? Mol Syst Biol 11:831. PMID: 26467284

Navone L, Macagno JP, Licona-Cassani C, Marcellin E, Nielsen LK, Gramajo H, Rodriguez E (2015) AllR controls the expression of Streptomyces coelicolor allantoin pathway genes. Appl Env Microbiol 81: 6649-59. PMID: 26187964

Huynh HT, Tran TT, Chan LC, Nielsen LK, Reid S (2015) Decline in Helicoverpa armigera nucleopolyhedrovirus occlusion body yields with increasing infection cell density in vitro is strongly correlated with viral DNA levels. Arch Virol 160: 2169-80. PMID: 26092423

McQualter RB, Petrasovits LA, Gebbie LK, Schweitzer D, Blackman DM, Plan MR, Hodson MP, Riches JD, Snell KD, Brumbley SM, Nielsen LK (2015) The use of an acetoacetyl-CoA synthase in place of a β-ketothiolase enhances poly-3-hydroxybutyrate production in sugarcane mesophyll cells. Plant Biotechnology Journal 13: 700-7. PMID: 25532451

Peng BY, Williams TC, Henry M, Nielsen LK, Vickers CE (2015) Controlling heterologous gene expression in yeast cell factories on different carbon substrates and across the diauxic shift: a comparison of yeast promoter activities. Microbial Cell Factories 14:91.PMID: 26112740

Lim S, Marcellin E, Jacob S, Nielsen LK (2015) Global dynamics of Escherichia coli phosphoproteome in central carbon metabolism under changing culture conditions. J Proteomics 126: 24-33. PMID: 26013414

Matindoost L, Nielsen LK, Reid S (2015) Intracellular trafficking of baculovirus virions - a quantitative study of the HearNPV/HzAM1 cell and AcMNPV/Sf9 cell systems. Viruses 7: 2288-2307. PMID: 25951488

Brennan TCR, Williams TC, Schulz BL, Palfreyman RW, Krömer JO, Nielsen LK (2015) Evolutionary engineering improves tolerance for replacement jet fuels in Saccharomyces cerevisiae. Appl Environ Microbiol 81: 3316 –3325. PMID: 25746998

Saa PA, Nielsen LK (2015) A general framework for thermodynamically consistent parameterization and efficient sampling of enzymatic reactions. PLoS Comp Bio 11:e1004195. PMID: 25874556

Williams TC, Averesch NJH, Winter G, Plan MR, Vicker CE, Nielsen LK, Krömer JO (2015) Quorum-sensing linked RNA interference for dynamic metabolic pathway control in Saccharomyces cerevisiae. Metabolic Engineering 29: 124-134. PMID: 25792511

Williams TC, Gomez ME, Nielsen LK, Vickers CE (2015) Dynamic regulation of gene expression using sucrose responsive promoters and RNA interference in Saccharomyces cerevisiae. Microbial Cell Factories14:43. PMID: 25886317

Clark MB, Mercer TR, Bussotti G, Leonardi T, Haynes KR, Crawford J, Brunck ME, Cao KAL, Thomas GP, Chen WY, Taft RJ, Nielsen LK, Enright AJ, Mattick JS, Dinger ME (2015) Quantitative gene profiling of long noncoding RNAs with targeted RNA sequencing. Nature Methods 12: 339-342. PMID: 25751143

Orellana CA, Marcellin E, Schulz BL, Nouwens AS, Gray PP, Nielsen LK (2015) High antibody producing Chinese hamster ovary cells up-regulate intracellular protein transport and glutathione synthesis. J Proteome Res 14: 609–618. PMID: 25495469

Huynh HT, Tran TT, Chan LC, Nielsen LK, Reid S (2015) Effect of the peak cell density of recombinant AcMNPV-infected Hi5 cells on baculovirus yields. Appl Microbiol Biotechnol 99:1687-1700. PMID: 25472440

Mercer TR, Clark MB, Andersen SB, Brunck ME, Haerty W, Crawford J, Taft RJ, Nielsen LK, Dinger ME, Mattick JS (2015) Genome-wide discovery of human splicing branchpoints. Genome Res 25: 290-303. PMID: 25561518

Dal'Molin CGDO, Quek LE, Saa PA, Nielsen LK (2015) A multi-tissue genome-scale metabolic modelling framework for the analysis of whole plant systems. Front. Plant Sci. 6:4. PMID: 25657653

Vickers CE, Behrendorff JBYH, Bongers M, Brennan TCR, Bruschi M, Nielsen LK (2015) Production of industrially relevant isoprenoid compounds in engineered microbes. In: Kamm B (ed) Microorganisms in Biorefineries. Series: Microbiology Monographs, vol. 26. Chapter 11: 303-334.

