The goal of metabolic and cellular engineering is to endow novel and useful properties to cellular systems. Recent advances in molecular biology and genetic engineering empower metabolic engineers with an increasing ability to create any desired cellular modification. The integration of these approaches with an ever-increasing database of knowledge about these cellular systems (due in part to genomic sequencing efforts) provides an unprecedented opportunity to engineer cellular systems. Our research group focuses on the integration and implementation of these tools and knowledge for the design, production, and elicitation of phenotypes relevant to biotechnological processes and medical interest.
Using a variety of host systems including microbial (eg. Escherichia coli), fungal (eg. yeast), and mammalian (eg. Chinese Hamster Ovary (CHO) cells), we seek to develop the necessary genetic tools and methodologies for creating industrially-relevant organisms for biomolecules, biofuels, and biopharmaceuticals. To accomplish this task, traditional pathway engineering will be utilized in conjunction with novel tools for introducing genetic control (such as global Transcription Machinery Engineering, promoter libraries, and gene mutagenesis).
Overall Research Goals:
To develop new strategies and tools for the engineering and cultivation of cellular systems applicable to both eukaryotic and prokaryotic systems
To develop suitable host strains (both mammalian and microbial) for the high level production of value-added products and bioactive molecules
To understand and engineer complex cellular phenotypes, including disease states, in an effort to identify novel genetic targets
To develop molecular biology tools which allow for both tunable and combinatorial control of gene expression and regulatory networks
To develop strategies for engineering cellular systems through protein engineering and evolution
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.
