High-throughput technologies that enable scientists to handle a large number of repetitive tasks rapidly and with a high degree of precision have contributed to advances in many areas of biomedical research. Glycomics, the study of glycan structures in a cell or organism, has not benefited in quite the same way, as the analysis of these highly diverse sugar-based biomolecules is notoriously complex.
The HighGlycan project has risen to the challenge. With two more years to go before the project ends in October 2016, it has already developed methods that make it possible to measure the glycans in clinical specimens — blood samples, for instance — in high-throughput mode and made the technology available to the wider biomedical research community. The partners have also begun to commercialise various types of sample preparation kits based on their insights.
Sugars under scrutiny
HighGlycan focuses on glycosylation, the process by which sugars are attached to other molecules such as proteins to form a wide variety of glycan structures with very different roles. “Mammalian cells are covered with a thick layer of glycans, which are involved in the interaction with the neighbouring cell, the communication between cells and so on,” says project coordinator Dr Manfred Wuhrer of Leiden University Medical Centre. “In virtually all biological processes, you have glycans and glycosylation changes going on.”
Glycosylation thus reflects many aspects of health and disease. Various forms of cancer, for example, have been shown to correspond to specific glycomic changes. Comparing these structures in samples volunteered by patients and healthy individuals could therefore help to spot differences that are reliable indicators of specific diseases, providing leads for the development of new diagnostic tools.
However, says Wuhrer, this kind of approach can only produce useful results if the samples are taken from a large group of persons — and processing such a large batch of samples requires high-throughput technologies. So far, this has not been possible for glycosylation analysis. “The lack of clinically used glycosylation biomarkers is mainly due to technological limitations,” he explains, “and the HighGlycan project addresses this bottleneck.”
In addition to its potential in clinical settings, glycosylation analysis is useful for the makers of medical drug products. “Glycans are also of increasing importance with respect to the development of biopharmaceuticals,” Wuhrer notes, “so the biotech industry also needs glycoanalytical technologies that allow the processing of many samples.” They can, for example, help to check how cell cultures in an incubator are developing.
HighGlycan shortlisted promising technologies that are already in use, found a way to apply them for glycosylation analysis and issued guidance on how to prepare the samples. Batches of several hundred or thousand samples can be processed in this way, says Wuhrer, adding that this guidance has been published and is freely available to the wider research community. The partners are also developing a range of test kits supporting this type of analysis, some of which are already being used by clients in the pharmaceutical industry.
In addition, the partners are using their approach to validate and identify biomarkers for a number of diseases. Wuhrer mentions promising leads for the detection of maturity-onset diabetes of the young (MODY), a type of diabetes that is often misdiagnosed as the far more common types 1 and 2. Correct diagnosis supported by HighGlycan technology, he explains, will allow clinicians to ensure that MODY patients receive the right treatment for this particular form of the disease.