The Rationale Behind Scientific and Commercial Interest in Glycomics

For decades the international scientific research community was engrossed in the Human Genome Project (HGP) whose primary goal was to determine the sequence of chemical base pairs which make up DNA and to identify the physical and functional nature of the approximately 25,000 genes of the human genome. HGP was a 13-year project coordinated by the U.S. Department of Energy and the National Institutes of Health and was completed in 2003. A key aspect of HGP was the federal government's commitment to transferring technology to the private sector, which in turn fostered the growth of the biotechnology industry and resulting new medical applications. HGP spawned the new scientific field known as genomics, the study of gene structure.

Basic research questions arise from the enhanced knowledge of the genetic code, such as: what are the roles of different genes and in what cellular processes do they participate; how are genes regulated; how do genes and gene products interact; how do gene expression levels differ in various cell types and states; and how is gene expression changed by various diseases or treatments. The advances in genomics have had a cascading effect as scientists can delve deeper into the structure and interactions among the biochemical bases of living matter and as a result new areas of study have emerged.

The progression of areas of study mirror the processes involved and can be diagrammed as follows:

Genomics -> Transcriptomics -> Proteomics -> Glycomics

• Genomics is the study of the genome, the entire DNA sequence of an organism. While every cell of an organism contains the same complete genetic information, only selected cells respond to each of the approximately 25,000 available genes.
• Transcriptomics is the study of the transcriptome of an organism. The transcriptome is a subset of the genome, less than 5 percent, which is transcribed into mRNA molecules. This transcription process is the first step in gene regulation and studying transcription promotes the understanding of gene regulatory networks. Analysis of the transcriptome of an organism yields information about where genes are turned off or on in the body, elucidating the possible relationship between a gene and disease processes.
• The result of the transcription process is the production of protein and the proteome represents the complete set of proteins produced by an organism in all of its component cells. Proteomics, the study of the structure and function of proteins, is a complex endeavor as proteins vary over time in response to changes in the environment of a cell.
• The field of glycobiology studies the structure and function of complex sugars called glycans. Glycobiology influences proteomics, as many proteins are post-translationally modified by glycosylation, the addition of carbohydrate groups (glycans) to a protein to form a glycoprotein, which in turn increases the functional diversity of proteins. The glycome defines these posttranslational modifications which encode a vast amount of information at a minimum genetic cost. Glycomics then is the study of the complete set of glycan structures expressed by specific cells, tissues or organisms.

It is easy to recognize that the complexity of study in each field increases from genomics to glycomics. In fact, it is expected that the potential chemical information content rises exponentially from genomics to glycomics. Considering that there are approximately 25,000 human genes, the amount of information to be derived by glycomics is staggering. The study of functional glycomics is rapidly emerging as a mechanism to thrust carbohydrates into the mainstream of biology and biomedicine.

Why the Interest in Glycomics?

Researchers have determined that minor differences in glycan structures can play a major role in biological functions. In fact, glycans are involved in all life phases beginning with embryonic development. For example, consider oligosaccharides (also called simple sugars), a class of saccharides that contain a small number of component sugars. Oligosaccharides play a critical role in many biological processes including biorecognition, interactions between cells, immune response, infection and inflammation.

The emerging field of glycomics may eventually result in new drugs; new uses for existing drugs; and/or existing drugs may be modified to become more efficacious. Current methods of manufacturing protein-based drugs do not necessarily modify the artificially created proteins with the same sugars found in the human body. This discrepancy causes the liver to quickly flush the protein-based drugs from of the body. However, utilizing the appropriate sugars that are compatible with the human body could result in more efficient treatments and reduce the required dosage of protein-based medication.

Sugar chemistry is also involved in the progression of cancer, helping to transmit the signals that trigger unchecked cell growth. Glycomics may eventually play a critical role in the fight against cancer. Researchers are also investigating the role of sugars in the development of Parkinson's, Alzheimer's and infectious diseases like AIDS and herpes. Sugars may also influence stem cell biology, organ transplantation and tissue engineering.

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