Evolution of Symbioses: Understanding the Impact of Genetic Diversity through a Systems Perspective

Single celled, apicomplexan parasites such as Plasmodium, Toxoplasma and Cryptosporidium cause devastation and misery to millions worldwide. Despite their significance, few effective treatments are available; a situation that is likely to deteriorate with the emergence of new resistant strains of parasites. Our group’s research focuses on combining genomics with systems based methods to understand how genetic diversity contributes to parasite survival strategies and virulence. For example, we showed how strain variants of the coccidian parasite, Toxoplasma gondii, alter their metabolic capacity to affect growth and virulence potential and consequently exhibit differential susceptibilities to drug inhibition; findings with obvious implications for the design of global intervention strategies. In more recent work, we sequenced the genome of Sarcocystis neurona, a tissue-cyst forming member of the Coccidia and close relative of T. gondii, that is arguably the most successful single celled parasite genus in the world. Genome comparisons across the clade, including Eimeria, Neospora and Toxoplasma identified a variety of molecular innovations that have helped drive the transition from a purely enteric parasite dependent on a single host (Eimeria), to those able to invade the tissues of multiple intermediate hosts (Sarcocystis, Toxoplasma and Neospora). Through the identification of pathways that can be targeted for therapeutic intervention, these studies are laying the foundation for future drug development strategies.