Scientist Profile - Jim Paulson

A Global Leader in Unraveling the Mysteries of Sugars and Their Impact on Disease

Scripps Research Professor Jim Paulson has spent about half his life studying sugars, or carbohydrates, that decorate the surface of cells to better understand their roles in cell communication and human disease … and his travails have brought him to the top of his field.

Jim has been named an industry pioneer and global leader in the field of glycomics by Technology Review, the Massachusetts Institute of Technology’s magazine of innovation.  The magazine considers glycomics to be one of the top ten technologies that will change the future.

Jim is the leader of the Consortium for Functional Glycomics, an international group of some 300 participating scientists who collaboratively study the complex dynamics of protein-carbohydrate interactions in the human body.  Like proteomics, the study of all the proteins produced by an organism, glycomics is important for unraveling the mysteries of the recently solved human genome because more than half of all proteins in the human body have sugar molecules attached.

In 2006, the consortium received a $40.7 million five-year “glue” grant from the National Institute of General Medical Science (NIGMS) – the second NIGMS grant the consortium has received.  The first, awarded in 2001, was a five-year grant of $34 million.

“The most recent award was especially gratifying in that it was a vote of confidence that the program is doing well,” said Jim.  “I take great pride in the consortium because it benefits so many researchers.”

The consortium was formed to support multi-disciplinary, multi-institutional research projects that would be considered beyond the means of any one group.  It is shared by Scripps Research, the University of California, Massachusetts Institute of Technology, Palo Alto Research Center, Emory University, Indiana University, and colleges, universities, institutes, and medical centers in the United Kingdom, Japan, Russia, The Netherlands, and elsewhere – the consortium represents more than 25 countries.

“It was the NIGMS idea to ‘glue’ together the work of independently funded investigators and to provide the funds necessary to accelerate research into this critically important field,” said Jim.  “We know that sugars aid in the proper trafficking of cells in the body, and that they can modulate signaling from the outside of a cell to the inside, but what we know so far is just the tip of the iceberg.  This grant will help us uncover what lies beneath.  While the field is still in its infancy, there has been a major upsurge – in fact, if you look at the major journals, they all typically now contain articles and reviews on glycomics.”

The most popular resource established by the consortium at Scripps Research thus far 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 CFG 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.

NIGMS director Jeremy M. Berg said, “Since it was formed, the consortium has done an exceptional job by developing and disseminating resources in the study of sugars to the wider scientific community.”

Berg continued, “The technology developed by the Consortium for Functional Glycomics allows researchers to assay hundreds of carbohydrate varieties in a single experiment and is the kind of technology that the consortium specializes in.  The glycan microarray offers a detailed picture of viral receptor specificity that can be used to map the evolution of new human pathogenic strains, such as the H5N1 avian influenza, and could prove invaluable in the early identification of emerging viruses that could cause new epidemics.”

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 been with Scripps Research since 1999.  For years he worked for Cytel, a San Diego biotech company as a senior executive and researcher, in the field of developing drugs.  “It has been exciting to work in this field from the perspective of both the academic and private sectors.”

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!