Research at Rensselaer

Prof Lindhart sequences polysaccharide

Institute research group compares carbohydrate biopolymer, amino acid

Research by Professor Robert Linhardt, constellation chair and professor of the chemistry and chemical biology department, involves sequencing the first carbohydrate biopolymer. This is an alternative name for a polysaccharide, a long chain of individual sugars such as glucose and other variations on a saccharide naturally synthesized in nature.

He compares carbohydrate polymers to amino acid biopolymers, more commonly known as protein. According to Linhardt, the distinction made is that, “their structure is complex but not as complex as carbohydrate biopolymers. Moreover, it is well known that proteins have sequence and there are convenient methods available to chemists, biochemists and biologists to determine protein sequence.”

The debate, then, is whether carbohydrate biopolymers have a single structure or sequence, and, if so, what that sequence is.

Original studies are being done on the carbohydrate biopolymer drug bikunin, commonly used in Japan to treat acute pancreatitis. Linhardt reveals that his colleague, Professor Toshi Toida of Chiba University, is a world-renowned expert on this drug. In addition, his colleagues at the University of Georgia, Professor Jon Amster and Dr. Franklin Leach, have access to one of the most powerful mass spectrometers with which to study biopolymer structures. “Our group at Rensselaer, consisting of myself, Dr. Mellisa Ly—the lead author and a graduate student who recently completed her Ph.D. at Rensselaer—and Dr. Tania Laremore, are experts on carbohydrate biopolymers.”

He currently has a large team of researchers working with him on this sequencing project. This team consists of approximately 15 postdoctoral fellows who hold Ph.D.s, 15 graduate students who are studying for their Ph.D.s, and 22 undergraduate students working in the lab. The research group is split into two project teams containing a mixture of students of all academic levels with a variety of fields as their primary background.

Linhardt’s research group is housed entirely on the fourth floor of RPI’s Center for Biotechnology and Interdisciplinary Studies, though his resources spread far beyond the city lines of Troy, New York. The sequencing project, in particular, works in collaboration with a group of analytical chemists at the University of Georgia and a pharmaceutical chemist at Chiba University in Japan.

The carbohydrate biopolymer sequencing project is funded by a grant from the National Institutes of Health. This grant pays for salaries, supplies and equipment, and provides overhead funds to the Institute.

The sequencing study showed—for the first time—that carbohydrate biopolymers can have a defined sequence. Specific to this project, there has been an enhancement in knowledge of the structure of bikunin using freshly developed technology that will also be applied to better understanding of other, more complicated carbohydrate biopolymers.

Linhardt mentioned that the results also “challenge biologists to explain how the cell controls the biosynthesis of carbohydrate biopolymers having sequence.”

Linhardt concludes, “Like all research, we have answered a few questions and have generated many more new questions. This work serves to move the frontiers of knowledge and to train a new generation of scientists.”