In this classic episode of Bringing Chemistry to Life you’ll hear another unique life story that’s led to a super talented scientist doing chemistry that’s changing our world for the better. From a childhood in war-torn Burundi to being one of Fortune Magazine’s nominees of most powerful women, Dr. Mireille Kamariza’s story is one of inspiration and a lesson in resilience and seizing opportunity when it presents itself. Her cross-discipline work has led to the development of a simple and affordable diagnostic test for tuberculosis, which has a real chance of helping address this global health challenge.
Visit https://thermofisher.com/bctl to register for your free Bringing Chemistry to Life T-shirt and https://www.alfa.com/en/chemistry-podcasts/ to access our episode summary sheet, which contains links to recent publications and additional content recommendations for our guest.
Sometimes you feel like you missed an opportunity, or didn’t make the best out of it, or sometimes you feel like life is unfair and doesn’t offer any attractive chance. Then you hear stories like Mireille Kamariza’s and your perspective changes.
This is classic Bringing Chemistry to Life episode, where an incredible personal story is intertwined with great science. Dr. Mireille Kamariza, junior fellow at the Society of Fellows at Harvard University, is driven by her personal experience growing up in war-torn Burundi. She was given the opportunity to move to and study in the U.S., rose to the challenge becoming an expert in biorthogonal chemistry and developed a technology for a highly reliable, yet simple and affordable, detection method for tuberculosis. Now Mireille, nominated as one of Fortune Magazine’s most powerful women, wants to give back and aims at addressing the TB global health crisis thanks to her technology.
While listening to Mireille’s personal story alone is well worth your time, make no mistake, there is great chemistry here. Another brilliant example of chemistry at the interface with biology, where some of the most exciting results in modern science come from.
Dr. Mireille Kamariza 00:06
I want a dye that can work with minimal processing. So I want a dye that anybody can use that my grandmother can use, right?
Paolo 00:19
Dr. Mireille Kamariza focuses on detection of tuberculosis. To take on such a large issue requires determination, resilience, and perspective. Luckily, she's an expert in all three. In this season two episode of Bringing Chemistry to Life, we speak to another member of the Chemical and Engineering News' 2020 Talented 12, about their work and trends in the field. I'm your host, Dr. Paolo Braiuca from Thermo Fisher Scientific. We began by asking Dr. Kamariza, about her homeland, and how she found her career in science.
Dr. Mireille Kamariza 00:56
So I was born in a small country called Burundi in East Africa. It's a landlocked country, right at the heart of Africa. And it is a war torn country. And so when I was growing up very early, you know, in my life, the idea of doing science was was far from my mind. I was, however curious. I was particularly curious about the sky and what was behind the sky. And, you know, as with any four or five year old, you go outside, you play, you see animals, and then you look up and you see stars or something, if it's at night. And I wonder, and I used to wonder a lot about what's on those stars, like, Can I walk there? Can I get the kind of fly there? Right. But that was the about the extent of it. My life, my life was surrounded by chaos, right? Like the country was, in the early 90s, my country went through a huge turmoil. And we had to, to flee my country, and we had to move to a different country. And so like, all the issues coming, you know, going with being a refugee in another country and assimilating in another culture. And eventually we, I was fortunate that my family, my my siblings, rather, and I, we ended up moving to the United States. It's fair to say that my life before, my life after, drastically changed. When I moved here, I still didn't really think about being a scientist. It's not a dream, that is part of the landscape for African immigrants who are in the US, right? It's, there aren't many role models. But I had a really curious mind, and I had an inclination towards the sciences. And so when I, when I was privileged enough to be in school, at a community college, I took a lot of science courses. And I'm very fortunate that one of my early chemistry teachers took a likely liking to me and believed in my potential. And so she's the one who essentially said, I think you're really good scientist, I think you should research I was like, What is research? I don't have time to do that, did I pay? And, and it really was, by way of her mentorship and guidance that I found my way through the door of scientific enterprise.
Paolo 03:30
You know, with someone with such a unique story, like yourself. You know, I think these are important things to kind of discuss about, at least for me, I'm really interested in that. So I just want to go back to the fact that, you know, we were thinking about the luck, the serendipity of your development, and what happened to you meeting the right people and the mentors you you've had in your path, it's been, it's been quite key actually, to do even make you realize that you could be a scientist, right? So when, when was the time when you actually started thinking about planning your scientific career? So when did you realize oh, I could actually do this, like, this is what can be.
