José L. Avalos

Photo of Jose Avalos
Associated Faculty, Chemical and Biological Engineering and the Andlinger Center for Energy and the Environment

Contact

javalos@princeton.edu
609-258-9881
Hoyt Chemical Laboratory, 101
Avalos Lab

Research Area

Biochemistry, Biophysics & Structural Biology

Research Focus

Metabolic engineering, organelle engineering, synthetic biology, structural biology, and protein engineering
We engineer organisms with new desirable traits to address challenging problems in human health, sustainable energy, industry, and the environment. Our research interests span metabolic engineering, organelle engineering, synthetic biology, structural biology, and protein engineering.  We take a two-pronged approach to our research. On one hand, we engineer cells forging established methods with new technologies developed in the lab. On the other, we address fundamental questions of protein structure and function, cellular physiology, and metabolism that either currently limit our capabilities in cellular engineering, or that offer opportunities for new technologies. These two facets of the lab complement and fuel each other, as technological developments give rise to new fundamental questions, and basic research opens avenues for new technologies.

Metabolic Engineering

Metabolic engineering is the application of genetic engineering to modify and optimize the metabolism and regulatory systems of an organism to produce or degrade a desired compound. We are currently focused on engineering microorganisms (mostly yeasts) for two possible goals: 1) to produce molecules of commercial value, such as biofuels, bioplastics, commodity chemicals, or specialty chemicals (drugs, pigments, flavorants, etc.) from renewable sources, including cellulosic biomass; or 2) to degrade or remove contaminants from the environment (bioremediation).

Organelle Engineering

Subcellular engineering is a fast-growing field in bioengineering, in which metabolic pathways or other synthetic functions are targeted to specific cellular organelles to take advantage of their unique environments, metabolites, and enzymes, as well as their physical separation from the cytosol. We are particularly interested in mitochondrial engineering, where we have shown that targeting metabolic pathways to yeast mitochondria is an effective way to enhance the productivity of engineered pathways. In addition, we are interested in engineering the mitochondrial physiology to enhance metabolic pathways targeted to this highly dynamic, and versatile organelle.

Synthetic Biology

Synthetic biology combines molecular biology, genetic engineering (including genome editing), directed evolution, biophysics, computational biology, and protein engineering, aiming to generate synthetic phenotypes (analogous to synthetic chemistry aiming to generate synthetic molecules by designing series of chemical reactions). We are particularly interested in developing biosensors and regulatory genetic circuits applicable to metabolic engineering. Biosensors are useful to measure, monitor, screen, or select for desired functions (either natural or engineered). Genetic circuits are useful to control engineered metabolisms and other engineered functions in the cell.

Structural Biology and Protein Engineering

Our efforts in synthetic biology and metabolic engineering are complemented by fundamental studies on the molecular structure and function of the proteins involved, such as enzymes, transmembrane transporters, receptors, and transcription factors. To study these proteins in molecular detail, we use different biophysical and biochemical methods, including X-ray crystallography. Understanding the relationship between the structure and function of these proteins significantly enhances our ability to engineer them with new functions relevant to metabolic engineering or synthetic biology.