Cryo-tomography captures the fascinating infection organelle of tiny parasites

How do these findings contribute to your research area?

The polar tube has been studied for many decades. It is known to be composed of several proteins but no structural information on the proteins and their interactions to form the tube is available to date. This is a huge challenge as the polar tube is the primary mode of infection of these parasites and thus limits any mechanistic studies into how polar tube proteins enable elastic changes in the tube for invading host cells. Our work makes important advances in this field by providing first in situ structural insights into the remodeling of the polar tube protein layers when infectious material is injected into the host cells. Additionally, the unique state of hibernating ribosomes captured inside the tubes presents a unique organization and mode of ribosome regulation parasites and, likely in all eukaryotes. 

What was the exciting moment during your research?

This is one of the first instances of utilizing cryo-ET to study microsporidia pathogens. Hence there were several AHA!! moments during our experiments and data analysis stages. One of the most exciting instances occurred when we discovered the regularly arranged pattern of particles in the polar tubes and this immediately set us on a path to identify them using subtomogram averaging. Though performing this analysis was much more difficult than we initially anticipated, but when we discovered that the particles were ribosomes locked in an inactive state, it immediately excited us to understand the biological relevance of these regular packing. Similarly, the changes observed in polar tube proteins also got us extremely captivated in understanding how the tube changes in response to the presence of infectious material during transport. 

What do you hope to do next?

For me, this is just the beginning. I aim to follow up on this work by pursuing high-resolution structural studies on individual polar tube proteins. This approach will help us assemble the larger puzzle i.e., the polar tube, and understand the transitions in individual proteins that aid infection, using high-resolution structural studies. In the long term, my objective will be to develop inhibitors of polar tube firing and remodeling to help fight infection in humans, important livestock, and pollinators. 

Where do you seek scientific inspiration from?

I enjoy reading very broadly in areas ranging from life science to technology, and other allied subjects. It’s always good to cross-pollinate ideas and get inspiration from the works of others about solving challenges we face in our experimental systems. 

How do you intend to help Indian science improve?

Any contribution to a subject area is expected to collectively uplift the science, paving the way for newer and more challenging questions. In the Indian context, microsporidia are severely underreported and rarely studied despite clinical reports of infection in both immunocompetent and immunosuppressed patients. Further, microsporidia infections pose a great threat to agricultural sectors like the silk industry, fishing, and honeybee farming. My next efforts will be to bring in my expertise with these organisms and structural methods to uncover their prevalence and infection mechanisms.