Although this issue brings a special focus to the field, engineering and the biosciences have hardly been strangers to the pages of Innovate over the past couple of years. And while we’re excited about the young new talent added to the College of Engineering’s ranks in this critical cluster area, all of our new researchers have a high standard to which they can aspire in the continuing work of these four senior members of our research faculty. Here, then, are some brief updates on projects previously featured in the magazine.
Julie Dickerson: ‘Meta!Blasting’ knowledge into young minds
A computer engineer, Julie Dickerson got into bioinformatics early this decade after taking a biology course for computer specialists, which put her on track to develop models of biological systems using a combination of relatively precise computation principles and the “fuzzy logic” she had studied as a graduate student. The fuzzy logic approach, she says, is better suited for dealing with the uncertainty in metabolic system modeling due to imprecise measurements and lack of knowledge within the field.
One product of her studies was an educational tool for high school students, in fact a video game called Meta!Blast that Dickerson developed with collaborator Eve Wurtele of the Department of Genetics, Development, and Cell Biology. Through interactive exploration, the goal of the game is to creatively engage students with some of the key biochemical processes in photosynthesis and other plant metabolic procedures in a compelling and active medium.
Dickerson and Wurtele recently received an educational grant from the National Institutes of Health (NIH) to evaluate the effectiveness of Meta!Blast as a teaching tool in several Iowa school systems. With the assistance of Ben Herman, currently a PhD student in education and a former high school science teacher, the team hopes to position Meta!Blast as an open-source teaching tool in schools across the country.
Beyond this, Dickerson is working with Robert Jernigan on proposals for the National Science Foundation’s Cyber-Enabled Discovery and Innovation Program to develop high-level 3-D microscopy models of how cell membranes change in real time. She is also collaborating with Jackie Shanks in Iowa State’s new Center for Biorenewable Chemicals (CBiRC) to model E. coli in order to optimize metabolic pathways for chemical production from plants.
Jackie Shanks: New twists in an ongoing project
When featured in the spring 2007 issue of Innovate, chemical engineer Jackie Shanks was working on optimizing the extraction of the alkaloids vincristine and vinblastine, two drugs used to fight leukemia and non-Hodgkin’s lymphoma, from the Madagascar periwinkle (C. roseus).
An ongoing project since 1999, Shanks has no plans to leave off this effort anytime soon, especially since her steady progress continues to attract funding and raise her profile in the plant engineering community. She recently chaired a conference session in Canada, bringing together several leading researchers working on C. roseus, and was an invited speaker at the Danforth Plant Science Center and the Phytochemical Society of North America.
A new area Shanks is looking at involves transcription factor engineering to manipulate the genes of plants to overproduce valuable alkaloids, such as those associated with C. roseus, as well as other chemical agents. It’s an approach to plant engineering Shanks admits viewing with some skepticism.
“There are negative effects you could have when you do that,” Shanks warns. “But our research team, including Professor Ka-Yiu San and Christie Peebles from Rice University, went ahead and overexpressed a transcription factor anyway.
“It’s interesting,” she continues. “Several genes do get induced that are important in the alkaloid pathway. But then the plant reacts by turning on new genes that turn these off. We knew it wouldn’t work, but it has identified other genes we normally wouldn’t think of that we could alter to allow the genes we want to stay ‘on.’ So we learn more about the pathway, and it gives us some new strategies. But it’s not a magic bullet.”
Shanks is also co-leader of CBiRC’s metabolic engineering group, where she coordinates research activities with the center’s other research arms. And though CBiRC’s emphasis is on industrial chemicals, she stresses that her work with the center isn’t wholly different from the study of central carbon metabolism in her other projects in plants and even microbes.
“It’s a different twist,” Shanks says, “but I’ve interacted with the people in my thrust before on different types of projects.”
Surya Mallapragada: A ‘step back’ moves cell study forward
By 2007, Surya Mallapragada and her collaborators had taken a “step back” from their continuing quest to repair and regenerate damaged nerve tissue across micropatterned polymer conduits in order to study and better understand the secrets of cell differentiation in the human body. By culturing adult stem cells in different media and over various substrates, their thinking went, they might better control the regeneration process by directing those stem cells to develop into mature cells that serve a specific purpose in the healing process.
Mallapragada calls the results of the past two years “pretty good.
“By using a combination of soluble factors from other cells,” she says, “we’ve shown that we can spatially control on one part of the substrate and have more neuron-like cells. On other parts of the substrate, where we don’t have the micropatterning, we have fewer neuron-like cells.”
Working with support from the National Institutes of Health, Mallapragada’s team is wrapping up the first phase of their in vitro studies and will move the project into animal studies later this year.
Future goals in this research line include development of a stem cell substitute for the commercially unavailable Schwann cells that constitute the myelin sheath for nerve cells in the peripheral nervous system, as well as adapting this process for applications in the central nervous system. Also, Mallapragada says, her work may be facilitated by the potentially greater availability of embryonic stem cell lines under the new Obama administration.
In addition, Mallapragada has undertaken a series of polymer-based studies with collaborators in the Department of Materials Science and Engineering, where she holds a courtesy appointment, and the University of Iowa Hospitals and Clinics in Iowa City. The studies, she says, focus on developing injectable substitutes to repair cartilage damage in order to prevent or minimize post-injury osteoarthritis.
Balaji Narasimhan: Integrating particle size and chemistry in vaccines
Searching for ways to boost the effectiveness of vaccines, Balaji Narasimhan has experimented alternately with both the chemical composition and size of the polymer adjuvants he uses to deliver antigens that trigger the body’s immune response, tailoring these to be released over an extended period of time—a technology especially valuable in parts of the world where follow-up booster shots aren’t always practical or even possible.
In the process of refining this technology, Narasimhan made a significant discovery: while some chemistries are internalized by immune cells rapidly, others are not internalized at all—yet these still trigger an immune response.
“Why does that happen?” Narasimhan asks. “Is the particle interacting with the cell at the surface level? Maybe ‘tickling’ the cell in a way that initiates a cascade of events that leads to an immune response? And how is that different from the particle that actually gets internalized by the cell?”
This line of inquiry has led Narasimhan to postulate a possible relationship between the size and the chemistry of the polymer adjuvant, a relationship he might be able to tweak in order to find what he calls the “sweet spots” that optimize the effectiveness of a given vaccine. In the meantime, Narasimhan’s vaccine group is currently conducting challenge studies, monitoring the effectiveness of their vaccines with mice infected with pneumonic plague, after which they will enter clinical trials with human subjects.
New projects include a $5 million grant from the U.S. Army to work with University of Nebraska Medical Center researchers to develop inter-nasal and epidermal patch vaccines against bird flu, as well as support from NIH to study the development of a single-dose anthrax vaccine. Finally, Narasimhan and his vaccine research colleagues across the Iowa State campus are exploring the possibility of creating a joint institute for the study of vaccine technologies with their counterparts at the University of Iowa.