Research

Our group focuses on engineering biology to produce organic molecules of interest such as biofuels, commodity and specialty chemicals, and protein pharmaceuticals.  To accomplish these tasks, traditional pathway engineering approaches are merged with novel synthetic biology tools, protein engineering strategies, systems biology paradigms and applied genetic engineering capabilities.

 research

We utilize a variety of host systems including microbial (eg. Escherichia coli), fungal (eg. the yeasts Saccharomyces cerevisiae and Yarrowia lipolytica), and mammalian cells (eg. Chinese Hamster Ovary (CHO) cells and Human HEK293) to produce a diverse array of products.  Specifically, our lab focusses on developing the methodologies and tools for altering cells and “hijacking” basic metabolism.  The goal is to “rewire” cellular systems into industrially-relevant biochemical factories.  In doing so, we are heavily invested in developing novel synthetic biology and directed evolution approaches aimed at increasing our capacity to engineer cells.

Overall Research Goals:
  • To develop suitable host strains for the high level production of value-added products and bioactive molecules
  • To develop new synthetic biology tools and strategies for controlling transcription, translation, and regulation in both eukaryotic and prokaryotic systems
  • To merge protein engineering strategies with pathway engineering to globally "rewire" cellular systems
  • To develop molecular biology tools which allow for both tunable and combinatorial control of gene expression and regulator networks
  • To develop high throughput strategies for rapidly screening improved phenotypes
  • Microbial Engineering
    (e.g. Escherichia coli)
    Microbial systems, such as E. coli, serve as excellent model and industrial platforms for the production of both bulk and commodity small molecules. Products such as carotenoids, amino acids, and organic acids can all be made at high quantities in microbial hosts. In this research program, microbial systems will be explored as a host for producing novel small molecules. Additionally, new tools for imparting global perturbations (such as global Transcription Machinery Engineering) will be tested. Finally, this system will be used to develop novel tools for controlling and altering metabolic pathway throughput.
    Fungal Engineering
    (e.g. Sacchromyces cerevisiae and other yeasts)
    Fungal systems, including yeasts such as S. cerevisiae, have the potential to revolutionize the biofuels industry. Since the ancient times when wine making began, yeasts have been exploited for their potential to convert sugars into ethanol. In this research program, both standard and industrial yeasts will be engineered to produce both "traditional" biofuels such as ethanol and "non-traditional" or novel molecules which can be used for transportation fuels. Furthermore, this system will be used to develop novel tools for (1) introducing genetic control of essential genes and (2) improving cellular/metabolic throughput.
    Mammalian Cell Engineering
    (e.g. Chinese Hamster Ovary Cells)
    Mammalian cell cultures are a major platform of choice for most large protein biopharmaceuticals (especially for glycosylated proteins). While the cell culture and processing conditions have been long studied, little attention has been placed on the cellular and metabolic engineering of these systems. In this research program, genetic tools will be developed for controlling the expression of transgenes. Furthermore, these tools will be expanded by creating methodologies for creating large-scale genetic perturbations to elicit global phenotypes of importance to these systems. Finally, traditional pathway engineering and protein engineering will be invoked to improve the function and requirements of these cells during the culturing phase.