Carbohydrates are critical to our understanding of human diseases, says Professor Nicolle Packer.
"We're finding that these sugars are not just important in our diet, but more importantly, they completely coat the cells and are therefore involved in just about every disease in humans, such as cancer, cystic fibrosis, infertility, influenza and microbial infection.”
Packer was part of the team that originally set up the Australian Proteome Analysis Facility at Macquarie, a not-for-profit research institution that offers a range of highly technical screening of proteins.
Some of the research technology includes mass spectrometry, high pressure liquid chromatography (HPLC), protein sequencing, amino acid analysis, protein separation and protein quantitation that is largely used for biomarker discovery.
Now research in the fields of proteomics, combined with glycobiology, is uncovering the key role played by the carbohydrates attached to the proteins. These are active in almost every biological function, Packer says.
“Sugars are also hugely implicated in our immune response,” she says.
Her research looks at glycomics, which has become the name used to refer to all biologically active sugars, including those carbohydrates attached to proteins.
While there’s now a lot of research under way into how our genes code for proteins, there’s still much investigation to be done into the activity and functions of the carbohydrates that are added onto about half the proteins made in the body.
“Carbohydrates are a bit trickier to look at than proteins, they require different methods, different expertise and different software, so here at Macquarie we are developing new tools for the analysis of these molecules,” says Packer.
Glycomics defined
Our cells carry complex sugars or carbohydrates which are also called glycans, and they are made up of individual sugar molecules linked to one another in lots of different ways.
“Glycomics is not about the sugar you put in your cup of tea, or the glucose levels we measure in our blood that are linked to diabetes,” she says.
The molecules that she is interested in are attached in various shapes and sizes to the proteins in our body. While they can originate from the sugar we eat, our bodies change and add them to other complex molecules to perform various functions at a cellular level.
Packer's team is one of the first research groups to link glycomics to the proteomics and genomics revolution in biological research.
Data from all over the world is coming together in her team's projects, at both the analytical and software development levels, offering new insights into what sugars attach to the surface of cells and how they interact to bring about diseases.
By combining innovative technologies and the informatics needed to analyse data, the projects make it possible to develop new drug targets and diagnostics for these diseases.
Glycomics and cancer
One example is the use of glycomics screening to recognise cancer cells, so we can reduce the extent of surgery or find new markers of cancer metastasis.
“In a cancer cell, the sugars coating the cell’s surface change and are then not recognised by the surrounding cells, allowing them to migrate – or metastasize,” Packer says.
“Cells which may have been sitting in the liver or the heart and which change their surface sugars as a result of the cancer, can then bypass the mechanisms of the body that keep like cells together.”
For example, her team has developed a method which uses mass spectrometry to identify, on the surface of the cell, the exact boundary of tissue affected by ovarian cancer.
“Surgeons need to get the boundary of a cancer to cut it out, and at the moment, we rely on people inspecting a series of pathology slides through a microscope to work out which part of the tissue is cancerous,” she says.
Generally, surgeons will cut a larger boundary to allow for human error and ensure they have captured all the tumour cells.
“Because this method is so exact and relies on a chemical profile of the presence of particular sugars rather than visual inspection of tissues, we're hoping it will develop into a very accurate pathology test, potentially reducing the impact of cancer surgery.”
Glycomics and immunity
Packer says that nearly all of the microbes and viruses that infect humans will bind to human cells by attaching to specific cell surface glycans.
“When bacteria invade our body, they start the infection process by landing on the surface of the cell and fastening onto particular sugars that coat the cell,” she says.
As part of the body’s immune response, the sugars in tears, sweat and saliva attract bacteria – and then the body washes the invaders out, through normal processes.
“That gives us some interesting insights into the protective mechanism tied up in all of our body’s fluids; we are exposed to the environment all the time but we don’t get infected all the time because of this immune response.”
This mechanism has led to the development of some important drugs such as anti-flu virus drugs Relenza and Tamiflu and other pharmaceuticals which are made up of chemicals that stop the pathogens binding to our cells.
Developments in glycomics are already having a substantial impact upon future research toward both diagnosing and preventing infectious disease, Packer says.
"I truly believe these molecules are important in the way our bodies function and how and why they stop functioning," she says.
“As one of my researchers said to me: 'It's all about sugars. It always was and always will be'."
