Dr Birgitta Ebert

FaBA Future Academic Leader in Ferm

Australian Institute for Bioengineering and Nanotechnology
birgitta.ebert@uq.edu.au
+61 7 334 64280

Overview

Birgitta Ebert’s research focuses on developing biotechnology concepts to address critical challenges such as pollution, climate change and overexploitation of natural resources.

She specializes in improving microbial catalysts for eco-friendly chemical and material production by leveraging metabolic engineering, synthetic biology, systems analysis, and modelling. Her goal is to create microbial cell factories that convert renewable resources and waste into valuable products, reducing reliance on petrochemicals. She collaborates closely with chemists and chemical engineers to enhance the integration of chemical and biological processes for improved efficiency and sustainability.

Birgitta has a background in Chemical Engineering and a PhD in Systems Biotechnology from TU Dortmund University (Germany). She led a research group in Systems Metabolic Engineering at the Institute of Applied Microbiology at RWTH Aachen University (Germany) from 2012 to 2019. In 2016, she expanded her expertise in Synthetic Biology by joining the Keasling lab at the University of California in Berkeley and the Joint BioEnergy Institute in Emeryville (USA).

Since April 2019, she has been at the Australian Institute for Bioengineering and Nanotechnology at the University of Queensland, applying her expertise to engineer microbial cell factories for fermentation-based manufacturing.

Research Interests

  • Microbial Biotechnology
  • Synthetic Biology
  • Systems Metabolic Engineering
  • Bioeconomy

Qualifications

  • Doctor of Philosophy, TU Dortmund University

Publications

View all Publications

Supervision

View all Supervision

Available Projects

  • The yeast Saccharomyces cerevisiae is widely used in fermentation to produce wine, beer, and bioethanol. However, this well-researched microbe can also be efficiently engineered for the production of complex natural products. Well-known examples are the anti-malaria drug artemisinin are the ant-cancer drug paclitaxel.

    In this project, we are interested in the production of triterpenoids, the largest group in the natural product class. Many of these molecules have biological activities that make them promising candidates for pharma, nutraceutical, or cosme(ceu)tical applications.

    We have engineered a superior S. cerevisiae platform strain capable of the synthesis of diverse triterpenoids at the gram-scale level. In this project, we aim to expand the product spectrum to alpha-amyrin type triterpenoids with anti-ageing and anti-obesity properties that are used are investigated for use in cosmetics and pharmaceuticals.

    You will recombinantly express plant enzymes in the yeast chassis to enable the production of a few target products. You will further address a major bottleneck in the production of triterpenoids, the intracellular accumulation of the products, which results in cell toxification and low production efficiency. We are following alternative and complementary approaches including the expression of recently identified transporter, in situ extraction and optimization of the intracellular product trafficking route.

    You will gain in-depth knowledge on the metabolism of S. cerevisiae and practical skills in metabolic engineering and synthetic biology including, molecular biology, omics analyses, microscopy, fermentation, and analytics.

    Honours and (under)graduate students are welcomed to work on specific subprojects.

    Please contact me for further information.

  • Modern protein-based vaccines require adjuvants to improve immunogenicity and hence efficacy. The natural product class of triterpenoids includes molecules that have been shown to be very potent vaccine adjuvants. From these candidates, squalene and Quillaja saponins have been approved for their use in vaccines against flu, shingles and malaria. And many more triterpenoid-adjuvanted vaccines are in the pipeline.

    These molecules are currently sourced from animal and plant-derived sources. Squalene is found in high abundance in the liver oil from (deep-sea) sharks and currently the only approved source for medical applications. The Quillaja saponins contained in QS-21 adjuvants are only produced by specific trees in limited regions in South America. Both species, sharks and Quillaja saponaria, are threatened by overexploitation. With the increasing demand for potent vaccines, this is expected to increase.

    In this project, we are working on the biotechnological production of these compounds with engineered Baker's yeast Saccharomyces cerevisiae. We can produce squalene and QS-21 precursors at the gram-scale level, which is the current state of the art.

