The PAM Talks
Transcript: Paula Brandt
Paula Brandt - Exploring the Intersection of Physics and Medicine
Paula Brandt: I started getting the nagging feeling that I wanted to go back to medicine, and I thought, I'm loving my classes, I don't want to switch to medicine, let me see if I can combine these two passions of mine. So I set myself out looking for labs to join, and luckily I found this one that just combines my interests so wonderfully, and I'm so grateful to be a part of the lab I'm in.
Gabby Gelinas: Welcome to The PAM Talks. Each episode, we interview a new physics and astronomy mentor exploring the universe through the lens of diversity. I am Gabby, and today I will be your host. I am a master's student at the University of British Columbia. For this episode of the PAM Talks, we will be interviewing Paula Brandt, a medical science PhD student at the University of Calgary.
Paula began her academic journey as a undergraduate student at the University of Calgary, where she completed a bachelor of physics with a minor in biology. Paula's background in physics gave her exemplary coding and data analysis skills and the knowledge to push her research farther than she could have otherwise due to her optics background. Today, we will be discussing Paula's work studying protein misfolding in type 2 diabetes. We will be learning more about the need for this innovation in the field and how this can impact the lives of so many different people.
This is the PAM Talks, where the universe is as diverse as the minds that are unraveling it. Coming up next, my interview with Paula.
GG: Hi, everyone, I'm Gabby, and today I'm here with Paula Brandt. Paula will be telling us about her work studying the islet amyloid polypeptide in connection to type 2 diabetes amyloids. Paula, welcome to the PAM Talks.
PB: Thank you, I'm excited to be here.
GG: So, Paula, this protein, I don't have a medical background, I'm not familiar with it. What does it do? Why is it interesting to you?
PB: So the protein that I'm looking at is called islet amyloid polypeptide, and this is a protein that is implicated in type 2 diabetes. So when most people think of type 2 diabetes, they think of insulin. But actually this protein, islet amyloid polypeptide, which I will shorten to IAPP because it's a bit of a mouthful to say, is actually cosecreted along with insulin. So it comes out of the islet cells in the pancreas at the same time as insulin does. So this protein is pretty much just as important as insulin in diabetes, but not many people know about it.
So in type 2 diabetes, this protein actually has a tendency to misfold. And this is a problem because proteins are important for a whole bunch of different things in the body. They allow different nutrients to enter cells, leave cells, clear out waste. They're really quite important. And when a protein is not in its proper shape, it can either not do its job properly or it can become toxic. And that's what happens with IAPP. It actually becomes toxic and it attacks the cells in the pancreas that produce insulin. So this protein kind of sits on the islet cells and causes them to essentially die off.
So in this scenario, you're not producing enough insulin, which lowers blood sugar. And if you have type 2 diabetes, controlling your blood sugar is extremely important. And it's already difficult to do, especially in type 2 diabetes, people usually are resistant to insulin already. So the insulin is not able to enter their cells and lower their blood sugar, which causes a lot of problems already. And then this protein comes along and attacks the islet cells that produce insulin. So this makes the body not produce enough of it. And it causes blood sugar to skyrocket and causes a bunch of different problems as well.
GG: So this protein that you're describing now, it seems like, wonderful thing when it works, when it doesn't, honestly seems kind of scary.
PB: So misfolded proteins are actually implicated in Alzheimer's disease as well, which is a condition that most people have heard of. But the concept of misfolded proteins in diabetes is a bit of a new prospect. But we also think that these misfolded proteins get into other organs of the body, especially the kidneys. And since they're toxic in the pancreas, they must be toxic in the kidneys as well, which is the main thing we are looking into in my thesis.
GG: How do we find out if this has happened? How do we identify these misfolded proteins right now?
PB: Right now, the main way to do this is using a stain called the Congo red stain. And unfortunately, you have to wait until the person has passed away in order to do this. And they look at a pancreatic section. So they actually take out a portion of the pancreas and they stain it with this dye called Congo red. And it essentially causes the misfolded proteins to show up in a kind of red colour.
The issue with this dye is that it only shows you that there are these misfolded proteins present. It doesn't tell you what type of protein it is. So for example, people with Alzheimer's also have misfolded proteins. They’re a different type of protein, but they essentially look exactly the same under the microscope. So you could take a pancreatic section from someone with type 2 diabetes and with Alzheimer's disease, and their two types of misfolded proteins from Alzheimer's and diabetes would look exactly the same with this Congo red dye.
And that is essentially what we are trying to fix. Rather than having a two-step method where you detect the protein and then you go through a bunch of additional steps to type it, I am hoping to make this a one-step method where we are able to detect and type the amyloid in a single step so that it is a much faster process. And then hopefully we can get away from doing this in deceased patients as well and actually translate it to either a blood test or a urine test where this can be done in order to inform treatments.
