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14 Flourish

I spoke with the lovely Morgan Coburn for this month’s episode of Her Royal Science. Though we recorded this episode in September, we decided to hold off release until this month in commemoration of Diabetes Awareness Month. In this episode, we touch upon Morgan’s exciting work, investigating the role of microglia in Alzheimer’s disease. We also talk about Type 1 Diabetes, how she was diagnosed, and how her STEM story is intimately intertwined with her diabetes story.

Though discussed post-episode recording, Morgan importantly mentioned that more efforts need to be made to include disability in the discussions of improving diversity and inclusion in STEM. She says:

"Labs and other academic bulidings are literally not built for disabled students, as can be the case for those that have mobility disabilities. Scientists with mental illness or those that are neurodivergent should be believed, listened to, and accommodated for with flexibility and empathy. STEM is exceptionally hostile towards disabled people, especially those living at the intersection of disability and other marginalized groups (race/LGBTQ+ etc.) are hit especially hard, and their voices need to be heard."

You'll find the audio version of Morgan's interview on on our website, Spotify, Google Podcasts, or Soundcloud.

The transcription of our conversation is below, with minor edits for clarity and brevity.

Sound bite:

Morgan Coburn: Disabled people can flourish as much as an abled person can, as long as abled people don't get in the way.

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Asma: Hello world and welcome to Her Royal Science. Thank you so much for joining us for today's episode. Today, we'll be chatting with Morgan Coburn, a graduate student at the University of California – Irvine, who is currently studying the role of human microglia, or resident immune cells, in Alzheimer's disease. Beyond their academic pursuits, she is an active member of the SciComm community, volunteering with UCI’s Center For Learning and Memory, and co-chairing a program called the 'Brain Explorers Academy', in the hopes of getting elementary- and middle-schoolers excited about the brain, about research, and science as a whole. She also advocates for affordable insulin with T1 International, and as an individual in STEM with Type 1 Diabetes, a chronic invisible illness, I hope to speak with her today about her journey, her research, and how ableism in STEM influences her day-to-day life. But let's start from the very beginning. Morgan, what's your story?

Morgan: Should I do my diabetes story or my STEM story?

Asma: We'll start with your STEM story, and then we can... actually, which one do you prefer? We can start with your diabetes story!

Morgan: I actually think that the diabetes and the STEM are intertwined!

Asma: Perfect!

Morgan: I was diagnosed when I was 13, and when you're diagnosed, you are brought into the hospital. You don't know what's going on – there's a lot of tubing attached to you – and you kind of get thrown into the medical world. As a kid, I was always very curious [about] nature, my favourite books and TV shows were National Geographic, so somehow being in the hospital all the time with all these doctors was kind of a fun and interesting experience for me (chuckles) despite being, you know, diagnosed. From that point, I was like, ‘Okay, I'm going to be a doctor’. Then I realized, I don't want to be a doctor.

Asma: (Laughter)

Morgan: As I got older, I learned more about research and I took AP biology and psychology classes in high school. I learned biology, [then] loved biology, and then learned psychology and [I] was like, wait, there's like this little piece called neuroscience! What is that? and decided that is what I wanted to study.

I applied for college. I applied for early decision at one school, because I really wanted to go to Mount Holyoke College, which is a tiny all-women's college on the East Coast.

Asma: Where exactly is that?

Morgan: It's in western Massachusetts.

Asma: [Ah,] okay!

Morgan: So, I got in and started taking more science and neuroscience classes. What really drove home my research interests is I took this neuropharmacology class and there [was] this project that we had to do: pick a compound that modulates someone's brain or behaviour. At the time, I was in a research lab that was studying maternal immune activation in [models of] Autism Spectrum Disorders. I found out about this drug called minocycline. It's a pretty ‘dirty drug’ is what they call it. They have a lot of off-target effects, but it basically will activate microglia inflammation. When they're in an active state, minocycline will come to dampen down the activation.

As I was taking this class [and] doing this project, I realized that this drug, [which is] a tricyclic antibiotic, beyond its antibiotic functions, there were several studies that showed that it was having this really interesting effect with people having a psychiatric illness like schizophrenia and it would help modulate... I'm getting really into this!

Asma: No worries!

Morgan: So, minocycline would help modulate the depressive symptoms that people with schizophrenia experience and many drugs don't do that. Most drugs that are used for the schizophrenic patients affect positive symptoms and those, of course, are very important – positive being the symptoms that are added on to their experience: hallucinations, delusions. Depressive being the symptoms that remove from their experience, so apathy, depression, and catatonia, things like that.

