Dr. Meaghan Jones Talks Epigenetics, Allergies, and the Immune System
Dr. Meaghan Jones recently completed a postdoctoral fellowship in the laboratory of Dr. Michael Kobor at the Centre for Molecular Medicine and Therapeutics at BC Children’s Hospital where she explored the role of epigenetics in the development of the immune system. Dr. Jones sat down with us to discuss her research, a resulting patent, and the journey from postdoctoral fellow to professor.
What has been your research interest during your postdoc?
My graduate work was in developmental epigenetics, looking at how the epigenome influences cell fate through the activation and repression of genes. But I was always interested in the environmental component to epigenetics as well. This brought me to the Kobor lab, where we study how the environment alters the epigenome in a developmental context. During development, we know that cells are growing, changing, and making decisions about their fate. This means that the epigenome is already in flux, so when an environmental change is experienced during these sensitive periods of development, it could influence developmental fate. The question is: can we find out what kinds of environments make these epigenetic changes, and are they linked to long term health outcomes in children?
Why are you interested in the epigenetic landscape of the immune system specifically?
Being in the Kobor lab presented me with a great opportunity to work with the AllerGen (Allergy, Genes, and Environmental) Network, which allowed me to work with immunologists, allergists, and other professionals who have fundamental knowledge of blood and the immune system. Blood is also one of the easiest tissues from which to acquire and measure the epigenome. So focusing on the immune system was partly general interest, and partly self-interest.
Having said that, the immune system is fascinating! We know that innate immune cells are pretty much functional at birth, but adaptive immune cells aren’t. They need postnatal exposures in order to learn their environment. That’s one of the reasons why getting maternal antibodies through breastfeeding is so important. I’m interested in the epigenetic changes that are acquired in both parts of the immune system through in utero and postnatal exposures, and whether one or more of these is likely to influence health outcomes.
What have you found so far?
The epigenome of innate immune cells seems to be similar between umbilical cord and adult blood, which makes sense because these cells are already functional at birth. But the epigenome of adaptive immune cells changes a lot as they experience postnatal exposure. Even if you look across people (everyone has had different exposures throughout life), there are still a lot of changes that are commonly found between cord and adult blood. There are some kind of consistent developmental changes happening. A preprint of this work can be found here.
Most of your work has been focused on DNA methylation. Have you looked at any other epigenetic modifications?
Unfortunately other epigenetic modifications are much more difficult to analyze in samples from human populations. Most of the work that I do now is with human cohort studies, which is why we have a lot of cord blood. We’re not always involved with the specific cohort and the sample collection, which means that we don’t always get whole cells and access to chromatin. Oftentimes it’s just DNA. Fortunately, because we know that the epigenome functions as a whole, DNA methylation is still a great indicator of what’s going on.
A couple of years ago, your research led you to file a patent. How did that come about?
It’s an interesting story! At the time, we were working with cord blood DNA methylation profiles from a cohort of around 190 children in Cape Town, South Africa. I started doing some of the basic quality control tests on the samples, and they looked weird. Based on the methylomes, about 30 of the male samples looked more like female samples. You can usually separate the two really easily, because X inactivation in females results in very different DNA methylomes than in males.
The first thing I googled was whether Klinefelter syndrome was really common in South Africa, which it isn’t. But I couldn’t think of another reason for why so many of these boys had these strange profiles. It was actually a really amazing PhD student in the lab, Lisa, who pointed out that the profiles looked like what would happen if you mixed blood from a boy and blood from a girl. So we went and looked at the collection procedures, and it turns out that there was a pretty high likelihood, given the way this blood was collected, that they had maternal blood contamination in the cord blood sample.
Unfortunately, this meant that we couldn’t use the contaminated samples. But we didn’t know how many of the samples had also been contaminated with maternal blood. So we had to come up with a way to screen for maternal contamination. Since all we had at the time was DNA methylation data, we looked for CpG sites in the genome that could differentiate between cord and adult blood. We eventually identified a set of three CpG sites that could be pyrosequenced to accurately identify whether maternal contamination is present.
We started to think about this as a potential commercialization opportunity, because it seemed like it would be of interest to cord blood banks. We contacted the UBC University-Industry Liaison Office, and we showed them the paper. After a lot of paperwork they filed a provisional patent for us, which was quite exciting. Then they started to market the idea to cord blood banks. Unfortunately, we decided to let the patent lapse this year because it didn’t get any interest. Most of the banks said that contamination wasn’t something that happened often enough for them to warrant additional screening.
You were recently hired as an Assistant Professor at the University of Manitoba. What advice would you give to other postdocs still on the search?
It’s tough. I was on the job market for two years before I found my job. I know it sounds a little cliche, but networking is really important. I ended up finding out about this job before it was posted because of people that I’d previously met. Additionally, it’s important to have mentors who are not directly responsible for your career. So not your supervisor or your committee members, but other people who are helpful and can be there to support you. Plus it’s important to remember that as hard as you work (and you can work really hard!), you have to get a little lucky as well. So just start applying!
Thank you for taking the time to discuss your research with us, Meaghan! We wish you the best of luck in your new position!