The Reese Lab: What we study

Reese lab research images
We take an interdisciplinary approach to tackling tough scientific questions and combine molecular genetics, cell biology, and biophysics to deeply interrogate the mechanisms of signaling at the Toxoplasma-host interface.

What we care about:

Our lab is broadly focused on the cellular signaling that drives the interactions between the intracellular parasite Toxoplasma gondii and its varied hosts. Our goal is to understand how properties of individual parasite molecules enable the parasite to respond to its environment and even to co-opt its host cells. By viewing these molecules through an evolutionary lens, we hope to understand both how signaling networks can evolve new characteristics, and how host-pathogen competition can drive changes in disease outcomes.

How do we do it?

We use a variety of molecular genetics tools to manipulate the parasite and identify functions of proteins of interest. We use fluorescence and super-resolution techniques to gain an understanding of how the molecules alter both the parasite and its host cells. We combine biochemical and structural methods such as crystallography, NMR, and cryo-EM to determine the molecular mechanisms of action at the highest resolutions possible.

Some questions we are working on now:

  • How does Toxoplasma's arsenal of atypical effector kinases and pseudokinases protect it from the immune system and allow it access to host nutrients?
  • How do divergent parasite kinases regulate the maturation of the vacuole in which the parasite survives?
  • What are the critical control points in the parasite lytic cycle? What can this tell us about the architecture of parasite signaling networks and its evolution? Can we leverage this knowledge to identify small molecules that target these processes?
  • Because the parasite is genetically divergent from typical model organisms, the majority of Toxoplasma genes are refractory to bioinformatic functional predictions. We are working to use structural biology to help probe the biochemical functions of these molecules.

Why study Toxoplasma gondii?

Whereas most pathogens have a single or restricted range of hosts with which they co-evolve, the obligate intracellular parasite Toxoplasma gondii can infect virtually an cell of almost any warm-blooded animal. This is a remarkable feat – to remain a successful parasite, Toxoplasma has co-evolved with multiple diverse host species, from avians to mice and humans. Thus Toxoplasma is a superb system for the study of host-pathogen competition. Arguably, Toxoplasma is the most successful parasite in the world; around one in three humans are infected world-wide!

During infection, Toxoplasma secretes a large number of effector molecules into its host cell that alter diverse host processes such as cell cycle, apoptosis, and cytokine signaling. Toxoplasma strains that carry divergent alleles of these polymorphic effectors elicit radically different responses in host cells and thus cause distinct disease symptoms. One strain may kill a mouse but chronically and asymptomatically infect a bird; another second strain may do the reverse. We are working to uncover the mechanism for these differences, from the molecular and cellular to the organismal level.

If you find these types of questions engaging and might like to join, then please contact us.