I found it really interesting that no one was studying this, why aren't people looking into the inflammatory system in the brain? For so long, we've said the brain is immune-privileged... there must be something going on. So, with that I applied for graduate school, very convinced [I was] going to study neuroimmunity, this new field that’s absolutely exploding right now.

Asma: I know! Everyone's during microglia at this point!

Morgan: Yes, especially in Alzheimer’s disease, which is what I study here at UCI. I found on my boss, Dr. Blurton-Jones, [who] was just beginning to apply his new in-vitro differentiation model to new systems. As a young grad student, I basically jumped in and started a project. I was transplanting these iPSC microglia, these induced pluripotent stem cell microglia into the brains of very young pups and then they will migrate, differentiate, populate the whole mouse brain and as the mouse ages, you have a human innate immune system within this mouse. When I analysed it, it’s about 80% chimerism and we're actually getting it better with different genetic mouse models. It allows us to look at the human microglial genetic response in a mouse, [and] what we've learned, and other people in the field have learned, that the way that mouse microglia and human microglia respond to stimuli like an amyloid beta plaque, for instance, will look very similar on the surface level, as far as microglial activation. But when you look at the genes, there's a significant genetic divergence between rodents and humans. And, of course, that makes sense. It turns out that, like, a lot of these microglial genes that are different are significantly implicated in Alzheimer's disease.

Many people don't maybe know this, but we've all heard of the genetic risk factors for Alzheimer’s disease. Most of them are in microglia, most of them are enriched in microglia, so it's almost like this disease is being driven and being modulating by microglia. Of course, there is the neuronal component, but there's certain genes that will influence your risk of developing it as much as APOE, for instance: APOE4/4. If you have a mutation in this specific microglial gene called TREM2, that is about the same risk as having one APOE4.

Asma: Wow! Is the risk that high? I was not familiar with that.

Morgan: Yeah, TREM2, the R47H mutation: the risk converts to about one APOE4 allele. And APOE is expressed in microglia too!

Asma: Yes! Very much so. For my own curiosity, are you using mouse models of amyloidosis and then adding in these IPSC microglia?

Morgan: Yeah! We use the 5x animal which just has an over-production of amyloid. That was the first model we tried it out in and it worked beautifully. And these mice, also, I will say are immunodeficient because we are transplanting human cells. Of course, you can't have the mouse's immune system reject it and that comes with its own problems [and] caveats to the model.

Asma: You mentioned as you first talked about your foray into STEM about possibly wanting to go into medicine and be a doctor. What turned you off from that? I feel like so many people that I speak to dabbled in the idea of becoming a clinician and everyone has a different answer as to why they decided it wasn't for them. What's your answer?

Morgan: When I was young, I had a good amount of social anxiety.

Asma: Same here. By the way! (Laughter)

Morgan: Yeah, it's funny – grad school came along and I'm like, I love people now. As I was young, I [thought] I don't really know how I would do talking to patients and if I'm interested in neuroscience too, how devastating would that be, to be the one responsible for, say, for telling patients and family members you have Alzheimer's disease, you have Parkinson’s.

Asma: Yeah.

Morgan: We don't really have good solutions for most neurological disorders and they have devastating side-effects. So, I think that was part of it. I realized that, in neuroscience, you have to deal with really devastating diagnoses. The other side, research, is kind of the cure to that, so to speak. As scientists, we can explore these questions that are still unanswered and empower doctors to heal in the future. So, I really like that aspect of it.

It's fun. I like being in lab. I like handling the rodents and I like doing immunohistochemistry and I like imaging, all the various little things you’ll get into in lab.

Asma: What does ‘a day in the life’ for you, where you're dealing with animal work, [and] you're also doing things in the lab? You can mention some of the work that you're doing outside of the lab too! That seems to keep you quite busy as well.

Morgan: Right now, things have changed because we are in the middle of a pandemic and I am immunocompromised. So, I basically spend most of my time working from home, which has been very sad for me. Pre-pandemic, I would get into lab, [and] check on my mice. Typically, we do these long aging experiments, because we're working with Alzheimer's disease. So, I transplant the day they're born, or the day or so after they're born and let them age 3, 6, 9 months, so oftentimes I don't even need to do rodent work that day.

I will do some imaging, some immunohistochemistry, lots of reading, and planning for future experiments because the length of these experiments are so... they're not quite that long, but they're months long, so I'd like to stagger them so I can be doing something all the time.

But now, basically, I'm working on job applications. I have taken several courses to increase my knowledge of pedagogy – which is the practice of teaching – and that's something that has become more interesting to me. I think in grad school, you're being taught how to do the science part, and not necessarily the teaching part. You do TA, but oftentimes, TAing is grading. UCI has the Department of Education Excellence and Innovation, so they teach you about how to teach a compelling course, essentially, and how to use research – because there is pedagogical research – to inform how you teach. So, what are research peer review backed ways of teaching students and in ways that will be compelling and interesting and keep them excited about school.