GG: That sounds amazing. So if right now we can only detect it when you're dead, is there any sort of treatment that already exists that your new diagnostic procedure would allow us to put into action? Or would there still need to be additional developments after that to now form a treatment?
PB: For sure, yeah. So the concept of these misfolded proteins in diabetes is actually quite new. Most people think that hyperglycemia or high blood sugar is the driving force behind all of these complications that diabetics experience like kidney damage. They also get some sort of dementia problems as well, a bunch of vascular problems. So right now people are really focused on the hyperglycemia.
However, these misfolded proteins kind of wreaking havoc on the body is a totally new aspect of diabetes that we're looking into. So we really hope that along with controlling the blood sugar, controlling these proteins and their misfolding could open up a brand new way to control diabetes, which would be very cool.
GG: That's amazing. So with your procedure, you can identify this disease sooner while you're alive and still enable treatment. But what would this process look like? So from the time that you're diagnosed with diabetes and you start experiencing these complications, we introduced you to this treatment method. How long do you think that would take to get results or how early would we need to introduce this to be effective?
PB: Absolutely. Yeah, that's a very difficult question to answer right now. From what we know, these misfolded proteins, as soon as they misfold, they cause problems. They initially misfold inside of the cells. And then as they kind of accumulate more misfolded proteins, they're kind of like Velcro. These proteins attract other proteins, and they kind of make really big links, and they cause damage that way, and then they move outside of the cell.
But from what we know, they cause damage at every part of the disease process, essentially. So we would need a very, very accurate way to find these proteins and find them very early, which is of course something we're still working on. But the hope is that we can find these misfolded proteins even before they start causing symptoms, so that we could do some preventative measures as well.
GG: Oh, wow. Okay, so you don't even need to start experiencing any of these negative side effects before you're able to treat them and wipe them out.
PB: That's the hope, that's the hope. This whole world of misfolded proteins and diabetes is not really well studied. So from what we know from other misfolded protein diseases, the proteins misfold before noticeable symptoms start happening. So that is something that we expect to also happen in diabetes as well.
GG: Fascinating. So then once you get their sample in, how long does it take you to actually test these proteins and figure out what they are? What's that process like for figuring out what kind of misfolded proteins these are?
PB: Sure, absolutely. So right now in my work, I receive the pancreatic autopsy sections because we're just working on a really positive control right now. We know there are these misfolded proteins in the pancreas of people who have died with diabetes.
So I'm using that to kind of validate my hypothesis and my experiments right now. So I take those samples, and my staining procedure right now, using these fancy dyes that can detect and type the misfolded proteins in a single step. It takes about 24 hours to do the staining, and then only about an hour or so to do the imaging, which is quite nice. So it doesn't take very long.
GG: Paula, you just keep blowing me away. So Paula, I'd like to switch gears a bit now. And you mentioned that you did your undergraduate degree in physics. Hearing this, most people do not think about physics with what we've been discussing so far. So could you explain how that overlap happened? Where does the physics come into your research?
PB: Definitely. So I've been using the term color pretty loosely here. And that is, in the big picture, what I'm looking at. However, what I'm really looking at when I say color is the emission spectrum of the dye that I'm looking at.
So in a dye molecule, the electrons in the molecule are kind of just happy. They're just hanging out. And then what I do is I hit the dye molecule with a laser. And the electrons see this laser and they get very excited. They kind of absorb the energy that is carried by the laser and they go up to a higher energy level.
So these electrons then, to release back down to the relaxed state where they were at before, and also conserve energy. That's one of the laws of physics. Energy needs to be conserved. They actually emit a photon of light, or you can think of it as a beam of light coming out from the particle.
So this light is actually what I'm looking at. And this light is not just red or green or blue, but it has a very wide range of colors. And so when I look at the spectrum, it's a representation of the amount of light in many different colors that the dye molecule is emitting. And just knowing the physics behind that process has really helped me in choosing the right dye molecules to use, the right color of laser to use in order to get the electrons optimally excited.
GG: Wonderful. I didn't realize how much physics really comes up in medical studies. Like, I always think, okay, physics and medicine, you think MRI. I don't think about developing diagnostic procedures in this style, so it's really neat that that overlap exists. I don't think many other people realize that either.
So when you were going into physics, did you know this was an option to you? Was this a goal for you, or is this something you just learned about along the way and then excelled at?
PB: Absolutely not. So I went into my undergrad really, really torn between medicine and physics. I loved medicine because I loved the applicability of the science. You can use what you know to help people. I really, really liked that. But I was also really into math and physics and just the hard sciences having a right and wrong answer that really appealed to me.
