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Chemical engineer lands Research Starter Grant in Pharmaceutics

Josiah Smith works with a vial of chemicals as part of the research for Bret Ulery's Research Starter Grant.

Bret Ulery previously studied coupling peptides that cause known immune responses with fatty acids to make a drug delivery device that induces an even stronger immune response. The combination of both hydrophobic and hydrophilic components allows these materials to self-assemble in water into particles known as micelles — with hydrophilic regions on the outside and hydrophobic regions in the center. Photo by Hannah Sturtecky.

Getting that first competitive, external grant is a benchmark for faculty researchers, and Bret Ulery reached it when the Pharmaceutical Research and Manufacturers of America (PhRMA) Foundation selected him as a recipient of a Research Starter Grant in Pharmaceutics in December.

Ulery, an assistant professor in MU’s Chemical Engineering Department, received the one-year, $100,000 grant to continue his work on vaccine delivery systems. PhRMA requires a strong background in pharmaceutics — the study of the ways we can use new chemical entities or old drugs for new versions of safe and effective medication — for grant applicants.

Bret Ulery poses behind his student team - Josiah Smith, Rui Zhang and Logan Morton.

The funding will allow Bret Ulery (back row) and his student team — from left, Josiah Smith, Rui Zhang and Logan Morton — to engineer micelles whose efficacy will be assessed by cell and animal experiments, specifically using mice and rabbits. Photo by Hannah Sturtecky.

“Obviously, it’s huge,” he said. “I’ve been successful being on writing teams in the past and writing proposals with advisers for fellowships and things like that, but to get your first external grant, obviously it’s a huge win. It really puts weight behind what you’re doing and puts it out there that people recognize that you have good research ideas.”

The PhRMA grant will allow Ulery to expand the research he began as a postdoctoral researcher. He previously studied coupling peptides that cause known immune responses with fatty acids to make a drug delivery device that induces an even stronger immune response. The combination of both hydrophobic and hydrophilic components allows these materials to self-assemble in water into particles known as micelles — with hydrophilic regions on the outside and hydrophobic regions in the center. Ulery found that this setup allows for the entrapment of additional molecules to create even better immune responses than using just the peptide by itself.

“My work showed that when you make these nanoparticles, they’re comprised mostly of the vaccine with a little [fatty acid] tail on it, and they produce a pretty strong immune response, pretty similar to what we have as conventional formulations right now,” Ulery said.

In addition, Ulery also received a one-year, $48,357 grant from the MU Research Board. This grant will complement the PhRMA grant by funding research studying the vaccine potential of nanomaterials boosted by adjuvants, which are substances that enhance immune responses.

A microscopic photo of micelles.

Bret Ulery found that the creation of micelles – seen here – allows for the entrapment of additional molecules to create even better immune responses than using just the peptide by itself. Photo courtesy of Bret Ulery.

“What we want to look at is what happens when we either entrap molecules — commercially available ones — so we can create this combination system or even potentially replace that fat with adjuvants and templating out the structure with those to see what happens,” Ulery explained.

The funding will allow Ulery and his student team — graduate students Rui Zhang, and Josiah Smith and undergraduate student Logan Morton — to engineer micelles whose efficacy will be assessed by cell and animal experiments, specifically using mice and rabbits. With mice, Ulery said testing will focus on delivering vaccines under the skin and in the muscle, while testing with rabbits will focus on intramuscular delivery and an interesting area with limited research to date but significant promise — ocular delivery.

“You look at ocular vaccines, maybe vaccines [for the whole body] that can be put into an eye drop … which I think is a really exciting potential endpoint for this project for this grant,” Ulery said.

What Ulery enjoys most about this research, he said, was the variety of approaches a researcher can take throughout the course of investigation.

“I always think research engineers are half engineers, half scientists,” he said. “This proposal was geared toward designing new systems, but I like to think my engineer comes first — design the new system and if I see something interesting, really go down the rabbit hole of science and try to appreciate why this happens. Sometimes our ability to modulate and create new systems depends on our ability to know why this is even happening.”

Ulery thanked his student research team for their hard work, as well as Tom Phillips, MU professor of biological science, Jeff Adamovicz, director of the MU Laboratory for Infectious Disease Research, Fabio Gallazzi, MU research assistant professor of structural biology and Ali Salem, professor of pharmaceutics at the University of Iowa for their help with the research and obtaining the grant.