    Within this larger project, two HDR projects are available focusing on (a) improving squalene production and secretion of the intracellular storage molecule into the fermentation medium, and (b) implementing the complex QS-21 biosynthesis pathways in the yeast chassis.

    Honours and (under)graduate students are welcomed to work on specific subprojects.

    You will gain in-depth knowledge on the metabolism of S. cerevisiae and practical skills in metabolic engineering and synthetic biology including, molecular biology, omics analyses, microbiological work, fermentation, and analytics.

    Please contact me for further information.

  • Redox cofactors play a central role in the metabolism of living organisms. The most widely used cofactor is NAD(P)H. In the central carbon metabolism, the oxidised form NAD(P)+ is the primary acceptor for electrons from carbon oxidation. These electrons are then fed into the electron transfer chain, powering the respiratory system for ATP and thus energy generation. Although efficient, this system leads to CO2 formation via the oxidation of carbon metabolites and, hence, to CO2 emissions during biotechnological processes. In this project, we investigate alternative systems for NADH regeneration with electrons from sustainable energy sources, ultimately decoupling energy and carbon metabolism. Our focus lies hereby on hydrogenases. These enzymes use electrons from hydrogen to generate NADH instead of carbon metabolites, while hydrogen can be produced solely from water and electrons from renewable energy sources. Implementing efficient hydrogenase-based NADH regeneration systems in vivo should lead to more carbon-efficient and sustainable biotechnological processes for a greener bio-based future.

    We’re looking for a motivated student interested in carbon-efficient biological processes. The project offers options for working in molecular biology, bioprocess development, and robotics. Please get in touch with me for further information.

View all Available Projects

Publications

Book Chapter

  • Satta, Alessandro, Lu, Zeyu, Plan, Manuel R., Esquirol, Lygie and Ebert, Birgitta E. (2022). Microbial production, extraction, and quantitative analysis of isoprenoids. Plant Secondary Metabolism Engineering: methods and protocols.. (pp. 239-259) New York, NY, United States: Humana Press. doi: 10.1007/978-1-0716-2185-1_20

  • Halbfeld, Christoph, Baumbach, Jörg Ingo, Blank, Lars M. and Ebert, Birgitta E. (2018). Multi-capillary column ion mobility spectrometry of volatile metabolites for phenotyping of microorganisms. Synthetic metabolic pathways: methods and protocols. (pp. 229-258) New York, NY, United States: Humana Press. doi: 10.1007/978-1-4939-7295-1_15

  • Schmitz, Andreas, Ebert, Birgitta E. and Blank, Lars M. (2015). GC-MS-Based Determination of Mass Isotopomer Distributions for 13C-Based Metabolic Flux Analysis. Hydrocarbon and lipid microbiology protocols: genetic, genomic and system analyses of pure cultures. (pp. 223-243) edited by Terry J. McGenity, Kenneth N. Timmis and Balbina Nogales. Berlin, Heidelberg: Springer Berlin Heidelberg. doi: 10.1007/8623_2015_78

  • Ebert, Birgitta E. and Blank, Lars M. (2014). Successful downsizing for high-throughput 13C-MFA applications. In Jens O. Krömer, Lars K. Nielsen and Lars M. Blank (Ed.), Metabolic flux analysis: methods and protocols (pp. 127-142) New York, NY, United States: Humana Press. doi:10.1007/978-1-4939-1170-7_8

  • Bühler, Bruno, Blank, Lars M., Ebert, Birgitta E., Bühler, Katja and Schmid, Andreas (2009). Energy and cofactor issues in fermentation and oxyfunctionalization processes. The Metabolic Pathway Engineering Handbook: Tools and Applications. (pp. 21-1-21-32) CRC Press.

Journal Article

Conference Publication

  • Lehnen, M., Ebert, B. E. and Blank, L. M. (2016). Development of mini-bioreactors for evolution of thermotolerance. 11th Metabolic Engineering Conference 2016, Awaji Island, Japan, 26 - 30 June, 2016. New York, NY, United States: AIChE.