2014

Jardine K, Chambers J, Alves EG, Teixeira A, Garcia S, Holm J, Higuchi N, Manzi A, Abrell L, Fuentes JD, Nielsen LK, Torn M, Vickers CE (2014) Dynamic balancing of isoprene carbon sources reflects photosynthetic and photorespiratory responses to temperature stress. Plant Physiology 166: 2051-64. PMID: 25318937.

Turner J, Quek LE, Titmarsh D, Krömer JO, Kao LP, Nielsen LK, Wolvetang E, Cooper-White J (2014) Metabolic profiling and flux analysis of MEL-2 human embryonic stem cells during exponential growth at physiological and atmospheric oxygen concentrations. PLoS ONE 9: e112757. PMID: 25412279. Online.

McQualter RB, Somleva MN, Gebbie LK, Li X, Petrasovits LA, Snell KD, Nielsen LK, Brumbley SM (2014) Factors affecting polyhydroxybutyrate accumulation in mesophyll cells of sugarcane and switchgrass. BMC Biotechnology 14: 83.PMID: 25209261. Online.

Fearnley LG, Davis MJ, Ragan MA, Nielsen LK (2014) Extracting Reaction Networks from Databases – Opening Pandora’s Box. Briefings in Bioinformatics 15: 973-983. PMID: 23946492. Online

Quek LE, Nielsen LK (2014) Steady-State 13C Fluxomics Using OpenFLUX. In: Krömer JO, Nielsen LK, Blank LM (eds) Metabolic Flux Analysis: Methods and Protocols. Series: Methods in Molecular Biology, vol. 1191. Chapter 13: 65-78. PMID: 25178793.

Quek LE, Nielsen LK (2014) Customization of 13C-MFA Strategy According to Cell Culture System. In: Krömer JO, Nielsen LK, Blank LM (eds) Metabolic Flux Analysis: Methods and Protocols. Series: Methods in Molecular Biology, vol. 1191. Chapter 5: 81-90. PMID: 25178785.

Martinez VS, Nielsen LK (2014) NExT: Integration of Thermodynamic Constraints and Metabolomics Data into a Metabolic Network. In: Krömer JO, Nielsen LK, Blank LM (eds) Metabolic Flux Analysis: Methods and Protocols. Series: Methods in Molecular Biology, vol. 1191. Chapter 4: 209-224. PMID: 25178784.

Bruschi M, Krömer JO, Steen JA, Nielsen LK (2014) Production of the short peptide surfactant DAMP4 from glucose or sucrose in high cell density cultures of Escherichia coli BL21(DE3). Microbial Cell Factories13:99. PMID: 25134850. Online.

Arifin Y, Archer C, Lim SA, Quek L-E, Sugiarto H, Marcellin E, Vickers CE, Krömer JO, Nielsen LK (2014) Escherichia coli W shows fast, highly oxidative sucrose metabolism and low acetate formation. Applied Microbiology and Biotechnology 98: 9033-44. PMID: 25125039.

Quek LE, Nielsen LK (2014) A depth-first search algorithm to compute elementary flux modes by linear programming. BMC Systems Biology 8:94. PMID: 25074068. Online.

Martínez VS, Quek LE, Nielsen LK ( 2014) Network thermodynamic curation of human and yeast genome-scale metabolic models. Biophys J 107:493-503. PMID: 25028891.

Liao C, Rigali S, Cassani CL, Marcellin E, Nielsen LK, Ye BC (2014) Control of Chitin and N-acetylglucosamine Utilization in Saccharopolyspora erythraea. Microbiology 160: 1914–1928. PMID: 25009237.

