Systems Biology Used To Study Cellular Glycomics in White Blood Cells

Two recent papers have presented the results of attempts to use a systems biology approach to understand the cellular glycome. The glycome represents a cell's total sugar or carbohydrate composition. It has been described as exceeding the complexity of the proteome because of the even greater diversity of the glycome's constituent carbohydrates, and is further complicated by the sheer multiplicity of possibilities in the combination and interaction of the carbohydrates with each other and with proteins.

Systems biology is a mathematical and experimental approach that focuses on whole systems of complex biological functions and interactions instead of studying individual units, such as a single gene or protein, in isolation. Investigators at the University at Buffalo (NY, USA) used this approach to examine the relationship between gene expression, glycosyltransferase activity, glycan expression, and selectin-binding function in different cell systems, including human neutrophils, undifferentiated HL-60 (human promyelocytic cells), differentiated HL-60, and HL-60 synchronized in specific growth phases. Selectins are a large family of membrane proteins that bind oligosaccharides on other cells tightly and specifically, and are involved in signal transduction across the plasma membrane.

Their results were published in two papers. The first article, which appeared in the August 26, 2008, online edition of The FASEB Journal, described the experimental techniques used to measure enzyme reaction rates involved in glycosylation, and then drew critical correlations with gene expression, enzyme kinetics, and the structures of glycans. The second paper, which was published in the October 7, 2008, online edition of the journal Bioinformatics, described a computer model that utilized the data produced by those experiments to establish a basis for predicting the structures of glycans on cell surfaces.

"Our goal is to find ways to alter carbohydrate structures or glycans on the surfaces of white blood cells,” explained senior author Dr. Sriram Neelamegham, professor of chemical and biological engineering at the University of Buffalo. "Systems biology is well suited to this research because it helps us develop the mathematical concepts to enable us to influence and enhance our understanding of how the glycome functions. This then produces clues on how we might manipulate the adhesivity of white blood cells to the blood vessel wall.”

"The data produced experimentally allows us to determine key steps in the glycome reaction network that controls the final glycan structure that appears on cells,” said Dr. Neelamegham. "This approach then provides an in silico tool that can be applied to perturb the system of interest, such as the glycosylation network.”

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State University of New York, University at Buffalo