Research

Research

Our Lab Research


FIGURE 1: Yeast display is a robust, quantitative approach
to protein engineering.



FIGURE 2: Examples of noncanonical amino acids that can be
genetically encoded in proteins produced in the yeast
Saccharomyces cerevisiae.



FIGURE 3: Cancer cells coopt many aspects of their
surroundings as tumors progress.



FIGURE 4: Construction of protein-small molecule hybrids
on the yeast surface.

The Van Deventer Laboratory applies chemical biology and biomolecular engineering techniques in search of new reagents and therapeutics, primarily for applications in targeting and disrupting the tumor microenvironment. We have established a platform combining yeast display (Figure 1) with noncanonical amino acids (Figure 2) that will enable us to explore unique strategies for developing highly specific enzyme inhibitors and other therapeutic leads relevant to the biology of the tumor microenvironment. We are also actively pursuing technology development centered around improving noncanonical amino acid incorporation strategies in yeast and multiplexed screening with yeast display.

Cancer targeting. A growing body of evidence suggests that tumor cells are able to coopt their surroundings in order to promote tumor progression (Figure 3). We are interested in developing strategies for precisely disrupting the individual processes within the tumor microenvironment that lead to disease progression. Selective interference with a single process in this complex environment requires exquisite selectivity, especially when the molecular targets come from families of closely related enzymes or receptors. Although antibodies and other binding proteins can discriminate between closely related proteins, the identification of binding proteins that disrupt biologically relevant enzymatic and signaling events remains challenging. We are investigating two therapeutic engineering strategies in this area:

  1. Noncanonical amino acid-compatible yeast display for the discovery of protein-small molecule hybrids (Figure 4) that simultaneously exploit the best properties of proteins and small molecules.
  2. Conventional yeast display-based strategies for identifying proteins that disrupt biological activities in high throughput.

Technology development. Ongoing work in the laboratory aims to enhance genetic code manipulation strategies and streamline yeast display-based screening efforts. Underlying many of our efforts are strategies that enable noncanonical amino acids to be genetically encoded in proteins. We seek to learn the fundamental principles governing efficient noncanonical amino acid incorporation in Saccharomyces cerevisiae and engineer improved noncanonical amino acid incorporation systems. We anticipate that upgrading these platforms will provide new opportunities for pursuing applications in protein-small molecule hybrid discovery, materials development, biocatalysis, and other areas. High throughput screening with yeast display is another key aspect of our work. We are currently pursuing strategies for multiplexing yeast display using simple manipulations that can be performed at the benchtop. Successful multiplexing efforts will enable the discovery of reagents and therapeutics for a wide range biological targets in parallel.