Brunck MEG, Andersen SB, Timmins NE, Osborne GW, Nielsen LK (2014) Absolute counting of neutrophils in whole blood using flow cytometry. Cytometry 85: 1057-64. PMID: 24995861.

Marcellin E, Steen JA, Nielsen LK (2014) Insight into hyaluronic acid molecular weight control. Applied Microbiology and Biotechnology 98: 6947-56. PMID: 24957250.

Quek LE, Dietmair S, Hanscho M, Martinez VS, Borth N, Nielsen LK (2014) Reducing Recon 2 for steady-state flux analysis of HEK cell culture. J Biotech 184: 172-178. PMID: 24907410.

Licona-Cassani C, Lim SA, Marcellin E, Nielsen LK (2014) Temporal dynamics of the Saccharopolyspora erythraea phosphoproteome. Molecular and Cellular Proteomics 13: 1219-1230. PMID: 24615062

Brunck MEG, Nielsen LK (2014) Next generation cell therapies to prevent infections in neutropenic patients. Stem cells translational medicine 3: 541-548. PMID: 24598780

Mercer TR, Clark MB, Crawford J, Brunck ME, Gerhardt D, Taft R, Nielsen LK, Dinger M, Mattick JS (2014) Targeted sequencing for gene discovery and quantification using RNA CaptureSeq. Nat Protoc 9: 989-1009. PMID: 24705597

Fearnley LG, Ragan MA, Nielsen LK (2014) Towards a Large Integrated Model of Signal Transduction and Gene Regulation Events in Mammalian Cells. In: Proceedings of the International Conference on Bioinformatics Models, Methods and Algorithms, pg 117-122.

Chen WY, Marcellin E, Steen JA, Nielsen LK (2014) The role of hyaluronic acid precursor concentrations in molecular weight control in Streptococcus zooepidemicus. Mol Biotechnol 56:147–156.PMID: 23903961

Steen JA, Bohlke N, Vickers CE, Nielsen LK(2014) The trehalose phosphotransferase system (PTS) in E. coli W can transport low levels of sucrose that are sufficient to facilitate induction of the csc sucrose catabolism operon. PLoS ONE 9:e88688.PMID: 24586369. Online

Navone L, Casati P, Licona-Cassani C, Marcellin E, Nielsen LK, Rodriguez E, Gramajo H (2014) Allantoin catabolism influences the production of antibiotics in Streptomyces coelicolor. Appl Microbiol Biotechnol98:351-360. PMID: 24292080

Matindoost L, Hu H, Chan LC, Nielsen LK, Reid S (2014) The effect of cell line, phylogenetics and medium on baculovirus budded virus yield and quality. Arch Virol. 159: 91-102. PMID: 23884632

Dal’Molin CGO, Quek L-E, Palfreyman RW, Nielsen LK (2014) Plant Genome-Scale Modeling and Implementation. In: Dieuaide-Noubhani M, Alonso AP, editors. Plant Metabolic Flux Analysis: Methods & Protocols. Humana Press. Methods in Molecular Biology 1090: 317-32. PMID: 24222424

2013

Peatey CL, Watson JA, Trenholme KR, Brown CL, Nielsen LK, Guenther M, Timmins NE, Watson GS, Gardiner DL (2013) Enhanced gametocyte formation in erythrocyte progenitor cells: a site specific adaptation by Plasmodium falciparum. J Infect Dis 208: 1170-1174. PMID: 23847056

Petrasovits LA, McQualter RB, Gebbie L, Blackman D, Nielsen LK, Brumbley SM (2013) Chemical inhibition of Acetyl Coenzyme A Carboxylase as a strategy to increase polyhydroxybutyrate yields in transgenic sugarcane. Plant Biotechnol J 11: 1146-1151. PMID: 24112832

Nguyen Q, Nielsen LK, Reid S (2013) Genome Scale Transcriptomics of Baculovirus-Insect Interactions. Viruses 5: 2721-2747. PMID: 24226166. PMC3856412

Vickers CE, Bydder SF, Zhou Y, Nielsen LK (2013) Dual gene expression cassette vectors with antibiotic selection markers for engineering in Saccharomyces cerevisiae. Microbial Cell Factories 12: 96. PMID: 24161108. Open access.