They're really, really fun courses and I got interested in pedagogy after volunteering with the Center for Learning and Memory at UCI.

Asma: I did want to go back to something that you talked about briefly: the fact that you are immunocompromised and COVID has taken over the world at this point. I'd like to give you the opportunity to talk about what type 1 diabetes is, if you don’t mind.

Morgan: Yeah. Type 1 diabetes is a chronic autoimmune disease. That means that your immune system looked at your beta cells in your pancreas – which produce insulin – and said, ‘I don't like you anymore. I'm going to kill you.’

Basically, I have a partially functioning organ. I don’t produce insulin or amylin, something people don't talk about. That's the satiety hormone.

Asma: Okay, does that mean you don’t feel hungry?

Morgan: I do feel hungry. I know some type 1 diabetics do experience that symptom though. It's not the only way we experience satiety, or maybe I just have been diagnosed so long, [that] I don't notice it anymore. But insulin is really the big one, because insulin is kind of like the bridge for glucose to get into your cells. [If] you don't have insulin, your body can't metabolize glucose. And of course, glucose is the main thing we metabolize. That's how we get our energy, ATP all that, glycolysis, going back to intro bio!

If you don't have that insulin, instead of metabolizing glucose, you will metabolize fats and that is called ketosis. Many people have heard of the keto diet, [where ketosis] is what you’re trying for. In diabetes, your ketosis turns into ketoacidosis, where you have metabolized so many ketones that your blood has turned into acid and that can be a very deadly condition for people. Maybe we'll get back into that because I want to explain the difference between type 1 diabetes, which is what I have, and type 2 diabetes which I think a lot of people confuse. With T1, I get a lot of, ‘Oh yeah, my uncle has that; he was just diagnosed! I’m like, there is late onset T1 Diabetes, but I don't think we have the same thing.

Type 2 diabetes is more like your body doesn't produce, or your pancreas does not produce enough insulin for your body. Now I want to be careful and say, there's a lot of stigma in type 2 diabetes and it makes me very sad to see people kind of disregard type 2 diabetics as, you did this to yourself. Type 2 diabetes is very genetic and the [number] of socioeconomic factors that play into what food you have access to, it makes me very sad when people say mean things to type 2 diabetics, because they are suffering as much as the type 1 diabetics.

Asma: I agree.

Morgan: So, it basically is a situation where your body doesn't make enough insulin; part of that can be insulin resistance, the foods that you eat can affect how well insulin is signalling in your body. So, if you eat a lot of fatty foods that can lead to insulin resistance. That would mean basically per apple, you would need way more insulin to cover the apple, if you're very resistant to insulin, if that makes sense.

Asma: Yeah, that makes sense. I wanted to know how type 1 diabetes affects your day-to-day life, because obviously the pandemic is a very strange period of time. And I'd love for you to touch upon that a bit more. How that affects you going to the store to pick up things or have you been able to see your family at all as restrictions are starting to lighten up? And then just to juxtapose that with how it affected your day-to-day life in the lab before the pandemic started.

Morgan: Basically, all day I'm thinking about diabetes. It wakes me up in the morning some days, or it puts me to bed very late at night because I'm up watching my blood sugar. So, because of that, sometimes I get a later start than I’d like to. Being in science, we do have, my lab especially, has a pretty flexible [schedule]: come in when you want to, get your work done, leave whenever you want. So, I would roll into lab [around] 10:30 or so and that was never really a problem.

As far as the pandemic, I basically haven't gone to a grocery store; I get all my food delivered. I am very careful to wear masks, wash my hands. I have seen my family a couple times, but from a distance. I've been basically totally isolating myself since March 19. And I have a partner, so he and I will see each other because he's doing basically the same thing for me, and I have a roommate as well, so it's not total social isolation.

I don't go into lab as much and partially because California has had a pretty bad resurgence. It's been very frustrating as someone with a chronic illness to watch the rest of the world, kind of, say, ‘oh whatever, I'm just going to go. It’s just one drink. I'm just gonna go to the bar. Like, I’m healthy.’ Oh, that one makes me so mad. ‘I’m healthy; it doesn’t matter.’ That basically tells me your life doesn't matter because you're disabled; you're chronically ill.

Asma: Yeah, I mean what you were talking about with people saying, ‘well, I'm healthy. I can do whatever I want’ is just the description of ableism and that's not only pervasive in North American society – because I don't think Canadians are absolved of that – but I think it's also pervasive in STEM. Is that something that you've noticed, not necessarily in your lab, but in the science community, [and] in the STEM community that you're a part of?

