Breaking down barriers in osteoarthritis

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Known for its excellence in research, McGill University is home to a host of professors and scientists whose work contribute to scientific innovation. In tribute to the amazing research conducted within McGill’s walls, each month Science & Technology will feature student researchers who have helped contribute to the cutting edge science conducted at the laboratories. This series hopes to shine a spotlight onto the hard work of undergraduate students who dedicate themselves to research in the lab. 

For many students, the first day of work entails filling out papers and easing into the new job. But on Joseph Yang’s first day, he was handed a scalpel and was asked to collect cartilage from mice.

“I really wasn’t expecting to do so many things my first day,” he said. “It was kind of nasty at first—having to cut everything out—but eventually I got pretty good at it. [It got to a point] where I had to dissect around 15 to 20 mice a day.”

Yang, currently a U1 microbiology and immunology student, recently received a second place award for his poster in the Medical Sciences category at the Undergraduate Research Conference on Oct. 10. Submissions were mostly from fourth year students, so Yang was surprised when he heard his name announced. His poster focused on the research he had conducted this past summer at the laboratory of Vice Chair of research at the University of Toronto and adjunct scientist in developmental & stem cell biology Benjamin Alman. Yang’s research was conducted under the supervision of Peter Kannu, a staff physician in the Clinical and Metabolic Genetic Department. The lab is located in Toronto at SickKids Hospital.

“The goal of my research was to see whether my protein, called aquaporin 9 [which regulates transport of both solute and water] was implicated in causing osteoarthritis [a degenerative joint disease],” Yang said. “We used a mouse model and knocked out aquaporin 9 to see the differences in gene levels of osteoarthritis markers like COLX.”

By knocking down the protein, Yang was able to observe what happened in mouse cells when this protein was no longer functioning. He paid particular attention to certain genes known for their involvement in osteoarthritis.

“What happens in osteoarthritis is that there are cells called chondrocytes in the joint area that are supposed to be in the resting state, but they start differentiating into a state known as a hypertrophic state,” Yang said. He explained that in the hypertrophic state, the cells change their morphology and produce collagenX, instead of collagen2 which is required for the proper structure of healthy cartilage. This state leads to a breakdown of cartilage, resulting in the pain associated with osteoarthritis.

Yang’s project consisted of classifying whether or not the protein aquaporin 9 was involved in osteoarthritis. His results from this summer indicate that this protein does indeed have implications in the disease.

“We noticed that when we knock out aquaporin 9, [making the protein non-functional] the expression level of certain genes responsible for breaking down cartilage are overexpressed. Essentially, when we knock out aquaporin 9, these gene levels go up.” In other words, when aquaporin 9 is not functional, genes implicated in osteoarthritis make more gene products than they normally do in healthy individuals.

Yang also looked at the difference in expression of the osteoarthritis marker COLX between wild type cells—those with the functional aquaporin 9 protein—and knock-out cells—those without aquaporin 9. A ‘marker gene’ in this case is a gene that is known for its expression in a certain disease.

“We stained for COLX expression and one thing that was really interesting was that […] the COLX expression levels were only different in the articular cartilage of the joint [flexible connective tissue],” Yang explained.

This observation was very important to his project, as it helped localize where arthritis affects the joint. It also indicated a strong correlation between aquaporin 9 and osteoarthritis—the goal of Yang’s project.

As for many undergraduate students, this summer position was Yang’s first experience in research. One of the benefits of this experience was that it enriched his taste for research and enhanced his learning in the classroom.

“[Now] when I am learning about PCR and DNA sequencing, I have physically done it before. It’s not an abstract thing, because I have already done it. [My lab work allows me to] appreciate the basics of why we are learning about this technique.”

Having enjoyed his experience, Yang is currently working in a lab in the Institut de Recherches Cliniques de Montréal (IRCM) under the supervision of Director of Biochemistry of Epigenetic Inheritance Research Unit and associate IRCM research professor Nicole Francis, whose lab focuses on proteins involved in cell division of mitosis. In the future, Yang hopes to apply to a MD-PhD program.

“I like research, but I think I would like to do [a] MD-PhD. I want to do more research to make sure that I really do like it. [It] can be frustrating.”

Yang emphasizes that, as an undergraduate student, getting involved in research can be a difficult process. However, he notes that perseverance is essential to acquiring the opportunity to become a part of a lab community.

“[When I applied], I had just finished first year, so I had no lab experience,” said Yang. “My understanding of these biological techniques was pretty limited, so I knew I was in a [less advantageous] position to apply for these full-time positions over the summer.”

“I applied to a lot of labs—25 or something like that—and if I was lucky I would get a response from five. Three said they only took fourth or third year students, but luckily I got an interview at one lab, and that was the lab I actually worked at. I think it is important to keep trying— even if you might not get a response, don’t be upset by that. Apply to a lot of labs and really show that you want to do it.”

Yang said he admires the level of intellectual discussion and collaboration that occurs within both labs he has worked at so far, and he looks forward to the opportunity to continue acquiring a taste for research in his future years at McGill.

 

Favourite lab technique:

“[Collecting cartilage from mice] takes a while because you have to be careful not to dissect other stuff [besides] the cartilage. It was tedious at first, but it is a really good technique [to learn]. You have to focus a lot. Also, [although it was not my favourite task] stacking pipette tips was [surprisingly] fun—[the summer students] raced each other!”

Most embarrassing moment:

“I had a lot of embarrassing moments. For example, we were doing this project where we had to culture cells for 21 days and check them every three days. We had to compare the first three days with the 21st day. I contaminated the cells [on the 21st day] so it basically failed.”

If you were a mad scientist, what would you do in your lab?

“I would make a time machine and go back [in time]. I have a few people I want to meet.”

Advice for other students applying to a lab:

“Apply early, because spots fill up. The applications [for my lab] were due at the end of January but I applied in early December. When I went home for the Winter break, I did my interview at the lab. A lot of positions are filled by people who have connections at the lab, so there are a really small number of spots available. If you don’t apply early they will fill up so fast.”

Joseph Yang is a U1 microbiology and immunology student