The surface of our cells are covered in sugar molecules called glycans. The field of glycomics leverages their enormous diversity to develop better and more precise diagnostics.
More commonly known as sugars or carbohydrates, glycans are involved in a range of crucial biological roles, including maintaining tissue elasticity, tackling pathogens, and modulating the immune system. Since they play a role in most biological functions, and many more get uncovered, researchers are increasingly looking at the glycome – the complete set of all glycans in a cell – to develop diagnostics.
The human genome comprises about 25,000 protein-encoding genes. In comparison, the human glycome comprises millions of different kinds of possible glycans. Glycans are composed of simple sugars linked together to form all kinds of complex structures. Glycan structures change according to environmental stimuli such as pH, hormonal stimulation, and inflammation. The glycome of a cell thus provides a detailed picture of what’s happening at the molecular level within the cell. Leveraging this enormous diversity of glycans enables the development of highly-specific diagnostics that offer very detailed information.
Glycans in inflammation and immunity
Glycans can be attached to other molecules, such as proteins and lipids, in a process known as glycosylation. The glycosylation patterns seen in our cells have been long known to play a crucial role in maintaining the health of the immune system and keeping inflammatory responses in check. Detecting changes in glycosylation patterns, thus, provides valuable insights into the development of a range of diseases.
“Since protein glycosylation is a dynamic process constantly occurring in the body, it can reflect its current status and can be used to monitor disease progression as well as personalize treatments,” says Nina Skorytchenko, CEO of Avenna. This UK-based startup develops glycomic tests for inflammatory bowel disease (IBD), chronic inflammation, and vulnerability to life-threatening levels of inflammation from Covid-19 infections.
Avenna’s biomarker assay for IBD measures glycomic data to predict which patients need more intensive therapy. “It can be used with other omics data in a decision tree for treatment management,” Skorytchenko said. “This has the potential to reduce remission and reduce the incidence of flares, reduce patient consultations, investigations, and hospitalizations, improve the quality of life, possibly delay the accumulation of intestinal damage, and personalize IBD treatment management.”
Antibodies are one example of proteins that have glycans attached to them. Looking at the glycosylation patterns of antibodies reveals much more insights into disease progression than just looking at antibody levels. For instance, while the levels of a type of antibody known as immunoglobin G are indicative of general immunity, its glycans betray specifics of the inflammation that the antibody is fighting.
“Immunoglobulin G is principally responsible for the recognition, neutralization, and elimination of pathogens and toxic antigens. Glycans attached to this molecule give it an additional dimension of complexity and therefore regulate its function. This provides valuable information about the current health status of the individual – body inflammatory status in particular,” Skorytchenko added.
Glycans as cancer biomarkers
Changes in the glycans produced by a cell are one of the hallmarks of cancer. Many clinically approved cancer biomarkers, such as the carcinoembryonic antigen (CEA) for colon cancer, are glycoproteins. This is why startups and researchers are adding glycomic approaches to the repertoire of tools for cancer detection. However, conventional diagnostics generally focus on the protein part of the glycoproteins, which may provide poor specificity for cancer diagnosis.
“For instance, if someone has elevated CEA levels in their blood, they might be a heavy smoker, or might be suffering from cancer. And in the latter case, it might be colorectal cancer, ovarian, pancreatic, or breast cancer — we don´t know, because the marker is not tissue-specific,” said Tomas Bertok, co-founder and CEO of Glycanostics.
Slovakian biotech Glycanostics leverages the diversity of glycans to develop non-invasive, early cancer diagnostics. By measuring the changes in the glycan content of specific antigens in blood, the company’s diagnostic kits can detect breast and prostate cancer.
“Glycans yield a huge combinatorial potential to encode biological information. Thus adding these analyses to commonly used tests may significantly increase the accuracy of current diagnostics. The greatest value lies in a combination of different marker types in a diagnostic algorithm – we are using glycans, proteins, and some other clinical and biological data as well.”
Detecting pathogens with glycans
When bacterial pathogens attack our cells, immune cells are able to detect glycans on their cell surface in order to identify and destroy them. However, to evade the immune system, bacteria often produce glycans that mimic those on the host cells. Analyzing glycans on bacterial cell surfaces opens up diagnostic as well as therapeutic applications.
British biomedical startup FluroretiQ combines nanomaterials and optical sensing technologies to quantify glycans on pathogenic bacteria. In particular, the company can identify common bacteria implicated in urinary tract infections within 15 minutes.
“Glycans play an essential role in cell-to-cell recognition processes for infection, and it is through the recognition of glycan patterns that bacteria can recognize, adhere and colonize the host tissue for infection. This mechanism is key to our technology,” James Preece, Product Manager at FluoretiQ, explained.
Compared to protein-based diagnostics, glycans offer commercial advantages too. “They are significantly cheaper to manufacture, can be readily modified, and have greater stability at room temperature than their protein-based counterparts,” Preece added.
Going beyond diagnostics, new insights into the glycome are furthering the development of therapies that use synthetic glycans to control immune responses and inflammation. Just like previously with genomics and proteomics, the success of the emerging field of glycomics will rely on our ability to quantify glycans and glycopeptides cheaply and fast.
“Complex glycans were omitted in biomedical research simply because we didn’t have the technology necessary for their analysis. Now we do, but it is time-consuming and extremely expensive. We managed to do these glycan analyses on a laboratory table in a few hours,” Bertok told me. It is this shift to fast and affordable desktop equipment that will define what’s next for the field.