AUSTIN, Texas—Krishnendu Roy, assistant professor of biomedical engineering at The University of Texas at Austin, has received $1.6 million through two National Institutes of Health grants to improve the body’s ability to attack foreign invaders.
One grant will focus on producing immune-stimulating cells from mouse stem cells. The other will involve engineering novel vaccines to incite native versions of these cells to fight diseases.
Dr. Krishnendu Roy in front of a magnified image of polymer microparticles that will be used to deliver a DNA-based vaccine. In the two-year, $405,000 vaccine grant, Roy’s laboratory will develop DNA-based vaccines to deliver immune-stimulating factors (foreign genes) to naturally-occurring functional dendritic cells of the human body.
Photo: Patrick Cummings
The four-year, $1.2 million grant on mouse stem cells will provide the biomedical community with a better understanding of the best engineering parameters for turning mouse stem cells into cells that can be trained to mount an immune response against cancerous cells, bacteria or other invading organisms in mice.
This research using mouse stem cells as starting material (progenitors) would eventually augment studies by other researchers developing the human equivalent of these immune-system cells, called functional dendritic cells.
“We hope to generate readily available disease-fighting cells from these progenitor mouse cells, which our preliminary work suggests is feasible,” said Roy from the College of Engineering.
The research should also help drive decisions on how best to prompt stem cells to develop into other types of cells that constitute the body’s protective immune system.
Roy’s laboratory in the Department of Biomedical Engineering will expose mouse stem cells to synthetic, 3-D structures that mimic the interior of porous bones or other body sites where they would normally develop. As an added developmental prompter, the researchers will enclose the cells and 3-D scaffolding, and flow nutrients through the containers to mimic conditions inside the body.
A process called microarray analysis will catalog the genes that are active within the progenitor cells and in the functional dendritic cells that ultimately develop inside the containers. The dendritic cells’ gene expression can then be compared to that of similar cells that normally develop inside mice.
Roy and Professor Philip Tucker from the College of Natural Sciences will also study how well the scaffold-developed dendritic cells prompt an immune response in animal models and in immune-system cells in flasks. Tucker holds the Marie Betzner Morrow Centennial Chair in Natural Sciences’ Section of Molecular Genetics, Microbiology and Immunology.
In the two-year, $405,000 vaccine grant, Roy’s laboratory will develop novel materials for DNA-based vaccines that can be used to deliver immune-stimulating factors to naturally occurring functional dendritic cells in the human body.
The stimulatory DNA will be foreign genes, which will be carried within circular genetic elements called plasmids. Plasmid DNA does not incorporate into human genes, and thus won’t cause unwanted side effects.
Roy’s laboratory will coat the plasmids onto the surface of synthetic, biodegradable microparticles. To enhance the immune response to these coated polymer microparticles, the researchers will entrap naturally occurring chemicals that stimulate a stronger immune response (chemokines) inside the microparticles.
The plasmid-coated, chemokine-containing microparticles will be tested in animal models for their ability to serve as a vaccine against bacteria or other invading organisms.
For more information contact: Becky Rische, College of Engineering, 512-471-7272.