Mechanism of invasion in microsporidia parasites

Microsporidia are unicellular parasites closely related to fungi. Over 1400 microsporidia species have been reported, which infect a wide range of hosts from invertebrates like silkworms to humans. Microsporidia infections can be fatal in  immunocompromised patients. Due to the diverse animals they can infect, microsporidia have also been implicated in honeybee colony collapse, decreased yield in farmed seafood such as shrimp, and have negative impacts on many other agriculturally important animals. Consequently, understanding how microsporidia infect their hosts will have broad applications, both for the treatment of disease as well as the agricultural and biotechnology industries. 

Our lab investigates one of the earliest steps in the infection process. To gain entry into host cells, microsporidia employ a fascinating harpoon-like organelle known as the polar tube. The polar tube sits as a tight coil inside the dormant spore. Under suitable environmental conditions, the tube is released from the spore and can extend to be ~20 times the length of the spore, facilitating transport of infectious cargo from the spore to the host cell. The polar tube firing process occurs extremely rapidly, on a millisecond timescale, and the mechanism by which the polar tube organelle initiates infection is not well understood.

In our lab, we use a multi-scale imaging approach to visualize and tease apart the mechanism of infection. Techniques include optical microscopy, structural cell biology, cryo EM, X-ray crystallography, biochemistry and cell biology.  

Questions we are currently addressing include:

1. What are the dynamics of polar tube firing across different microsporidia species? What can this tell us about host-cell specificity? 

2. What are the biochemical and structural properties of the polar tube that allow it to undergo an enormous conformational change during the firing process?