Marcellin E, Licona-Cassani C, Mercer TR, Palfreyman RW, Nielsen LK (2013) Re-annotation of the Saccharopolyspora erythraea genome using a systems biology approach. BMC Genomics 14:699. PMID: 24118942. Open access

Nguyen QH, Chan LCL, Nielsen LK, Reid S (2013) Genome scale analysis of differential mRNA expression of Helicoverpa zea insect cells infected with a H. armigera baculovirus. Virology 444: 158-170. PMID:23827436

Klein-Marcuschamer D, Turner C, Allen M, Dietzgen RG, Gray P, Gresshoff P, Hankamer B, Heimann K, Scott P, Speight R, Stephens E, Nielsen LK (2013) Analysis of renewable aviation fuel from microalgae, Pongamia pinnata, and sugarcane. Biofuels, Bioproducts & Biorefining 7:416-428.

Behrendorff JBYH, Vickers CE, Chrysanthopoulos P, Nielsen LK (2013) 2,2-Diphenyl-1-picrylhydrazyl as a screening tool for recombinant monoterpene biosynthesis. Microbial Cell Factories 12:76. PMID: 23968454. PMC3847554

Mercer TR, Edwards SL, Clark MB, Neph SJ, Wang H, Stergachis AB, John S, Sandstrom R, Li G, Sandhu KS, Ruan Y, Nielsen LK, Mattick JS, Stamatoyannopoulos JA (2013) DNase I-hypersensitive exons co-localize with promoters and distal regulatory elements. Nature Genetics 45:852-9. PMID: 23793028

Sabri S, Steen JA, Bongers M, Nielsen LK, Vickers CE (2013) Knock-in/Knock-out (KIKO) vectors for rapid integration of large DNA sequences, including whole metabolic pathways, onto the Escherichia colichromosome at well-characterised loci. Microbial Cell Factories 12:60. PMID: 23799955. PMC3706339

Brennan TCR, Kr?mer JO, Nielsen LK (2013) Physiological and transcriptional response to d-limonene in Saccharomyces cerevisiae shows changes to the cell wall, not the plasma membrane. Appl Env Microbiol79: 3590-3600. PMID: 23542628

O’Neill BP, Purnell MP, Kurniawan ND, Cowin GJ, Galloway GJ, Nielsen LK, Brumbley SM (2013) Non-Invasive Monitoring of Sucrose Mobilization from Culm Storage Parenchyma by Magnetic Resonance Spectroscopy. Bioscience, Biotechnology, and Biochemistry 77: 487-496. PMID: 23470752

Huynh HT, Tran TTB, Chan LCL, Nielsen LK, Reid S (2013) Decline in baculovirus-expressed recombinant protein production with increasing cell density is strongly correlated to impairment of virus replication and mRNA expression. Appl Microbiol Biotechnol 97:5245–5257. PMID: 23519736

Williams TC, Nielsen LK, Vickers CE (2013) Engineered quorum-sensing using pheromone-mediated cell-to-cell communication in Saccharomyces cerevisiae. ACS Synthetic Biology 2: 136-149. PMID: 23656437

Marcellin E, Mercer TR, Licona-Cassani C, Palfreyman RW, Dinger M, Steen JA, Mattick JS, Nielsen LK (2013) Saccharopolyspora erythraea's genome is organised in high-order transcriptional regions mediated by targeted degradation at the metabolic switch. BMC Genomics 14:15. PMID: 23324121. PMC3610266

Mart?nez VS, Dietmair S, Quek L-E, Hodson MP, Gray P, Nielsen LK (2012) Flux balance analysis of CHO cells before and after a metabolic switch from lactate production to consumption. Biotechnology & Bioengineering 110: 660-666. PMID: 22991240

Sabri S, Nielsen LK, Vickers CE (2013) Molecular control of sucrose utilization in Escherichia coli W, an efficient sucrose-utilizing strain. Appl Env Microbiol 79: 478-487. PMID: 23124236. PMC3553775

