Laboratory for High-Throughput Mechanistic Biochemistry & Molecular Evolution
University of California, Berkeley
We study why proteins are the way they are—how they adapt, how they are regulated, how they fail in disease, and how understanding these constraints enables us to target and engineer them.
About the Lab
Life is built on proteins. Nearly every biochemical reaction, metabolic pathway, signaling decision, and cellular behavior depends on protein properties shaped by evolution under specific environmental conditions. When those constraints are challenged—by mutation, environmental change, or chemical perturbation—biological systems can adapt, fail, or discover new modes of function or regulation. Understanding these outcomes requires quantitative measurements that connect molecular properties to biological behavior.
Our lab studies biomolecules at their limits. We investigate how physical law, environmental context, and evolutionary history shape molecular function, and how pushing against these constraints gives rise to drug resistance, disease-causing mutations, and molecular regulation. By combining high-throughput biochemistry and biophysics using microfluidics, cellular assays, and modeling, we build quantitative maps that reveal which molecular solutions are robust, which are fragile, and which emerge only under strong selective pressure.
What we do
How do physical constraints shape molecular function across sequence and environment?
We map constrained molecular landscapes to reveal how sequence, environment, and biophysics jointly determine activity, regulation, and dynamics.
How is protein function regulated—and how does allostery emerge?
We study how biomolecules sense, transmit, and integrate signals through regulation and allostery, linking molecular interactions and conformational dynamics to function.
What happens when proteins are pushed beyond their limits?
We investigate how perturbations such as mutations, drugs, and environmental change drive adaptation, resistance, or failure, interrogating the molecular origins of evolution, disease, and drug resistance.
What are protein sequence models actually learning?
We use experiments to dissect what modern protein models capture—and miss—about biomolecular function, separating physical law from evolutionary history with the goal of building constraint-aware, predictive models.
How can we quantitatively interrogate protein function at otherwise inaccessible scale and complexity?
We develop high-throughput biochemical and biophysical technologies that enable quantitative measurements for challenging biomolecular systems across thousands of variants and conditions.