So I was torn. I didn't know what to do. And I actually applied to the Bachelor of Health Sciences at the U of C, and I got rejected. So that was kind of an option that was taken away from me at the start. I was and I had physics as my second choice, and I love both. So I decided I'll just go for physics. We'll see how it goes. And I really, really enjoyed my classes, had an excellent time, you know, first and second year.
Sometime in my second year, I started getting the nagging feeling that I wanted to go back to medicine, and I thought, I'm loving my classes. I don't want to switch to medicine. Let me see if I can combine these two passions of mine. And that's when I started looking for summer work and jobs in a laboratory.
Because at the U of C, there's not a ton of opportunity to combine medicine and physics in your classes. There are plenty of labs that do it, which is amazing. So I set myself out looking for labs to join. And luckily, I found this one that just combines my interests so wonderfully. And I'm so grateful to be a part of the lab I'm in.
GG: Well, I'm sure medicine is really regretting their decision now, but quite happy that they got you back. So what's next? You go through your PhD. After you're finished, are you looking to continue in developing diagnostic procedures? Are you thinking of moving into clinical work?
PB: That's definitely still an open question, I would say. Throughout my PhD, I'm trying to go to as many talks as I can, as many classes as I can, just see what's out there, to see what I'm interested in. I would really, really like to get into the more clinical side of things where I can really use my knowledge in physics and in all these things I'm doing to help people.
So I think the main goal for me is to develop some kind of method. Maybe it's the one I'm working on now. Maybe it's something different in order to make a difference in the way we either diagnose or treat a disease and just somehow become the new gold standard of treating people or diagnosing them. I think that's one of my life goals for sure.
GG: Wonderful. So you really are looking to get the best of both worlds here and just do everything and just save everyone's kidney problems.
PB: Absolutely. I can't say no to anything, it seems like. Everything is interesting, everything is exciting. I can't choose between just physics or medicine. I absolutely want to keep doing both for the rest of my life.
GG: That's so exciting that that exists and you have the chance to do that. So it's clear that even though there's still a lot of work to be done, what you're working on here holds great potential in the field of medical physics or just medicine in general and holds great potential for so many people to have such an improved quality of life. Thinking into medical physics more broadly, what do you see as some of the great promises that are coming up around today?
PB: Definitely. I am super into the field of personalized medicine. So using all these techniques to kind of look at people on an individual level and find an optimal treatment plan or diagnostic test that is good for them, not necessarily for the disease only.
So something really exciting that I have found lately is looking at these pancreases of people with type 2 diabetes. They both have type 2 diabetes, but their amyloid or misfolded proteins look entirely different. So one of my patients with type 2 diabetes, their amyloid deposits look kind of bluish-yellow, and then the other patient, same disease, type 2 diabetes, but their amyloid deposits are much more green.
So it's likely, since they have the same condition, that these proteins are made of the same primary structure. The proteins are the same type, however, they're folded differently. And maybe one person's amyloid is folded tighter than the other, making one progress to some kind of different pathway than the other. Maybe one is much harder to treat than the other, so it needs more aggressive treatment.
Having the same disease needing to be treated two different ways, I think, is a very real scenario for many people, and I'm hoping that my techniques can help with that.
GG: That would be such a fascinating development to see, and I would love to learn more about this. I am always so excited to learn about your work, and I am so, so, so inspired by the work that you're doing here. I am always so impressed by what you were able to accomplish at such an early stage of your career, and seeing the promise that your research holds gets me really excited about the future of medical physics.
Thank you so much for taking the time to join us. So as we head to part, do you have any final words for our listeners about medical physics in general and the great, exciting opportunities that are ahead of us?
PB: So I think my final words don't have much to do with medicine and physics in general, but more about being able to do everything that you want to do in life. I was split between medicine and physics and couldn't choose between the two, but somehow found a way to combine them into something that I really love. And I'm really excited to go into the lab every day and make new exciting discoveries in two fields that I'm so passionate about.
So if there's two or more things that you love, you can find some way to combine them. I'm confident of that. And just don't take no for an answer is also a good life motto.
GG: Great, thank you so much, Paula. And thank you for coming on the PAM Talks. Please stay tuned for our next episode and get ready to explore the universe through the lens of diversity and join us in celebrating the brilliant minds breaking barriers in physics and astronomy.
The PAM Talks gratefully acknowledges the support from the University of Calgary Graduate Association Quality Money Grant Programs.
And do you have any final words to our viewers about the power of kidneys?
PB: Look after your kidneys. They're really important. You can live without one, but you can't live without two. That's all I got. GG: I feel like that was bad. That was so awkward. I said the power of kidneys. Thanks Paula, so much for coming on. All right, that has been the PAM Talks. Thank you all. Goodbye.
Transcript copied and edited from Apple Podcasts