Dal’Molin CGO, Nielsen LK (2013) Plant genome-scale metabolic reconstruction and modelling. Curr Opin Biotechnol. 24: 271-277. PMID: 22947602

2012

O’Neill BP, Purnell MP, Nielsen LK, Brumbley SM (2012) RNAi-mediated abrogation of trehalase expression does not affect trehalase activity in sugarcane. SpringerPlus 1:74. PMID: 23539210. PMC3606522

Dietmair S, Hodson MP, Quek L-E, Timmins NE, Gray P, Nielsen LK (2012) A multi-omics analysis of recombinant protein production in Hek293 cells. PLoS ONE 7(8):e43394. PMID: 22937046. PMC3427347

Licona-Cassani C, Marcellin E, Quek L-E, Jacob S, Nielsen LK (2012) Reconstruction of the Saccharopolyspora erythraea genome-scale model and its use for enhancing erythromycin production. Antonie van Leeuwenhoek 102: 493-502. PMID: 22847261

Utrilla J, Licona-Cassani C, Marcellin E, Gosset G, Nielsen LK, Martinez A (2012) Engineering and adaptive evolution of Escherichia coli for D-lactate fermentation reveals GatC as a xylose transporter. Metabolic Engineering 14: 469–476. PMID: 22885034

Fearnley LG, Nielsen LK (2012) PATHLOGIC-S: A scalable Boolean framework for modelling cellular signalling. PLoS ONE 7(8): e41977. PMID: 22879903. PMC3413702

Brennan TCR, Turner CD, Kr?mer JO, Nielsen LK (2012) Alleviating monoterpene toxicity using a two-phase extractive fermentation for the bioproduction of jet fuel mixtures in Saccharomyces cerevisiae.Biotechnology & Bioengineering 109: 2513-2522. PMID: 22539043

Doran M, Aird I, Marturana F, Timmins NE, Atkinson K, Nielsen LK (2012) Bioreactor for Blood Production. Cell Transplantation 21: 1235-1244. PMID: 22405378

Bruschi M, Boyes SJ, Sugiarto H, Nielsen LK, Vickers CE (2012) A transferable sucrose utilization approach for non-sucrose-utilizing Escherichia coli strains. Biotechnology Advances 30: 1001-1010. PMID:21907272.

Matindoost L, Chan LCL, Qi YM, Nielsen LK, Reid S (2012) Suspension culture titration: A simple method for measuring baculovirus titers. Journal of Virological Methods 183: 201–209. PMID: 22561639

Huynh HT, Chan LCL, Tran TTB, Nielsen LK, Reid S (2012) Improving the robustness of a low-cost insect cell medium for baculovirus biopesticides production, via hydrolysate streamlining using a tube bioreactor-based statistical optimization routine. Biotechnology Prog 28: 788-802. PMID: 22323401

Vickers CE, Klein-Marcuschamer D, Kr?mer JO (2011) Examining the feasibility of bulk commodityproduction in Escherichia coli. Biotechnology Letters 34: 585-96. PMID: 22160295.

O’Neill BP, Purnell MP, Anderson DJ, Nielsen LK, Brumbley SM (2012) Sucrose mobilisation in sugarcane stalk induced by heterotrophic axillary bud growth. Tropical Plant Biology 5:173-182.

Dietmair S, Nielsen LK, Timmins NE (2011) Mammalian cells as biopharmaceutical production hosts in the age of omics. Biotechnol J 7: 75-89. PMID: 22180043

Nguyen QH, Palfreyman RW, Chan LCL, Reid S, Nielsen LK (2012) Transcriptome sequencing of and microarray development for a Helicoverpa zea cell line to investigate in vitro insect cell-baculovirus interactions. PloS ONE 7(5):e36324. PMID: 22629315. PMC3356360

Dietmair S, Hodson MP, Quek LE, Timmins NE, Chrysanthopoulos P, Jacob SS, Gray P, Nielsen LK (2012)Metabolite profiling of CHO cells with different growth characteristics. Biotechnol. Bioeng. 109: 1404-1414. PMID: 22407794

