Scientists will use genome sequencing and algae to understand primary ciliary dyskinesia.
A young girl from an Amish community came to St. Louis Children’s Hospital to see Thomas Ferkol, M.D., for what her family thought were allergies. But it was quickly apparent that she had something more complicated than allergies. She had primary ciliary dyskinesia, and many of her relatives might as well.
Through his work as a pediatric pulmonologist at St. Louis Children’s Hospital, Ferkol, associate professor of pediatrics, cares for children with primary ciliary dyskinesia, a disease that occurs in one in 15,000 to 20,000 births. In these patients, the cilia, the tiny hair-like structures that move fluids, mucus and inhaled particles out of the lungs, ears and nasal passages, don’t move correctly, causing persistent wheezing, coughing and chronic infections of the respiratory tract and middle ear. In addition, half of the patients with this disease have reversed internal organs, called situs inversus totalis. Men are usually infertile.
Ferkol and his colleagues have found a high incidence of primary ciliary dyskinesia in children from Old Order Amish communities and have identified two genetic mutations in this population, but he strongly suspects that there is at least a third. With funding from the Children’s Discovery Institute, Ferkol will work with Susan Dutcher, Ph.D., interim director of the Department of Genetics, and Seth Crosby of the Washington University Genome Sequencing Center, to find the genetic mutations that lead to the disease in children in this community.
Ferkol said he hopes to find the mystery gene and its mutation with the resources available in the Genome Sequencing Center.
“The technologies and high-throughput capabilities they have are astonishing and provide a powerful tool to understand human disease,” he said.
In addition, Ferkol and Dutcher are looking at a simple, single-celled organism that may lead physicians to greater insights and new treatments for patients with the rare disease.
They have hatched a rather creative approach to modeling the disease in algae called Chlamydomonas, which rely on whipping, tail-like structures termed flagella to move. The researchers plan to introduce the genetic mutations known to cause primary ciliary dyskinesia into the algae, then determine whether specific drugs or small molecules would improve the function of these flagella. Once the researchers identify potential treatments on the algae, they will then test their findings in cells from patients with primary ciliary dyskinesia to determine whether the treatments would improve cilia function.
“While using the Chlamydomonas model may be high risk, the approach could have a high reward,” Ferkol said. “If it proves to be successful, it could revolutionize our approach toward drug testing in this disease,” Ferkol said.
Ferkol credits the Children’s Discovery Institute for promoting interdisciplinary collaboration to find the basis of disease.
“One of the advantages of the Children’s Discovery Institute is that it allows investigators to test novel ideas,” Ferkol said. “It provides a mechanism by which clinicians and scientists can collaborate to understand pediatric disease.”
Article written by Beth Miller