NUI GALWAY:THE ROLE that sugar plays in our lives is more critical than most people imagine. In fact, every living cell is coated with glycans or sugars and these sugars are involved in the interactions between cells and a whole range of physiological processes ranging from fertilisation and stem-cell differentiation to tumour metastasis, immune regulation, inflammation, and host-pathogen interactions. They are centrally involved in communication between cells.
“I am still learning and I am still fascinated by the cellular alphabet,” says Lokesh Joshi, principal investigator with the Science Foundation Ireland funded Alimentary Glycoscience Research Cluster (AGRC) at NUI Galway. “We are still trying to decode the language of cells and how they speak to each other. We need to develop the technologies and tools to listen better to how the cells speak to each other.”
Gaining a deeper understanding of this communication could help in the development of new technologies for the rapid diagnosis of diseases such as cancer, the creation of new, more highly targeted and effective drugs, and the development of new generations of nutraceutical health drinks.
“We are working with Teagasc and a number of Irish SMEs to explore how we can find value in the sugary components of milk and other foods,” says Joshi. “Every bacteria that causes disease uses sugar to bind itself to cells in the body.” If they use other sugars to bind onto the cells, it can help prevent the disease.
This is a process known as competitive inhibition which, rather like some weedkillers, prevents disease by almost literally crowding it out. “Our main goal is to look at how bugs in the gut use sugars to find the right home,” Joshi adds. “And the new technologies we are developing for this can be used in other areas of research as well.”
Drug development is among the main areas of this research. Many drugs are made of proteins which are present in the human body in any case – they are simply manufactured outside of it to be administered in suitable doses to fight particular diseases. However, like other cells, these proteins are covered in sugar but because they have been manufactured outside the human body it may not be the right sugar. The wrong sugar will trigger the body’s immune system and it will be rejected.
“This causes side effects and will reduce the efficacy of the drug,” says Joshi. “There are two things we can do to help. The first is to take the drug and say whether it has the right sugar or the wrong one. The second is to help them put the right sugar on it.”
If the right sugar is used the body’s immune system will not be activated and the medicine will be allowed to work unimpeded with no unpleasant side effects.
Cancer is another very important area of the research. “Cancer cells coat themselves in different types of sugar depending on the stage of the cancer,” Joshi says. “They do this to communicate with or hide from the body. For example, during the angiogenesis stage they coat themselves in a sugar which attracts blood cells and the growth of blood vessels. During metastasis they shield themselves from the body’s immune system by cloaking themselves in a sugar which renders them invisible. A lot of pathogenic bacteria use this trick of stealing sugars and disguising themselves with them.”
What the AGRC research is aimed at is the development of a sugar coating for anti-cancer and other drugs which only bind with the particular sugars on the target cells. This would make chemotherapy far less debilitating for the patient and far more effective.
“What we are making is gloves for hands,” he says. “The hands are the sugar coatings on the cells we are looking to attack and the gloves will be attached to the therapeutics. The drug will only attach itself to those hands. This opens up a huge field of infectious diseases to us.
“Every virus or microbe uses sugar to bind it to a host – this includes microbes involved in conditions such as MRSA – and our goal is to come up with novel sugars to assist in their treatment.”
Another application of the AGRC’s research is the actual diagnosis of diseases. “We have been selected by the EU for grant funding for research into the next generation of glycobiomimic and glycosensor tools for the diagnosis of cancer glycobiomarkers.
“Take the example of blood cancer. How do you tell which cell is a normal blood cell and which is a cancer cell? One way of telling is that the sugar marker is different. We can look at the sugar coating and tell which one is which.”
This naturally has important applications for the early diagnosis of such diseases. “One thing that we are very keen on is developing rapid diagnostic tests for a range of diseases,” he says. “My goal is a future where people can go to see their GP and give a small blood sample which can be quickly analysed for various diseases including cancer. The blood would be analysed for the different sugar markers and early and quick diagnosis of a range of conditions will be facilitated without the need for invasive biopsies and so on.”
And he believes this is only the beginning of the journey. “I am super-excited about what we are doing here,” he says. “All the indications are that developing the tools to decode the cellular alphabet will lead us to the development of therapies and diagnostic tools in a whole range of areas.
“This is a very new field but we are making a lot of progress and we are working closely with the pharmaceutical and medical equipment companies as well as the food industry on a lot of very interesting research collaborations.”