  • Tokic, M., Hadadi, N., Ataman, M., Miskovic, L., Neves, P., Ebert, B. E., Blank, L. M. and Hatzimanikatis, V. (2016). Discovery and evaluation of novel pathways for production of the second generation of biofuels. 11th Metabolic Engineering Conference 2016, Awaji Island, Japan, 26 - 30 June, 2016. New York, NY, United States: AIChE.

  • Ebert, B. E., Czarnotta, E., Walter, K., Knuf, C., Maury, J., Jacobsen, S. A., Lewandowski, A., Polakowski, T., Lang, C., Forster, J. and Blank, L. M. (2016). Metabolic engineering of saccharomyces cerevisiae for cyclic terpenoid production. 11th Metabolic Engineering Conference 2016, Awaji Island, Japan, 26 - 30 June, 2016. New York, NY, United States: AIChE.

  • Ulonska, Kirsten, Ebert, Birgitta E., Blank, Lars M., Mitsos, Alexander and Viell, Jörn (2015). Systematic screening of fermentation products as future platform chemicals for biofuels. 12th International Symposium on Process Systems Engineering and 25th European Symposium on Computer Aided Process Engineering, Copenhagen, Denmark, 31 May - 4 June 2015. Amsterdam, Netherlands: Elsevier. doi: 10.1016/b978-0-444-63577-8.50067-x

PhD and MPhil Supervision

Current Supervision

  • Doctor Philosophy — Principal Advisor

  • Doctor Philosophy — Principal Advisor

    Other advisors:

  • Doctor Philosophy — Associate Advisor

    Other advisors:

Completed Supervision

Possible Research Projects

Note for students: The possible research projects listed on this page may not be comprehensive or up to date. Always feel free to contact the staff for more information, and also with your own research ideas.

  • The yeast Saccharomyces cerevisiae is widely used in fermentation to produce wine, beer, and bioethanol. However, this well-researched microbe can also be efficiently engineered for the production of complex natural products. Well-known examples are the anti-malaria drug artemisinin are the ant-cancer drug paclitaxel.

    In this project, we are interested in the production of triterpenoids, the largest group in the natural product class. Many of these molecules have biological activities that make them promising candidates for pharma, nutraceutical, or cosme(ceu)tical applications.

    We have engineered a superior S. cerevisiae platform strain capable of the synthesis of diverse triterpenoids at the gram-scale level. In this project, we aim to expand the product spectrum to alpha-amyrin type triterpenoids with anti-ageing and anti-obesity properties that are used are investigated for use in cosmetics and pharmaceuticals.

    You will recombinantly express plant enzymes in the yeast chassis to enable the production of a few target products. You will further address a major bottleneck in the production of triterpenoids, the intracellular accumulation of the products, which results in cell toxification and low production efficiency. We are following alternative and complementary approaches including the expression of recently identified transporter, in situ extraction and optimization of the intracellular product trafficking route.

    You will gain in-depth knowledge on the metabolism of S. cerevisiae and practical skills in metabolic engineering and synthetic biology including, molecular biology, omics analyses, microscopy, fermentation, and analytics.

    Honours and (under)graduate students are welcomed to work on specific subprojects.

    Please contact me for further information.

  • Modern protein-based vaccines require adjuvants to improve immunogenicity and hence efficacy. The natural product class of triterpenoids includes molecules that have been shown to be very potent vaccine adjuvants. From these candidates, squalene and Quillaja saponins have been approved for their use in vaccines against flu, shingles and malaria. And many more triterpenoid-adjuvanted vaccines are in the pipeline.

    These molecules are currently sourced from animal and plant-derived sources. Squalene is found in high abundance in the liver oil from (deep-sea) sharks and currently the only approved source for medical applications. The Quillaja saponins contained in QS-21 adjuvants are only produced by specific trees in limited regions in South America. Both species, sharks and Quillaja saponaria, are threatened by overexploitation. With the increasing demand for potent vaccines, this is expected to increase.

