by Ann Y. Robinson
Joshua Selsby, professor of animal science at Iowa State University, studies the mechanisms of muscle disease and injury. Last year, he was recognized with the Mid-Career Achievement in Research Award from the College of Agriculture and Life Sciences, based on an impressive record that includes more than 70 publications.
One of his primary research interests is the progressive, fatal disorder Duchenne muscular dystrophy. The most common muscular dystrophy in children, DMD is caused by a deficiency of an important cellular building block, the protein dystrophin. Without dystrophin, muscles are not able to function or repair themselves properly. They weaken over time until the whole body is affected. DMD mostly affects boys – about one out of every 5,000 boys is born with the disease.
One research avenue Selsby is exploring is the possibility that the disease and its progression is influenced by obesity or insulin resistance, a metabolic dysfunction associated with diabetes. Both are common in DMD patients.
“It’s unclear if this is related to a fundamental aspect of the disease process or results from weight gain linked to patients’ decreased activity. Or the relationship between obesity and the disease could be due in part to standard therapeutic treatments, such as prednisone, often associated with weight gain,” Selsby said.
While attending a conference, he had an “aha moment” thinking about the potential connection between obesity and DMD, and a related research problem.
“The most frequent research model to study Duchenne muscular dystrophy is a mouse model, called the mdx mouse, which is extraordinarily lean. If it’s possible that obesity-related factors significantly affect the disease or its progression, we would be very unlikely to see this by studying it in such a different metabolic context,” he said.
Funding successes and challenges
Thanks to support from the Muscular Dystrophy Association (MDA), Selsby and collaborators, Rudy Valentine, associate professor of kinesiology, and Justin Walley, associate professor of genetics, development and cell biology, have a new project to test hypotheses about the disease’s links to obesity. Their experiments will also improve understanding of how to effectively study DMD.
“I’m thrilled with the investment that MDA has made with us,” Selsby said. “But getting to this point has been a big challenge.”
Along the way, he submitted four grant applications to the National Institutes of Health (NIH) for the project, the first in 2019. The initial proposal scored well but wasn’t funded, Selsby said.
“They said we needed to demonstrate that mdx mice could become insulin resistant or diabetic. That had never been established - people thought it was impossible, but we went for it,” he said. “We did a preliminary study, and we discovered that indeed, you can feed them a diet that makes them insulin resistant. With that new preliminary data, we refined and resubmitted our proposal. Frustratingly, the scores got worse.”
At the same time, they had submitted a parallel proposal to the MDA right before COVID hit, and in the spring of 2020, MDA decided to cancel that round of grants.
“We had a little bit of money that we were able to use to keep the project limping along, which gave us a basis on which to submit our next proposals,” he said.
Two more submissions on the project to NIH were unsuccessful. However, they did receive another Duchenne-related grant from the NIH for a different topic, the regulation of a protein called PKR, which Valentine is leading.
Eventually, the MDA reopened its grants process, and the team once again submitted their proposal to study the DMD-obesity linkages. This time, they were successful. The project was funded for three years and started in 2022.
As Selsby reflected recently on the grants process roller coaster, he said there have been times when sustaining his research has been difficult. “Small pots of internal funding have been incredibly important to help us survive lean times. But those opportunities are also limited and usually very competitive.”
“To sustain a research focus on DMD, we’ve had to persevere through many setbacks,” Selsby said. “One thing that has kept us going is the fact that this is the most frequently occurring fatal disease linked to the X chromosome. It reaches across all races and cultures. A desire to alleviate this immense heartache and suffering is very motivating.”
Resources for researchers
Iowa State University offers a number of resources for faculty looking for assistance with funding and grant applications.
The Office of the Vice President for Research is an important source of expertise and support for research and scholarship. The OVPR regularly sponsors competitive opportunities including a small seed grants program and matching grants for equipment.
CALS also offers limited research-related grants to fund travel, conference-hosting and equipment purchases, for example. A list of CALS Internal Funding Opportunities can be found on the CALS Research website. Some support comes from funds that originate in USDA programs, with eligibility requirements that include involvement in an approved and up-to-date Experiment Station Hatch project. Support can also be sought through private partnerships, industry and alumni. The CALS Research Excellence Support (CARES) Team helps faculty explore grant possibilities and manage applications.
CALS Endowed Dean’s Chair Daniel J. Robison encourages researchers to persist through the ups-and-downs of funding challenges.
“We are so proud of our exemplary faculty,” he said. “As one of the premier agriculture and life sciences research institutions in the country, we are always trying to improve our capacity to support important work like Joshua Selsby’s. His perseverance and willingness to go after a variety of funding sources, to stay on track, to respond innovatively and effectively to reviewer feedback on proposals, and more – all show outstanding efforts on the part of Dr. Selsby and the teams he works with! And this work on DMD is of the highest order.”
This is the first in a series of articles highlighting CALS researchers and their journeys to funding and enlightenment. To every success, there’s a back story.