Exterior cell surface design with glyco-engineering

Ali Chou • Posted: March 8, 2021

GlycoNet researcher Chantelle Capicciotti aims to understand fundamental biological questions by sculpting cell surfaces with defined glycans

Growing up in Beaverton, Ontario, as a first-generation student, she always thought she wanted to become a lawyer or a politician. In high school, something sparked her interest in science. With bits of self-exploration in different fields of science in university, and good mentors throughout her post-secondary education, Dr. Chantelle Capicciotti now leads her independent research group at Queen’s University. She is developing different chemical tools to help us understand the interactions between glycans—chains of carbohydrate molecules—and other biomolecules in our body.
Dr. Chantelle Capicciotti is sculpting cell surfaces with defined glycans, aiming to understand fundamental biological questions.

Specifically, Capicciotti is using a method called “glyco-engineering,” in which glycans are engineered or installed strategically onto different cell surfaces to probe their functions. We spoke with Capicciotti about her journey and her work.

How did you get interested in science?

I ask myself the same question. I don’t remember science careers being emphasized in the secondary school that I went to. Obviously, there were science courses or math courses, but the career prospects of pursuing sciences were not very clear to me. Being a first-generation student, I didn’t have any immediate family members who were in the realm of medicine or science. So, in general, it was pretty much me picking up bits along high school and university, and gradually finding out what options there were with science.

So, it was in high school that you discovered your fondness for science. What continued to fuel your interest in science afterwards?

When I applied to universities, I first enrolled in the neuroscience program at the University of Ottawa. While taking introductory courses, I was intrigued by organic chemistry, particularly how it could be used to build molecules and the molecules could be applied medicinally. I later transferred to the biopharmaceutical program specializing in medicinal chemistry. I enjoyed this program because it is a mix of subjects —chemistry, biochemistry, and biology. It also made me realize that I like chemistry, but I also like being able to apply the principles to make use of different molecules; I like biochemistry, but I’d like to understand the fundamental molecular interactions and use this knowledge to solve something else.

What happened next? How did you know that the academic route and research were what you wanted to do?

I was in a course taught by Dr. Rob Ben in the 3rd year of my undergraduate studies. I was impressed by his teaching style and was very persistent in working in his group for an undergraduate research project. However, at that time, I had no idea what I wanted to do beyond a Bachelor’s Degree. Rob’s lab had a positive research atmosphere. He was a great mentor in a way that he opened the conversation with me about graduate school, and at times, he would give me little nudges like ‘hey, I think graduate school is something that you’d be interested in!’ This encouragement sparked my interest in further pursuing a master’s degree, transferring to a PhD, continuing onto a post-doctoral fellowship, and then to academia.

Now as an Assistant Professor at Queen’s University, your research program is focused on glycoscience, a part of which is glyco-engineering. What is glyco-engineering?

Cell surfaces are covered with glycans, which are also called complex carbohydrates, and these glycans have specific functions. We want to understand the interactions between glycans and other biological molecules, not only what molecules bind to these sugars, but also what the binding means physiologically. Since glycans on the cell surface are hard to manipulate genetically, we are developing exogenous materials to remodel cells so that cells can display different patterns of glycans. We then examine how these different remodeled cell surfaces stimulate signalling sequences or other biological pathways when they interact with molecules in the body.

What is an example of the application of glyco-engineering?

One example is to identify how cancer develops and how cancer cells evade or “hide” from our immune system. We use a variety of enzymes and molecules to sculpt the surface of different cancer cell lines to see how changing the sugars on the cancer cells influence their interactions with the immune cells. More specifically, we ask the question: Can the immune cells recognize and kill the cancer cells if they have different types of sugars displayed on the cancer cell surface?

What excites you the most in your career now?

Seeing that my trainees wholeheartedly embrace this complex, challenging, and relatively new research area is exciting to me. At Queen’s University, many students are not exposed to glycobiology, and yet, my trainees are enthusiastically jumping into this field that they haven’t really learned about. It’s exciting to see them progress and develop scientific and critical thinking skills while pursuing very interesting projects.

It’s also exciting to be in the area of glycoscience with many avenues that haven’t been explored yet. The advancement of glycoscience is dependent on multidisciplinary approaches, and this is what I like—bringing together concepts in chemistry, biochemistry, and cell biology to answer fundamental questions in biology, health, and disease.

What is the impact of your research?

There are a few. One of them is that the tools we develop could enable other researchers to study complex glycan-protein interactions and the meaning of these interactions more easily. Another broader impact, in relevance to health outcomes, is that by looking at carbohydrate-protein interactions on cancer cells, we could develop new glycoprotein or carbohydrate targets for cancer therapeutics.

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