Tran TTB, Dietmair S, Chan LCL, Huynh HT, Nielsen LK, Reid S (2012) Development of quenching and washing protocols for quantitative intracellular metabolite analysis of uninfected and baculovirus-infected insect cells. Methods 56: 396-407. PMID: 22166686

Petrasovits LA, Zhao L, McQualter RB, Snell KD, Somleva MN, Patterson NA, Nielsen LK, Brumbley SM (2012) Enhanced polyhydroxybutryate production in transgenic sugarcane. Plant Biotechnol J 10: 569-578..PMID: 22369516

Dietmair S, Timmins NE, Chrysanthopoulos P, Gray PP, Kr?mer JO, Nielsen LK (2012) Metabolomic analysis of CHO cultures with different growth characteristics - Development of a metabolite extraction protocol for suspension adapted mammalian cells In N. Jenkins, N Barron, PM Alves (Ed.) Proceedings of the 21st Annual Meeting of the European Society for Animal Cell Technology (ESACT), Dublin, Ireland, June 7-10, 2009 (pp. 37-41) Dordrecht, Netherlands: Springer.

Timmins NE, Nielsen LK (2012) Large scale manufacture of blood cells. In N. Jenkins, N Barron, PM Alves (Ed.) Proceedings of the 21st Annual Meeting of the European Society for Animal Cell Technology (ESACT), Dublin, Ireland, June 7-10, 2009 (pp. 557-571) Dordrecht, Netherlands: Springer.

2011

Anderson DJ, Gnanasambandam A, Williams E, O’Shea MG, Nielsen LK, Brumbley SM (2011) Synthesis of short-chain-length/medium-chain length polyhydroxyalkanoate (PHA) copolymers in peroxisomes of transgenic sugarcane plants. Tropical Plant Biology 4: 170-184.

Arafin Y, Sabri S, Sugiarto H, Kromer JO, Vickers CE, Nielsen LK (2011) Deletion of cscR in Escherichia coli W improves growth and poly-3-hydroxyburyrate (PHB) production from sucrose in fed batch culture. J. Biotechnol. 156: 275-278. PMID: 21782859.

Timmins NE, Athanasas S, G?nther M, Buntine P, Nielsen LK (2011) Ultra high yield manufacture of red blood cells from hematopoietic stem cells. Tissue Engineering, Part C 17: 1131-7. PMID: 21736478.

Timmins NE, Nielsen LK (2011) Manufactured RBC - rivers of blood, or an oasis in the desert? Biotechnology Advances 29: 661-6. PMID: 21609758.

Wicks JR, Oldridge NB, Nielsen LK, Vickers CE (2011) Heart Rate Index - A Simple Method for Prediction of Oxygen Uptake. Med Sci Sports Exerc. 43: 2005-2012. PMID: 21364476.

Marcellin E, Chen WY, Nielsen LK (2011) Metabolic Pathway Engineering for Hyaluronic Acid Production. In: Carbohydrate Modifying Biocatalysts, ed. P. Grundwald. Pan Stanford Publishing. ISBN: 978-9814241670. Published 30.9.2011. Chapter 15, pp. 571-584.

Etebari K, Palfreyman RW, Schlipalius D, Nielsen LK, Glatz RV, Asgari S (2011) Deep sequencing-based transcriptome analysis of Plutella xylostella larvae parasitized by Diadegma semiclausum. BMC Genomics12:446. PMID: 21906285.

Nielsen LK (2011) METABOLIC ENGINEERING From retrofitting to green field. Nature Chemical Biology 7: 407-408. PMID: 21685882.

Dietmair S, Nielsen LK, Timmins NE (2010) Engineering a mammalian super producer. Journal of Chemical Technology & Biotechnology 86: 905–914.

Kr?mer JO, Dietmair S, Jacob SS, Nielsen LK (2011) Quantification of L-alanyl-L-glutamine in mammalian cell culture broth - evaluation of different detectors. Analytical Biochemistry 416:129-31. PMID:21651886.

Nguyen Q, Qi YM, Wu Y, Chan LCL, Nielsen LK, Reid S (2011) In vitro production of Helicoverpa baculovirus biopesticides - Automated selection of insect cell clones for manufacturing and systems biology studies. J. Virol. Meth. 175: 197-205. PMID: 21616093.

