Unraveling the Mysteries of Sugars
Professor Jim Paulson
Scripps Research Professor Jim Paulson is widely considered to be an industry pioneer and global leader in the field of glycomics, with merits coming from MIT's Technology Review, and as the leader of the Consortium for Functional Glycomics, an international group of some 300 participating scientists.
Glycomics, or the study of the complex dynamics of protein-carbohydrate interactions in the human body, has wide-reaching potential.
A useful resource established by the Consortium for Functional Glycomics at Scripps Research has been the glycan array (glycans are relatively complex carbohydrates, sometimes called polysaccharides). It offers scientists an enormously powerful cutting-edge research tool that makes it easier and faster to determine how a diversity of glycan binding proteins interact with sugars in biological systems. From humble beginnings, there are now more than 450 structures in the array, and it has been used by over 200 investigators to investigate the biology of sugars and their roles in disease processes.
Some viruses, like influenza, use sugars on the outside of human cells to gain entry into human cells. The array has been used by dozens of investigators, including recent research from Jim's lab and the lab of fellow Scripps Research scientist Ian A. Wilson, to investigate the host specificity of avian influenza virus. It was used to identify mutations that could enable adaptation of a particularly virulent form of H5N1 - the avian flu virus - to spread in the human population. A custom array is used by the Center for Disease Control to survey the avian and human influenza viruses isolated worldwide.
"With continued outbreaks of H5N1 virus in poultry and wild birds, further human causes are likely," said Wilson. "The potential for the emergence of a human-adapted H5 virus, either by re-assortment or mutation, is a clear threat to public health worldwide."
Data from the array is posted on a public web site, The Functional Glycomics Gateway, in a partnership between the consortium and Nature Publishing Group. It provides a comprehensive resource for functional glycomics research where the information generated by the consortium is rapidly disseminated to participants and the public alike, benefiting the scientific community as a whole. It highlights new and important contributions to the field, providing a one-stop overview of the latest research in glycobiology, and generates 120,000 visits per month.
Now that the resources have been built, the consortium's focus is on using those resources to uncover new biology, according to Jim. "Ultimately, the public will be the prime beneficiary of this research as new discoveries are translated into treatments for disease."
Jim's own research laboratory is pursuing an approach to active targeting of sugar binding proteins on B cells for therapy of B cell leukemia and lymphoma. By targeting a single cell type, therapies can be developed with less side effects than therapies where other cells are also affected, such as through chemotherapy. Jim is one of a handful of scientists internationally attempting this approach.
"I'm enthusiastic about our results thus far," said Jim. "It's looking very good. By knowing what sugar binding proteins are found on specific cells, we can design synthetic sugars that will target and carry a therapeutic payload to a single type of cells."
Jim has always had an interest in discovery. In grade school in the Midwest, he would examine protozoan life from pond water under a microscope; in high school, he was doing basement experiments on fruit flies; in college, at MacMurray College in Illinois, he had the dream to do an experiment that no one had ever done before, and by the time he reached graduate school at the University of Illinois, he was indeed doing things that no one had done before... and still is every day!