Our Research

We are curious about how proteins perform a variety of functions at the molecular level and at the level of the whole animal. Our current interests include:

Project 1: Mechanism of Assembly of Vg1-Nodal heterodimers

Two signaling proteins, Vg1 (aka Gdf1/3) and Nodal, function as a heterodimer unit to specify the mesoderm and endoderm, which gives rise to animal tissues such as muscle, bone, and blood. The formation of heterodimers is tightly regulated. For example in early zebrafish embryos, sequence motifs of Vg1 that could bind to protein folding chaperones promote its retention as a monomer in the cell – at least until Nodal comes along. How does Nodal overcome these retention factors in order to bind to Vg1? What are the structural determinants that allow the robust formation, secretion, and potent activity of Vg1-Nodal heterodimers?

Project 2: New enzymes for processing of natural and disease-causing proteins

We are expanding our library of synthetic enzymes via saturation mutagenesis, directed evolution, and machine learning to recognize and cleave a variety of secreted proteins. Partnering with computational biologists and biochemists, we plan to synthesize de novo enzymes experimentally and in silico to further accelerate library generation. These new enzymes will be employed in the controlled cleavage of secreted neuropeptides that modulate animal behavior, as well as in the degradation of pathological proteins in neurodegenerative disorders.

Project 3: CRISPR/Cas-based tools to manipulate multicellular signaling

Cells receive environmental signals through cell-surface receptors that can induce programmed responses such as cell migration, differentiation, division, and even death. We aim to create user-defined cell responses to external stimuli using the CRISPR/Cas system, which can target specific gene(s) and modulate its expression at will. Toward this goal, we have successfully patented a molecular tool that integrates the CRISPR/Cas system with synthetic or naturally occurring receptors. We are now looking to test this novel tool in various biological contexts in vivo.