Today, Sullivan, an assistant professor of chemical engineering at the University of Delaware and Merck Faculty Fellow, is applying her knowledge and talents to an area critical to human health--she's building new materials for delivering healing drugs and gene therapies to diseased and damaged cells in the human body.
Sullivan is UD's latest recipient of the National Science Foundation's prestigious Faculty Early Career Development Award. The highly competitive award is bestowed on those scientists and engineers deemed most likely to become the academic leaders of the 21st century.
The five-year, $489,798 grant will support Sullivan's research to determine how cells interact with potential drug carriers and how the resulting structural changes of the carrier affect its ability to efficiently deliver its payload.
“It's an honor. I was thrilled to hear the news,” Sullivan said. “The National Science Foundation has always been a respected funding organization. Colleagues in my field do the reviews for the proposals, so that is very gratifying.”
“The College of Engineering has some of the best young engineering faculty in the country, and Prof. Sullivan is a perfect example,” Michael Chajes, dean of engineering, said. "Her work in the area of new materials for delivering drugs and gene therapies to human cells is groundbreaking research. This award will enable her to take important steps towards moving the research closer to implementation. I look forward to watching Millie's career continue to blossom,” Chajes noted.
Sullivan wants to harness the cell's biological environment to “productively evolve” new drug or gene packaging materials as they make the rough-and-tumble journey from a blood vessel, through the connective tissue, through the cell membrane, and finally into the nucleus or other organelle within a target cell where the package will open up to deliver its contents.
“It's a challenge to achieve because in protecting the DNA or drug, you generally make it less accessible to its target,” Sullivan said. “We need to design packaging materials that protect their cargo, but that also promote the release and functionality of the payload once it reaches its target site,” she noted. “What elements within the cell would allow this unpackaging? That is what we want to find out.”
Currently, Sullivan is working to design synthetic DNA delivery materials that mimic elements of the architecture and function of histones in chromosomal DNA packaging. Histones are positively charged protein complexes that function as “spools” around which chromosomal DNA is wrapped. They display a series of peptide “tails” with specific sequences that act like switches, and can activate or suppress the transcription process by which DNA is unraveled and read.
Sullivan is creating gold nanoparticles functionalized with histone tail sequences strongly associated with transcriptional activity. When used for packaging therapeutic DNA, these materials will protect and direct their payloads during extra- and intracellular transport. Once they are exposed to the specific chemical cues within the cell's nucleus, the materials are pre-programmed to “trigger,” resulting in the partial release and activation of the cargo DNA.
Confocal fluorescence microscopy and cryo-transmission electron microscopy will be used to investigate what happens to the materials once they are introduced to cells, and to determine if they do, indeed, “loosen up” and affect DNA transcription, Sullivan said.
The educational component to the research project is designed to expose students to engineering before they reach college.
As part of the UD College of Engineering's Research Experiences for Teachers program, Sullivan is ready to pilot teacher internships aimed at developing course modules in bioengineering for the high-school curriculum.
Two high-school teachers--including one science teacher and one math teacher--and an in-service teacher in mathematics education will spend six weeks doing research in Sullivan's lab this summer. Their work will include both an experimental component and a modeling component to give each teacher a lead role in his or her area of expertise.
Additionally, teaching assistantships will be offered to high-school students who will work alongside the teachers in the lab and do the full experiments. The students will be co-mentored by UD undergraduate and graduate students.
“Bioengineering and biomaterials research have the potential to lead to dramatic improvements in human health,” Sullivan said. “I'm excited about doing the science, and about bringing engineering into the high school classroom.”
Sullivan received her bachelor's degree from Princeton University and her doctorate from Carnegie Mellon University, both in chemical engineering. She conducted postdoctoral research in tissue engineering and matrix biology in the Hope Heart Program at the Benaroya Research Institute in Seattle.
Article by Tracey Bryant
Photo by Kevin Quinlan