Morgan: Yes, definitely. I think, partially, I was part of that ableist community because I have an invisible illness and for a while it was something I just put in the back of my brain and dealt with, but never really embraced it as part of myself. So, I lived my life as though I was not chronically ill and that is a problem and became a problem in STEM when I was essentially working myself in and out of the ER and urgent care.

Asma: Oh, my goodness.

Morgan: Yeah, I got to a point where I was having these recurrent kidney infections. Your kidneys are partially responsible for titrating the amount of glucose in your blood and removing it from your blood into your urine and they can only really titrate that amount of blood under 180 milligrams per deciliter. If your blood sugar is consistently high, which mine was because I was in lab all day, I had gloves on, and slowly, my control was slipping away from me as I was working harder and harder in lab. I don’t know if you've ever had a kidney infection, but those are exceptionally painful.

Asma: Oh, I'm sorry to hear that.

Morgan: I was in and out of the ER and urgent care and started to realize, I am killing myself. My A1C, which is a measure of your average glucose essentially over three-month period, was higher than it ever had been and I didn't know why. I hadn't really changed my diet or I was walking three miles a day, essentially, to work and back. But not paying attention at work was leading to these health concerns and I think a lot of people in STEM put their mind first. They put their brain over their body.

And science, I think, is very divorced from your human person. We give accolades to the scientists that have worked their bodies into the ground essentially. It’s a good thing if you're in lab from 11 to 11, or even before that, you know, all day, all night. And if you aren't doing that, that is not you doing enough. It's accepted in STEM that that's the kind of work mentality you need to have to be one of these really impressive scientists.

People will praise the mind and meanwhile, let their bodies suffer. I wonder how many people throughout their grad career and into faculty have let their health slip away from them while they focus on science. And that, it's just so sad for me, you know? It's so sad for me to watch these incredible scientists let their health be low on the totem pole of what they find important, as someone that does not have great health... I do have great health, but my health is in flux with how I treat it, basically. It’s very responsive.

Asma: Which means that perhaps striking a good work-life balance is, I wouldn't say more important, but is at the forefront of your thoughts and your plans for the day or the week. Would you say that that is the case?

Morgan: Definitely.

Asma: What balance do you think you've been able to strike, especially since you did spend a considerable amount of time in the ER. What do you think you learned and have implemented now?

Morgan: It was kind of funny... I started making these changes, maybe two months before the pandemic changed. I don't know if I really have figured out the best work life balance in STEM, because things kind of shut down, and my health has improved tremendously in this time, [because] that's basically been my main priority. However, I started forgiving myself if I needed to go home early.

Sometimes working really hard in the morning and not paying attention to my morning blood sugar leads to an end of day that is not very fun.

Asma. Mhmm. My last question for you: do you have any words of wisdom for perhaps a graduate student who's just starting out, or maybe a graduate student who might be in the position that you're in, where you have a chronic invisible illness and just needs a few words to get them through the day, something they can think of and something they can remember when things get a little bit tough.

Morgan: Yeah, that's a hard one because STEM is really unfriendly to people with chronic illness and disability. For diabetes, most people have accepted it in their mind as an ‘okay’ chronic illness, and I say that in order to illustrate that there is no hierarchy of chronic illness or disability. Everyone experiences pros and cons to it.

It's really finding a good mentor that will understand, or at least try to empathize with you and finding a community online or in person is so important.

Asma: And you'd say that would mostly be over Twitter or do you think that there are resources that people are not entirely familiar with that they could perhaps utilize?

Morgan: I'm, of course, mostly involved in type 1 diabetes community. Twitter's a really great spot; so is Instagram, and TikTok has funny relatable videos. We have a Discord chat.

I think Twitter is really great because it's kind of like stream of consciousness, but you can also find your people pretty easily. For people that are interested in disability in STEM, there are Twitter accounts: Disabled in STEM is really great. Chronically invisible in STEM is a wonderful account. And a lot of people are speaking about their experiences dealing with their disability in science, and a lot of the times it's not positive. There are positives but people with chronic illness/disability get gaslit all the time. They aren't believed a lot of the time. If you need accommodation, they aren't accommodated until after the issue has happened. So, people will say, ‘Oh, you're going to take advantage of the system.’ And then they fail, of course, and then retroactively, [people say] ‘Okay, now we have to fix this.’ Whereas if you take a moment, listen, work with this student and try to understand what is going on and how you can accommodate them. I think disabled people can flourish as much as an abled person can, as long as abled people don't get in the way.

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