    In this project, we are working on the biotechnological production of these compounds with engineered Baker's yeast Saccharomyces cerevisiae. We can produce squalene and QS-21 precursors at the gram-scale level, which is the current state of the art.

    Within this larger project, two HDR projects are available focusing on (a) improving squalene production and secretion of the intracellular storage molecule into the fermentation medium, and (b) implementing the complex QS-21 biosynthesis pathways in the yeast chassis.

    Honours and (under)graduate students are welcomed to work on specific subprojects.

    You will gain in-depth knowledge on the metabolism of S. cerevisiae and practical skills in metabolic engineering and synthetic biology including, molecular biology, omics analyses, microbiological work, fermentation, and analytics.

    Please contact me for further information.

  • Redox cofactors play a central role in the metabolism of living organisms. The most widely used cofactor is NAD(P)H. In the central carbon metabolism, the oxidised form NAD(P)+ is the primary acceptor for electrons from carbon oxidation. These electrons are then fed into the electron transfer chain, powering the respiratory system for ATP and thus energy generation. Although efficient, this system leads to CO2 formation via the oxidation of carbon metabolites and, hence, to CO2 emissions during biotechnological processes. In this project, we investigate alternative systems for NADH regeneration with electrons from sustainable energy sources, ultimately decoupling energy and carbon metabolism. Our focus lies hereby on hydrogenases. These enzymes use electrons from hydrogen to generate NADH instead of carbon metabolites, while hydrogen can be produced solely from water and electrons from renewable energy sources. Implementing efficient hydrogenase-based NADH regeneration systems in vivo should lead to more carbon-efficient and sustainable biotechnological processes for a greener bio-based future.

    We’re looking for a motivated student interested in carbon-efficient biological processes. The project offers options for working in molecular biology, bioprocess development, and robotics. Please get in touch with me for further information.

  • Research in the Eberg group is developing biotechnological production of valuable plant natural products in Saccharomyces cerevisiae, an established biotechnological workhorse. We are specifically interested in triterpenoids, plant natural products that find applications as high-intensity sweeteners, vaccine adjuvants or cosmetic ingredients and are heavily researched as novel drugs against cancer and other diseases. Our research is driven by the risk of overexploitation of rare plants for product extractions and a need to produce these valuable compounds at higher quantities with efficient and sustainable processes.

    Several student projects are available addressing the limitations of establishing triterpenoid production in S. cerevisiae.

    1. Enhancement of ER proliferation in Saccharomyces cerevisiae

    The project's primary objective is to enhance the amount of endoplasmic reticulum (ER) membrane in the yeast Saccharomyces cerevisiae through metabolic engineering. Triterpenoid synthesis is catalysed by ER membrane-bound enzymes, and our research showed that ER membrane availability limits their production. Building on these initial results, this project shall investigate optimal ER membrane proliferation to maximise productivity.

    Genes identified to affect ER proliferation shall be overexpressed or deleted in the yeast engineered for triterpenoid production. This project will expose the student to various molecular biology methods, including plasmid construction, yeast transformation, and CRISPR-Cas9 for gene deletions and insertions. To visualise the ER, fluorescent protein-tagged ER transmembrane protein will be expressed in engineered yeasts. Flow cytometry analysis and confocal microscopy will be employed to compare the ER size of engineered yeast strains and their reference, and the impact of ER size on triterpenoid production will be investigated.

    2. Interaction between ER size and broader metabolism of Saccharomyces cerevisiae

    Previous studies, which increased ER proliferation to boost triterpenoid production, indicate the manifestation of broader metabolic and phenotypic changes in the engineered yeast strains. To investigate the impact of organelle morphology on cellular biosynthetic pathways, this project will apply proteomics and transcriptomics analysis of strains with diverse ER and cellular phenotypes. The generated comprehensive omics dataset will then be analysed with computational methods to understand better the potential relationship between metabolic pathways and ER membrane proliferation in yeast. These analyses shall also identify innovative, novel engineering targets to augment ER proliferation and triterpenoid production.