For decades, researchers around the world have been investigating the molecular mechanisms by which microbes cause pain. Abhay Satoskar, a parasite immunology researcher at Ohio State University, is interested in the opposite question: How can a microbe relieve pain?

More specifically, Satoskar wants to explore the relationship between mammalian hosts and Leishmania mexicana, a unicellular parasite that causes chronic but surprisingly painless skin lesions. In a study published in iScience, Satoskar and his colleagues identified changes in host cell metabolism that may underlie these analgesic effects.¹

“It is fascinating to learn how this bug is evading host detection by manipulating not only the immune system, but in this case, even the sensory system,” said Satoskar.

By using mass spectrometry, his team measured differences in metabolites between infected and noninfected tissues in a mouse model of the disease. They found that L. mexicana infection altered purine metabolism at the lesion site; some of the upregulated purine metabolites, including xanthine, hypoxanthine, and inosine, are thought to play relevant roles in anti-nociception. Researchers also identified enrichment of certain pain-numbing endocannabinoid metabolites.  

“There is still a lot to explain,” said Ricardo Silvestre, an immunometabolism researcher at the University of Minho who was not involved in the study. “The work was mainly descriptive, and they are very honest in the paper about the limitations of the study. [However], I believe it opens a new field of research that many will follow.” 

One major limitation—the use of a mouse model—Satoskar hopes to remedy soon by validating these findings in human L. mexicana lesions. He also wants to dig deeper into the mechanisms governing infection-related shifts in these metabolic pathways, and noted that elucidating how L. mexicana manipulates nociception could have far-reaching effects. “If we find the mechanism—let's say a parasite molecule—it could be an important pain killer that could be used for other diseases,” said Satoskar.

         

In 2014, I was in the final year of my graduate studies in biophysicist Christoph Schmidt’s group at the University of Goettingen. I had collected decent data from my project investigating the mechanical properties of Drosophila embryos, so my advisor encouraged me to present at an international conference in Boston that summer. 

The day of my poster presentation, I had spare time before my session. Feeling well prepared for the event, I explored the beach before heading to the conference venue. When I entered the presentation hall, I noticed two shocking details. First, most attendees were dressed in formal clothes, while I stood there in my shorts and flip flops. Second, and much worse, there were no poster stands in sight; instead, a giant screen stood at the front of the room. That’s when I pieced together that my work had been selected for an oral presentation, not a poster. 

Mortified about how I had missed this detail in the acceptance email, I experienced both cold and hot sweats simultaneously. I realized that I could flee the situation or face it, and decided in favor of the latter. I rushed to my hotel, grabbed my laptop, and loaded the digital version of my poster. When it was my turn to present, I projected the poster on the screen, zooming in and out of sections as I spoke. The situation felt awful at the time, but I survived. I even got asked a few questions at the end of my talk. 

Thankfully, my advisor found the situation amusing rather than upsetting. Another silver lining of my debacle was that it served as an excellent networking catalyst; people recognized me as the “poster guy” for the rest of the conference. 

Although the incident was embarrassing, I learned that there’s always a way to go on. Scientific presentations seem like a big thing as a student, but in the end, this problem wasn’t as catastrophic as it seemed. 

This interview has been condensed and edited for clarity.

         

“My dear sir,” wrote botanist Thomas Andrew Knight in 1806. “It can scarcely have escaped the notice of the most inattentive observer of vegetation, that in whatever position a seed is placed to germinate, its radicle invariably makes an effort to descend towards the center of the earth.”¹

More than two hundred years later, attentive observers of vegetation are still working out the molecular mechanisms involved in this process. One of the first major discoveries—the identification of statocytes—occurred in the early 1900s.² These cells located in root tips contain heavy, starch-filled granules called amyloplasts that settle to the bottom of the cell. However, said Sophie Farkas, a molecular physiologist at the University of Freiburg, the molecular mechanisms that amyloplasts use to signal which way is down have only recently been elucidated.

     

In 2023, researchers found that tipping a plant 90 degrees triggered phosphorylation of proteins called LAZY.³ This caused the LAZY proteins to hop from the cell membrane onto the amyloplasts. Then as the amyloplasts slowly sedimented to the new bottom of the cell, they brought the LAZY hitchhikers with them. When the amyloplast reached its destination, the LAZY proteins hopped off and attached themselves to the membrane on the lower side of the cell.

“From there, we know that the LAZY proteins recruit other proteins,” said Farkas. Eventually, this leads to recruitment of PIN-FORMED 3 (PIN3), a transporter for the growth-regulating hormone auxin. Subsequently, auxins move to the lower side of the root, where they inhibit growth. If the root is positioned horizontally and grows faster on the upper side than on the lower side, the root is forced to curve downwards, toward the center of the earth.

Studying the mechanisms that control the growth and structure of roots may help scientists figure out how to engineer plants that are more drought resistant.