As a young veterinarian in Zambia, Dr. William Witola wanted to know why the baby cows he saw were dying from a parasite resisting all treatment. Decades later, the University of Illinois veterinary medicine researcher is designing small molecules to silence that same parasite's gene expression, find potential drug targets and help end a disease afflicting children around the world, according to a university news release.

If successful, Witola's rapid technique would be the first of its kind to use these molecules to genetically manipulate the function of the Cryptosporidium parvum parasite, which can be deadly to humans and is notoriously difficult to study.

“I know what the problem is, as a veterinarian,” said Witola, a professor of pathobiology. “I know the problems the parasites inflict. As a scientist, I understand exactly what I need to do to address the problem.”

Using a recently awarded Grand Challenges Exploration grant from the Bill & Melinda Gates Foundation, Witola will further pursue his research approach into C. parvum, a parasitic protozoa affecting both animals and humans. The C. parvum parasite, according to a release from the Gates Foundation, is the second most common cause of potentially lethal diarrhea in young children in developing countries.

No known drug or vaccine exists for C. parvum, and it cannot be killed by the conventional treatment of drinking water, Witola said. Researchers have not been successful in maintaining a culture of C. parvum in the lab longer than five days, making it hard to manipulate.

Witola, however, has developed an innovative “gene knockdown” technique using small and stable molecules called Phosphorodiamidate mopholino oligomers (PPMOs) that can enter the parasite before it expires in the lab. These molecules penetrate the parasite's membrane, then attach to target genes' transcripts and inhibit the expression of the encoded proteins crucial to the survival of the parasite.

Witola hopes to develop a tool to study and validate gene function in C. parvum and a system that will assist in creating new, effective drugs to target the parasite's essential molecules.

“Drug companies only get interested when they see a clear path,” Witola said. “We'll have a system that shows, indeed, this gene is important for the survival of a parasite, and we'll move a step further and try and identify chemical lead compounds.”

The Grand Challenges Exploration grant provides funds for people around the world to explore ideas that have the potential to solve persistent global health and development challenges. Witola's project is one of more than 55 grants from Round 17 that the Gates Foundation announced for 2016, including one awarded to fellow Illinois researcher Patrick Degnan, a professor of microbiology. College of Veterinary Medicine professor Mark S. Kuhlenschmidt also received a Grand Challenges Explorations grant in 2013 for his work in developing a better system to maintain C. parvum cultures in the lab.

Witola said Kuhlenschmidt's work to extend the life of C. parvum cultures, as well as his protocols and advice, will be helpful as he tests his technique on parasite cultures in the lab. In addition, Witola said his Ph.D. students will be involved in maintaining the parasite culture, developing gene manipulation techniques and trying to analyze the effect of his technique on the parasite in the lab and in animals.

“I can actually go into the parasite and find out exactly what I can do to try to address that problem. I know that if I do that, then also I hope that would alleviate the suffering of so many people who have been neglected for such a long time,” Witola said. “That keeps me going.”