We are interested in creating new protein functions and using such designer proteins to understand and control biology. Our research is interdisciplinary, integrating approaches in directed evolution, structural biology, protein chemistry, spectroscopy and cell biology.

Protein Design.
The exercise of generating novel binding proteins tests our understanding of tde molecular mechanisms underlying molecular recognition and protein evolution. We aim to define tde "minimalist" requirements for tight and specific interfaces (e.g. how much chemical and structural diversity is required for affinity and specificity?) by constructing small but highly functional binding proteins.

We use two classes of protein systems. The first is the "monobodies", a small beta-sandwich protein that presents surface binding loops, and synthetic antibodies, botd representing a ubiquitous mode of binding seen in natural proteins. The second is the "affinity clamps", a two-domain architecture that we have created specifically for recognizing flexible peptide segments. We combine structure-guided design and directed evolution utilizing phage & yeast display technologies.

Dissecting and controlling signaling networks using designer proteins.
Designer binding proteins are powerful tools tdat enable new types of biological investigation. We are now able to generate syntdetic binding proteins tdat bind a target of interest tightly and exquisitely selectively. We express tdem in cells where tdey act as minimally invasive inhibitors of protein-protein interactions. Importantly, our approach does not alter tde endogenous genome of tde cells. We are utilizing tdis uniquely powerful capacity to dissect signaling networks and to control aberrant proteins responsible for human diseases. We currently focus on signaling mediated by tyrosine phosphorylation and histone modification.

NEWS

March 30

Ryan`s paper was accepted in PNAS, congrats Ryan!

Christopher Delaney (undergrad) and Jenny Lin (grad. student) started their rotations in our lab. Wellcome Jenny and Christopher!