Ribozymes and their fitness landscapes. To understand the course of evolution, we need to characterize the basic features of fitness functions in sequence space. We study 'fitness' functions of macromolecules such as ribozymes for three reasons: 1) they occupy a relatively limited sequence space, 2) fitness is a direct result of their chemical properties, and 3) they may represent the primordial organisms of the RNA world.

Bacteriophage and the host spectrum. Why are parasites so specific for their host species, when expansion of the host spectrum could greatly increase the reproductive fitness of the parasites? We have been unlucky enough to witness just such an expansion in the host spectrum of SIV, which gave rise to HIV. Is the evolution of parasites constrained by the physical properties of their proteins? To tackle this problem, we study the host spectrum of bacteriophage by experimental evolution. Understanding the host spectrum of phage is also an exciting area from a medical perspective, because of the potential to use phage to fight bacterial infections.

Vesicles and primitive chemotaxis. Vesicles made of very simple amphiphilic molecules can show surprisingly interesting behaviors, including growth and division cycles and Darwinian competition. In the prebiotic world, protocells capable of directional movement could have a significant advantage. We study how the energy stored in external chemical gradients might be used to move vesicles in an anisotropic manner.

Replication in silico. How long can your genome be? If the mutation rate is too high, the fittest sequence cannot survive because mutation constantly disrupts the genotype (the Eigen 'error catastrophe'). This relationship between mutation rate and genome length could have been problematic for the very first organisms, which likely had high mutation rates. Using theory and simulation, we explore how this relationship may be modified by including realistic properties of the replicating system.