Pedrini MRS, Reid S, Nielsen LK, Chan LCL (2010) Kinetic characterization of the Group II Helicoverpa armigera nucleopolyhedrovirus propagated in suspension cell cultures: implications for development of a biopesticides production process. Biotechnology Progress 27: 614-24. PMID: 21644255.

Rabaey K, Girguis P, Nielsen LK (2011) Metabolic and practical considerations on microbial electrosynthesis. Curr Opin Biotechnol. 22: 371-7. PMID: 21353525.

Li J, Wijffels G, Yu Y, Nielsen LK, Niemeyer DO, Fisher AD, Ferguson DM, Schirra HJ (2011) Altered Fatty Acid Metabolism in Long Duration Road Transport: An NMR-based Metabonomics Study in Sheep. J Proteome Res. 10: 1073-87. PMID: 21142080.

Marturana F, Timmins NE, Nielsen LK (2011) Short term exposure of umbilical cord blood CD34+ cells to GM-CSF early in culture improves ex vivo expansion of neutrophils. Cytotherapy 13: 366-77. PMID:20860426.

2010

de Oliveira Dal'molin CG, Quek LE, Palfreyman RW, Brumbley SM, Nielsen LK (2010) C4GEM - Genome-Scale Metabolic Model to study C4 plant metabolism. Plant Physiol. 154:1871-85. PMID: 20974891.

Vickers CE, Blank LM, Kroemer JO (2010) Chassis cells for industrial biochemical production. Nature Chemical Biology 6: 875-877. PMID: 21079595.

Osiecki M, Ghanavi P, Atkinson K, Nielsen LK, Doran M (2010) The Ascorbic Acid Paradox. Biochemical and Biophysical Research Communications 400: 466-470. PMID: 20732307

Lee JW, Choi S, Park JH, Vickers CE, Nielsen LK, Lee SY (2010) Development of sucrose-utilizing Escherichia coli K-12 strain by cloning β-fructofuranosidases and its application for L-threonine production. Appl Microbiol Biotechnol 88: 905-13. PMID: 20711572.

Chen LCL, Reid S, Nielsen LK (2010) Baculovirus virus kinetics in insect cell culture. In: Encyclopedia of Industrial Biotechnology: Bioprocess, Bioseparation, and Cell Technology, ed. MC Flickinger. John Wiley & Sons. ISBN: 978-0-471-79930-6. Publication date: March 2010.

Dietmair S, Timmins NE, Gray PP, Nielsen LK, Kr?mer JO (2010) Toward quantitative metabolomics of mammalian cells: Development of a metabolite extraction protocol. Analytical Biochemistry 404:155-164. PMID: 20435011.

Doran MR, Markway B, Clark A, Athanasas-Platsis S, Brooke G, Atkinson K, Nielsen LK, Cooper-White JJ (2010) Membrane Bioreactors Enhance Microenvironmental Conditioning and Tissue Development. Tissue Engineering Part C: Methods. 16:407-415. PMID: 19622005.

Leung A, Nielsen LK, Trau M, Timmins NE (2010) Tissue Transplantation by Stealth - Coherent Alginate Microcapsules for Immunoisolation. Biochem Eng J 48:337-347. doi:10.1016/j.bej.2009.10.007.

Quek L-E, Dietmair S; Kr?mer JO, Nielsen LK (2010) Metabolic flux analysis in mammalian cell culture. Metabolic Engineering 12: 161-171. PMID: 19833223.

Marcellin E, Chen W, Nielsen LK (2010) Understanding plasmid effect on hyaluronic acid molecular weight produced by Streptococcus equi subsp. zooepidemicus. Metabolic Engineering 12: 62–69. PMID: 19782148.

Joachimsthal EL, Reeves RKH, Hung J, Nielsen LK, Ouwerkerk D, Klieve AV, Vickers CE (2010) Production of bacteriocins by Streptococcus bovis strains from Australian ruminants. Journal of Applied Microbiology108: 428-436. PMID: 19614851.