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Alper, Hal

Hal S Alper

Department of Chemical Engineering

Z. D. Bonner Professorship of Chemical Engineering


Phone: 512-471-4417

Office Location
CPE 5.408

Postal Address
AUSTIN, TX 78712

Our reserach focuses on engineering biology to produce biomolecules, biofuels, and pharmaceuticals using the tools of metabolic engineering and synthetic biology. The overall 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).

Our 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

Generalizing a Hybrid Synthetic Promoter Approach in Yarrowia lipolytica (2013) Applied Microbiology and Biotechnology 97(7), 3037-3052

Metabolic Engineering of Muconic Acid Production in Saccharomyces cerevisiae (2013) Metabolic Engineering 15(1), 55-66.

Directed evolution of xylose isomerase for improved xylose catabolism and fermentation in the yeast Saccharomyces cerevisiae. (2012) Applied and Environmental Microbiology

Linking yeast Gcn5p catalytic function and gene regulation using a quantitative, graded dominant mutant approach. (2012) PLoS ONE 7(4), e36193.

Controlling promoter strength and regulation in Saccharomyces cerevisiae using synthetic hybrid promoters. (2012) Biotechnology and Bioengineering

A molecular transporter engineering approach to improving xylose catabolism in Saccharomyces cerevisiae (2012) Metabolic Engineering 14(4), 401-411.

Re-engineering Multicloning Sites for Function and Convenience (2011) Nucleic Acids Research, doi: 10.1093/nar/gkr346.

Functional Survey for Heterologous Sugar Transport Proteins, using Saccharomyces cerevisiae as a Host (2011) Applied and Environmental Microbiology 77, 3311–3319.

Linking high resolution metabolic flux phenotypes and transcriptional regulation in yeast modulated by the global regulator Gcn4p (2009) PNAS 106, 6477-6482.

Engineering yeast transcription machinery for improved ethanol tolerance and production (2006) Science 314, 1565 - 1568.

Construction of lycopene-overproducing E. coli strains by combining systematic and combinatorial gene knockout targets (2005) Nature Biotechnology 23, 612 - 616.