Chemical, biological, and biophysical projects inspired by the process of evolution

Antibiotics

The arylomycins inhibit SPase, which is required for protein secretion - but many bacteria have naturally evolved resistance. We're developing arylomycins that overcome this resistance and looking for other latent antibiotics.

Genetic Alphabet

We've surpassed our longstanding goal of developing a replicable unnatural DNA base pair and are now focused on not just storage, but also retrieval of information in an expanded genetic alphabet in vivo.

SELEX

We've evolved polymerases that accept non-natural substrates, e.g. unnatural or modified natural R/DNA. Recent work has focused on applying this progress to the evolution of nuclease-resistant aptamers.

Biophysics

We're characterizing antibodies at different stages of their evolution to examine how somatic mutations affect dynamics and function. We're also developing the use of carbon-deuterium bonds as general probes of protein dynamics.


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Antibody dynamics as a function of evolution

Zimmermann, PNAS 2006

E. coli with an expanded alphabet

Zhang, PNAS 2017

C–D bonds detect N–H--N H-bond

Adhikary, JACS 2014

Initial characterization of ayrRABC

Craney, mBio 2015