Single-celled parasites slip into the body unnoticed, in a drop of contaminated water, a morsel of undercooked meat, or a speck of dirt under a fingernail. Parasites have settled into dark, nutrient-rich intestines of nearly half of the world’s human population. 

When scientists study these parasitic infections in the lab, they cannot mimic what actually happens in the human intestine, stunting their ability to test antiparasitic drugs. Microbiologist Hanen Baggar is changing that. 

A PhD candidate in the University of Minnesota College of Veterinary Medicine’s Comparative and Molecular Biosciences Graduate Program, Baggar is working in the O’Connor Lab, coaxing stem cells into becoming the unique types of cells that make up the intricate human intestine. 

“Essentially we can create a miniature gut in a dish,” Baggar says. 

That miniature gut is called an organoid, a tiny, simplified three-dimensional lab-grown tissue that mimics the structure and function of a real human organ. This differs from traditional cell culture models, which use cells in a flask that cannot mimic how the gut functions, nor how parasites infect the intestinal system. Baggar’s is something called an apical-out organoid model. 

The mammalian gut has two main tissues: apical and basal. The apical side lines the inside of the intestine—where bacteria and parasites live—and absorbs nutrients. The basal, or outer side, houses the organ’s blood vessels and immune cells. When scientists grow organoids, the basal side is facing out. That means that anything they add to the culture––which is meant to mimic an organ––is applied to the opposite side as it would be in a real person. Baggar has found a way to culture an organoid in which the apical side faces out. 

“This gives the parasite a chance to infect that apical side directly, which is what happens in the real world,” she says. 

Baggar is using her model to research a parasite called Cryptosporidium parvum, which causes diarrheal illness that can be fatal for children and people who are immunocompromised. Ultimately, Baggar’s goal is to use the model to better understand how both the parasite and its host––in this case, a person’s immune system and intestinal cells––behave early on in infection. This will allow teams to better develop anti-parasitic drugs that target the infection. 

“This model is particularly useful for cryptosporidium infections because these parasites naturally infect the intestinal cells,” Baggar says. “It will give us the chance to test anti-parasitic drugs in a more relevant human system.”

Having a model with the apical side of cells facing outward is a key development that allows for better drug testing. Drug molecules come in all different sizes. In conventional three-dimensional organoids, the apical surface is enclosed within the organoid, making it difficult for both parasites and some experimental compounds scientists explore for their therapeutic potential to access the cells. Large molecules cannot pass through the basal side of the cell, hindering research on these molecules. By flipping the organoid so the apical surface faces outward, researchers can expose that surface directly to both the parasite and potential treatments. 

“That will help us identify targets for drugs and also understand how chronic infection happens and why, in immunocompromised individuals and children, this infection is fatal,” Baggar says.