Systems biology of acetogen gas fermentation

Dr Kaspar Valgepea

Due to the contribution of fossil-based industries to climate change, the world faces an increasing need for sustainable production of fuels and chemicals from renewable feedstocks. Recently, acetogen bacteria have attracted great interest as cell factories for converting inexpensive and abundant waste feedstocks (e.g. syngas [CO, H2, CO2], industrial waste gases) into high-value products using gas fermentation. Although acetogens arguably use the first carbon fixation pathway on earth to fix CO2, better understanding of metabolism is needed for their metabolic engineering. We have built a state-of-the-art gas fermentation facility and developed a systems biology platform for advancing the understanding and engineering of acetogen metabolism through building the first quantitative links between carbon, energy, and redox metabolism. We use steady-state cultivation coupled to gas, transcriptomics, proteomics, and metabolomics analyses to reconstruct acetogen metabolism in silico using genome-scale metabolic models. Our systems-level approach has led to the discovery of a growth-boosting nutrient, a novel regulatory mechanism for carbon distribution, and prevalence of post-translational regulation of acetogen metabolic fluxes.

Kaspar Valgepea is currently a Postdoctoral Research Fellow in the Nielsen/Marcellin group at AIBN leading the development of an integrated systems and synthetic biology platform to expand the product spectrum of gas fermentation. His research focuses on the integration of systems biology tools (e.g. proteomics, metabolomics, genome-scale metabolic modelling) with steady-state gas fermentation experiments for understanding and eventually overcoming the energetic limitations in acetogen metabolism. As the research project is in collaboration with a leading biotechnology company LanzaTech Inc., this systems-level approach has promise to enable rational metabolic engineering of acetogens for higher-value products. He obtained his PhD from Tallinn University of Technology for describing novel regulatory principles in Escherichia coli metabolism using systems biology. Prior to that, he was a Masters level researcher in Japan and a Visiting Scholar in the biotechnology company Genomatica Inc. His work has been published in several top journals of the field.


Nanoparticle-facilitated combination cancer therapy

Dr Li Li

Cancer remains one of the world’s most devastating diseases, with more than 10 million new cases every year. Chemotherapy is one of most common cancer treatments in clinics. 5-fluorouracil (5-FU) is one of the first line drugs used in cancer treatment, either alone or in combination with other drugs. However, the response rate of 5-FU based treatment is still less than 60% due to the low concentration of drugs at tumour level and adverse side effects. 
With the rapid development of nanotechnology, nanoparticle-based drug carriers have emerged as effective tools for targeted drug delivery in cancer therapy, and greatly improved the treatment effectiveness. Layered double hydroxides (LDHs), a family of anionic clay materials, can efficiently deliver anionic anticancer drugs (e.g. 5-FU) and siRNA into the cells to enhance the cytotoxicity of drugs to cancer cells. Based on our previous research, we have recently developed 5-FU-based therapies combined with siRNA or other anticancer drug mediated by LDHs. These combination therapies significantly inhibited the tumor growth in vitro and in vivo with significantly reduced drug doses. We have also investigated the mechanism of combination therapies delivered by LDHs. 

Li Li is a Research Fellow at Australian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland (UQ).  She received her PhD in Chemical Engineering from China University of Petroleum. She worked as Postdoctoral Research Fellow at AIBN, UQ and School of Chemical Engineering, University of New South Wales. In 2011, she was awarded a UQ Postdoctoral Research Fellowship and joined Professor Zhiping Xu’s group at AIBN. Currently, she holds an Advance Queensland Research Fellow (Mid). Her research interest focuses on engineering nanoparticles for targeted drug/gene delivery and oral vaccine delivery for cancer therapy and animal health control. Recently, she has developed nanoparticle-mediated combination therapy to enhance the effectiveness of chemotherapy for breast cancer and colon cancer. She has also built strong linkages with agricultural industries to develop functional nanomaterials as carriers for drug and vaccine delivery to solve the practical problems in animal health. Her research performance has been recognised with the award of Wilston Churchill Fellowship, QLD International fellowship and ATSE Early Career Fellowship.

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