Biotechnology, generally defined as the practical application of advances made in biology, is a more than $35 billion enterprise in the United States alone. The field encompasses all facets of the life sciences, from molecular to environmental, and from agriculture to human physiology. Biotech advances hold promise to cure major diseases such as Alzheimer’s, diabetes, arthritis, multiple sclerosis, AIDS, heart disease, and cancer. It is also one of the most research-intensive industries in the world, with the industry as a whole spending more than half of its revenues on research and development over the last five years.
Rensselaer is staking its claim in the burgeoning field, making a top-flight biotech research program a key goal in The Rensselaer Plan, established five years ago. The plan identifies four focal areas that build on existing strengths at the Institute: biocatalysis and metabolic engineering, functional tissue engineering and regenerative medicine, integrated systems biology, and computational biology and bioinformatics. Research in these areas translates into the development of new drugs for major diseases, tissue repair and replacement, and biosensors and monitoring for security and biohazard detection.
Highlighting both the new facility and faculty recruitment, Palazzo describes how the Institute is quickly making its mark in becoming a “premier biotechnology hub.”
“We’re establishing the infrastructure and achieving critical mass in talent and leadership,” he says.
Building a Premier Biotech Program
Rather than forming new departments around the focal areas, Rensselaer has created groupings called “constellations” for the four research focal areas. Each constellation comprises a multidisciplinary mix of senior and junior faculty, post-doctoral associates, graduate students, and even undergraduates. Robert Linhardt, the Ann and John H. Broadbent Jr. ’59 Senior Constellation Professor in Biocatalysis and Metabolic Engineering, who came to Rensselaer last year from the University of Iowa, likens the constellation concept to observing groupings of stars in the night sky. “When you look at those stars as a whole, you see some image or shape in the night sky,” he says. “It takes shape only by virtue of a grouping.”
Rensselaer spotted Linhardt as one of those “stars.” His work encompasses both basic research as well as therapeutic application. He was a co-discoverer, with Robert Langer of MIT, of polyanhydrides as drug carriers. This led to the successful clinical application of polyanhydride-based drug delivery agents for the treatment of advanced brain cancer.
Today, Linhardt, an organic chemist by training, has been at the forefront of a “carbohydrate renaissance” and is internationally known for his work with bioactive carbohydrates. “Everyone knows what carbohydrates are,” he says. “They have a bad name from the Atkins diet. In reality, however, carbohydrates are essential to life.”
To illustrate biocatalysis and metabolic engineering, Linhardt offers the example of tissue plasminogen activator (TPA), a protein with carbohydrates linked to it. While TPA occurs naturally in humans, it also can be administered as a therapeutic drug to interrupt a heart attack in progress. The effectiveness of TPA depends on the molecular structure of its carbohydrates. Linhardt’s group is working to understand the relationship between structure and function as well as the enzymatic pathways that can link (or cleave) carbohydrates to (or from) TPA. That’s biocatalysis, the catalytic alteration of biologically important molecules.
Metabolic engineering researchers are tinkering with those pathways. Cell culture is used to make TPA, but Linhardt says mammalian cells are expensive, hard to grow, and can be contaminated with viruses.
“We’re using insect cells to make the same product. It’s an alternative that has the potential to be more efficient and economical. In order to do this, you have to engineer the pathway in the cell to make the right product,” says Linhardt, who sees himself “sitting in the middle” of the continuum between biology and engineering.
George Plopper, assistant professor of biology, also bridges the disciplines, with joint appointments in biology and biomedical engineering. At the same time, he collaborates with other faculty from mathematics, biomedical engineering, and chemistry.
Plopper’s research focuses on functional tissue engineering. He works with stem cells extracted from banked bone marrow samples and then grown in a biology lab.
“What we’re trying to do is take adult human stem cells and get them to differentiate into bone-forming cells,” he says. “The idea is that if we can make this work in a culture dish, then we’d know how to replicate it in the body. So we can implant a person’s stem cells back into one’s body at the site of injury to heal the body much more quickly.”
The research ultimately will have therapeutic applications. He employs substances the body uses to build bone called extracellular matrix proteins. “We don’t actually build bones in the dish,” he says. He wants cells to show the potential to do so once they are placed back into the body.
Kristin Bennett, associate professor of mathematical sciences, works with Plopper to model stem cell differentiation, expressing the outcome measures as functions of experimental conditions. “There are more combinations than anybody in their right mind would ever, ever do,” Plopper says. Bennett’s work will help predict those conditions under which the stem cells will convert into bone-building cells.
Fern Finger, assistant professor of biology, is working to understand the role of septin family proteins in organ development. Her research explores how septins help form cell-cell junctions in the heart, which may be important for heart pumping and for maintaining heart structure during aging. Her research is supported by a $198,000 grant from the American Heart Association.
Other researchers are combining biology and engineering at the molecular level. Jan Stegemann, assistant professor of biomedical engineering, uses collagen combined with carbon nanotubes to engineer tissues. Specifically, Stegemann works with heart tissue, which is electrically conductive. The potential application would be to patch diseased hearts.
Stegemann recently has received a number of grants for his vascular tissue engineering research, including a $200,000 grant from the New York State Office of Science, Technology and Academic Research (see "Supporting the Heart"). He has also received a two-year, $373,000 grant from the National Institutes of Health and a four-year, $260,000 grant from the American Heart Association.
“One of the problems when people have heart attacks is that it basically kills part of the heart wall. That part then can’t contract like the rest of the heart wall, and therefore you get impaired pumping of blood,” Stegemann says. “The dead part also won’t conduct electrical signals from the other parts of the heart, and so it interferes with the pattern of signaling. The hope is that conductive nanocomposite materials could help bridge the electrical signaling.”
Stegemann also collaborates with Plopper in bone engineering. Their team has developed a technology in which they can encapsulate cells in a three-dimensional “bead” of extracellular matrix only slightly larger than the cell itself. Using what he’s learned from experiments in laboratory dishes, Plopper adds stem cells and bone-building factors to the beads.
“These beads have a consistency like toothpaste,” Plopper says. “If a paste can be made with the capability to form bone, broken bones could be glued back together with living tissue.”
Like Plopper, Stegemann weaves biology and engineering in his research.
“If you were to characterize my work, what I’m really interested in is how cells interact with their environment,” Stegemann says. “But because I’m an engineer, I want to use that knowledge to my advantage to make new tissues. Part of it is understanding the biology and disease processes. Part of it is getting the cells to do what you what them to do.”
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