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Human Glycome Project Forges Ahead With Support From New England Biolabs, Genos, Waters

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NEW YORK – New England Biolabs, Waters, and Genos have agreed to support the Human Glycome Project, with pro bono reagents and services worth €3 million ($3.4 million) over the next three years.

The new partnership will support the analysis of glycans in 30,000 human samples by the end of 2021, according to Gordan Lauc, the co-director of the Human Glycome Project and a professor of biochemistry and molecular biology at the University of Zagreb in Croatia.

"The idea is to enable researchers from outside glycoscience to add glycomics to their studies," Lauc said. "Waters and NEB are providing consumables, while Genos will use these consumables to perform glycan analysis," he said.

Lauc helped to initiate the Human Glycome Project last October. Richard Cummings, director of the National Center for Functional Glycomics at Harvard University, is the other co-director of the project. The global effort is modeled on the Human Genome Project and aims to map the structures and functions of human glycoconjugates, or glycans, oligosaccharides covalently attached to the backbone of proteins.

By gaining better knowledge of glycan structure and impact on function, it's possible to understand the function of individual proteins or complex multiprotein and multicellular systems, organizers maintain. Alterations in glycan activity have been linked to a variety of diseases.

"The human glycome is exceedingly complex and the knowledge about glycans is lagging significantly behind the knowledge about genes and proteins," noted Lauc. "There is a need to coordinate activities of researchers in the field to ensure optimal use of available resources."

Lauc also said the project serves as a vehicle to standardize analytical methods, chemical standards, and databases, so that results obtained in different laboratories can be compared.

The project's objectives include: mapping glycan structures in a protein and site-specific manner, recording inter- and intra-individual variability of all glycoproteins in all human cells and tissues; determining the impact of individual glycans on the function of their glycoconjugates; understanding the mechanisms, pathways, and systems that regulate glycosylation; describing the normal human glycome in a body fluid- and tissue-specific manner; developing protocols, reagents, analytical tools, and reporting guidelines to promote best research practices; creating a public database of human glycome data; and promoting education in the field of glycoscience.

The project held its inaugural meeting in Dubrovnik, Croatia, last year, and a second meeting in Split, also in Croatia, last month, where NEB, Waters, and Genos officially joined as associate members. Since the project commenced, Lauc said participants had worked on "securing centrally available resources that can be made available to participating researchers."

Lauc is also the CEO of Genos, a Zagreb-based biotechnology company that employs around 50 full-time personnel. As much of its work is supported by research grants, Lauc said that Genos largely functions as a "research institute," but it offers glycosylation analysis services as well using ultra performance liquid chromatography (UPLC) and liquid chromatography–mass spectrometry (LC-MS). As an associate member, Genos will offer analytical services to the initiative for free.

Chris Taron, scientific director of protein modification research at Ipswich, Massachusetts-based NEB, said the company has maintained a research group focused on glycobiology since 1990, and called the firm's support for the Human Glycome Project a "natural progression of its interest" in this area of science. The company offers a variety of reagents for glycan analysis. It also provides a N-glycan sequencing kit that can be used to characterize typical N-linked glycan structures.

NEB will provide PNGase, an enzyme that cleaves N-glycans from glycoproteins, as part of its contribution to the project.

Taron said that the Human Glycome Project should advance researchers' understanding of glycobiology and enable the development of targeted therapies.

"NEB believes that such a systematic exploration of the human glycome has the potential to help write a new chapter in translational medicine," he said.

Milford, Massachusetts-based Waters, for its part, will provide access to its Acquity UPLC technology and GlycoWorks RapiFluor-MS sample preparation kits as part of its contribution to the project.

According to Lauc, the vendors have agreed to contribute reagents and services to analyze 10,000 human samples per year. The samples will be analyzed by project participants, selected through the initiative's steering committee. The results of all analyses will be made available to all members of the community via depositories that are being developed in collaboration with the Swiss Institute of Bioinformatics in Lausanne, Switzerland. 

Lauc noted that the Human Glycome Project does not currently have dedicated funding. Rather, participating investigators are feeding findings from their own related endeavors into the project. The website for the effort provides a list of individually funded studies that are supporting the aims of the Human Glycome Project.

There are currently five divisions of the project. Harvard's Cummings leads a division focused on human glycome diversity, while Lauc is overseeing inter-individual variability of the glycome of human body fluids. Daniel Kolarich at the Institute of Glycomics at Griffith University in Australia is leading a division devoted to inter-individual variability of the human tissue glycome while Michael Pierce of the University of Georgia's Complex Carbohydrate Research Center is overseeing work done on functional relevance and regulation of the human glycome. Manfred Wuhrer, head of the Center for Proteomics and Metabolomics at Leiden University Medical Center in the Netherland is responsible for the fifth division dedicated to analytical methods and standards for glycoscience.

"All work is being funded by individual research projects of participating investigators," commented Lauc. "We hope this will change with time and that we will be able to provide central funding for the project."

Without a major source of funding, the Human Glycome Project is setting up short-term targets and organizing subgroups to advance the goals of the project. One such goal, Lauc noted, is to analyze, separate, and make available as standards all major glycans in human body. Another is to map inter-individual differences in total plasma glycomes and IgG glycomes and their association with major complex human diseases, he said.

Harvard's Cummings said that members of the project are involved in sequencing the human lung glycome and human brain glycome at the moment. His center is also making synthetic glycopeptides and glycans as standards, and is creating archives of human materials, tissues, cells, and glycoproteins for worldwide distribution for analysis. The center is also making antibodies to glycans that can be used to identify the spatial and temporal expression of glycans using histochemical specimens, such as pathologists would collect, he said.

Cummings acknowledged that the glycome is "much more complex than the genome" and that it might take "billions of dollars and decades of work" to map it. "It is expected that human glycan diversity is immense, and several hundred thousand different glycans probably exist," said Cummings. "To identify and sequence them, and characterize their expression in health and disease is a formidable task."

At the same time, he said the payoff from the Human Glycome Project may be significant, as defects in glycan synthesis and turnover are associated with many diseases and disorders. It will also complement genomics research.

"Understanding the glycome will also give us tremendous insights into the enigmas of the genome," Cummings noted. "There are hundreds of different genes that produce glycans and degrade them, and thousands of genes encoding proteins that become glycoproteins," he said. Cummings added that while the project is "daunting," participants are dedicated to developing strategies and sharing resources including synthetic and natural research materials and data.

"We have a huge task ahead," said Cummings, "but we're fearless."

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