Our lab is interested in many diverse, basic, and unresolved problems in molecular evolution:

• What are the mechanisms by which new functions evolve?

• What are the physical constraints on protein evolution?

• How can we reliably distinguish distant homology from convergence in structurally similar protein domains?

• How do substitutions distal from the active site affect catalytic activity?

• Are ancestral enzymes functionally promiscuous? Does specificity increase during evolution?

• To what extent is evolution adaptive or due to chance events?

• How many substitutions are required for evolution of a new function?

• Do novel functions evolve by small or large increments?

• How "reversible" are evolutionary trajectories? Does the order of substitutions matter?

• What is the importance of correlations among mutations (epistasis)?