Research
 research

The Alper Lab rewires cellular metabolism to produce next-generation biochemicals, polymer precursors, fuels, and pharmaceuticals. In doing so, we are addressing global challenges including sustainability, human health, circular bio-economies, and clean energy/energy security. We rewire cells by uniquely merging the areas of synthetic biology, directed evolution, and pathway engineering. To complement these efforts, we have developed many synthetic genetic toolkits, high-throughput screening techniques, evolution schemes, and culturing platforms. Our mission is to enable advanced biomanufacturing using rewired host organisms.  

Synthetic Biology
We are developing new techniques for synthetic biology including transcriptional control elements, high-throughput CRISPR-enabled libraries, synthetic genetic circuits, and other tools that enable a newfound control of biological systems. We have developed many promoter and terminator libraries in conventional and non-conventional organisms with a focus on minimal and orthogonal sequence design.
Representative Examples:
research

Deaner and Alper, 2017. Systematic Testing of Enzyme Perturbation Sensitivities via Graded dCas9 Modulation. Metabolic Engineering. Link to paper

Morse, et al., 2017. Yeast terminator function can be modulated and designed based on predictions of nucleosome occupancy. ACS Synthetic Biology. Link to paper

Redden and Alper, 2015. The development and characterization of synthetic minimal yeast promoters. Nature Communications. Link to paper

Directed Evolution and High-throughput Technologies
We are establishing approaches for sensor-directed evolution and continuous evolution systems and apply these techniques to the engineering of transporters, regulatory proteins, and pathway enzymes. In addition, we work on utilizing microdroplet technologies to speed and automate the design-build-test cycle.
Representative Examples:
research

Wagner, et al., 2018. A comparative analysis of single cell and droplet-based FACS for improving production phenotypes: riboflavin overproduction in Yarrowia lipolytica. Metabolic Engineering. Link to paper

Abatemarco, et al., 2017. RNA-Aptamer-In-Droplet (RAPID) High-Throughput Screening of Secretory Phenotypes Nature Communications. Link to paper

Crook, et al., 2016. in vivo continuous evolution of genes and pathways in yeast. Nature Communications. Link to paper

Platform Strain Engineering
We are creating platform strain organisms for the high-level production of natural products, polymer precursors, and alternative fuels with a focus on utilizing non-conventional organisms and low-cost feedstocks. As examples, we have created organism suitable for high titers of lipids/fatty acids, polyketides, fatty alcohols, and organic acids. These products are suitable for nutraceuticals, specialty chemicals, monomers for polymerization, and as biofuels. We have also applied these strain engineering strategies for the conversion of lignocellulose-derived sugars and other waste carbon streams.
Representative Examples:
research

Cordova, et al., 2019. Direct production of fatty alcohols from glucose using engineered strains of Yarrowia lipolytica. Metabolic Engineering Communications. Link to paper

Markham, et al., 2019. Rewiring Yarrowia lipolytica toward triacetic acid lactone for novel materials generation. PNAS. Link to paper UT Press Release

Blazeck, et al., 2014. Harnessing Yarrowia lipolytica lipogenesis to create a platform for lipid and biofuel production. Nature Communications. Link to paper 2014 UT Press Release 2015 UT Press Release

Unique Biotic-Abiotic Interfaces
We are establishing microbe-laden hydrogel inks that enable preservable, on-demand production of chemicals and medicines. These systems can uniquely allow for stable co-culture maintenance.
Representative Examples:
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Johnston, et al., 2020. Compartmentalized microbes and co-cultures in hydrogels for on-demand bioproduction and preservation. Nature Communications. Link to paper UT Press Release