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.
If successful, Dr. 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 notoriously difficult to study.
“I know what the problem is, as a veterinarian,” said Dr. 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.”
Recently awarded with a Grand Challenges Exploration grant from the Bill and Melinda Gates Foundation for his approach, Dr. Witola will be able to further pursue his research 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.
I hope [my work will] alleviate the suffering of so many people who have been neglected for such a long time. That keeps me going.
Dr. William Witola
No known drug or vaccine exists for C. parvum and it cannot be killed by the conventional treatment of drinking water, Dr. 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.
Dr. 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.
Dr. 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,” Dr. 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 funds people around the world to explore ideas that have the potential to solve persistent global health and development challenges. Dr. Witola’s project is one of more than 55 Grand Challenges Explorations Round 17 grants announced for 2016 by the Gates Foundation, 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.
The infrastructure of the College of Veterinary Medicine — both in support from fellow faculty members and the college’s large animal facilities — makes it an ideal place to continue his research into the parasite, Dr. 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, Dr. Witola said. In addition, Dr. 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,” Dr. Witola said. “That keeps me going.”
The Grand Challenges Explorations grant is a $100 million initiative funding more than 1,228 projects in more than 65 countries since its launch in 2008. Open to anyone from any discipline and organization, the initiative awards initial grants of $100,000 twice a year, and successful projects have the opportunity to receive an additional follow-on grant of up to $1 million. New applications will be accepted in February 2017.
Photo by L. Brian Stauffer