Dr. Mireille Kamariza 04:11
A very good question. I so I started coming to college, as you said at the beginning, um, and my mind in community college was, let me just get a degree get a job that pays more than minimum wage. And when I was taking the science courses, I, you know, I met with a professor who sort of convinced me that the best way to get a good paying job is to transfer to a four year university and get a bachelor's degree from a from a reputable college. And I was living in San Diego so the school and around me was UC San Diego. So I transferred to UCSD and as part of that transferring process, she said, "You know, there are opportunities to do research. And you can get paid for this. And I think you have the mind to do science. And you know, this is a great opportunity that you should go for." And I did that. And it was an outstanding scholarship program for undergraduates at San Diego that I took advantage of. Somewhere along the way, I, I started liking what I was doing, actually really enjoyed the science I was doing. And I am nearing the end of my undergraduate time, I started contemplating whether just leaving science to get a job somewhere, was really what I was attracted to. I had found my passion now in science, and I knew a lot about molecular biology. And I just wanted to do more of that. I wanted to, honestly, I wanted to stay in acade molecular biology. I still didn't think that I was a scientist, though, I just thought that I liked what I was doing. I didn't know I could go to grad school back then, you know, the universities would have all these like requirements to apply and be admitted to a PhD program. And I just felt that I didn't fit any of any of them. And that would look at past PhD students in different various programs. And none of them had a background like mine. So I really didn't think that this was something that I could do. My mentor at UC San Diego, Tracy Johnson, she is a black woman. And she understood to a deeper level what I was going through. And she used to tell me, and she's like, you know, none of them look like you. But it doesn't mean that you don't belong, right? That you are not going to be just as good as them if you get there. And plus, what does it take for you to apply? Honestly, like, what's gonna take out of you maybe a couple of weeks putting together materials and then and then you can go on your merry way, if it doesn't work out. You should always shoot your shot. Because if you don't shoot your shot, then you will never know if you could have ever gotten it. As you know, my little shy kid I like timidly put together stuff from believer do this, but I did it anyway. And I got into the same school that she went to grad school. And I think that's what solidified it in me, the fact that she had gone through this first she had come out the other end with a PhD. So that bodes well for me. And so I ended up choosing Berkeley because of that, because that that it was a place that she spoke highly of and she had a great time in and so and it was the California still in the Bay Area. It was just really diverse. And so I was like, You know what, yeah, I think I could do this. I could be a scientist. And I think that was the that was the moment where I thought that I could actually do science that literally comes from my mind.
Paolo 08:16
It's only after then where you actually started developing the type of scientist you would become, right? Because that's, that's where you join Carolyn Bertozzi's lab. That's where you you met proper Chemical Biology and you learn about the biorthogonal chemistry and all these things that basically characterizes all your studies. Am I right?
Dr. Mireille Kamariza 08:37
Correct. I mean, Carolyn Bartozzi is such a force in the field of chemistry generally, and certainly Chemical Biology. I knew of Carolyn before I met her. I was mesmerized by her approach. She was both a chemist and a biologist, she had somehow found a way to make chemistry be useful for biology. And the, as my young eyes saw it back then, and the applications were endless. And it's still true today. And and I remember thinking, Wow, she must have geniuses in her lab. Like all these really smart people working on on really important problems. What I wouldn't give for 15 minutes with her. So this was before I got into Berkeley. And then I got into Berkeley. Um, and of course, my number one person I want to talk to is Carolyn Bertozzi and getting on her calendar was was incredibly tough, or so I heard, because when I emailed she immediately was like, Yes, let's meet let's talk more about TB and all the stuff we could do and, and we had a fantastic conversation about what had been done in the world of at the intersection of Chemical Biology and tuberculosis research, and what was left, you know, what was left to be discovered. And I told her, I remember I told her like, I have a mind to do something that could be directly applicable to the places that I left. And so I, these are the kinds of projects that I'm interested in. And she's like, well, that that's what we'd like to hear. So that's how I joined her lab. Mind you, I still, I was still like, a fan girl for everybody in that group. Because of the work that they were producing. It was so amazing to watch. I felt like I just magically stumbled into this thing that Carolyn at any point is gonna be like, Wait, how come you're here, um. I really didn't feel like I deserve to be there. But Carolyn has this this magical touch of bringing the best out of people. And I felt that. I really did. I felt encouraged. I felt listened to. And she was really interested in the ideas that I was proposing, which sometimes surprised me because even I didn't believe in my own ideas. Um, but she did. And she, she would actually listen and encourage and give me leeway to explore what it is that I wanted to explore.
Paolo 11:25
That's what a great mentor does, right. That's, that's what a great manager does.
Dr. Mireille Kamariza 11:30
Yeah. And I mean, I, you know, I ended up taking my my project in a direction that was vastly different than what she typically does in her lab, right. Like some of my, my work ended up becoming clinical Like I went to South Africa, we did a little clinical trial. And we are doing more clinical trials, because because of the work that I did, and she had never done that before in her lab. And again, that's the beauty of having a great mentor is the fact that she allows her students to explore their, their interests and see what what you can do out of that.
Paolo 12:10
And its time to jump into the science, right? Because now now you have excited maybe, you know, given given a little bit of hint into the importance of it. It's fair, it's fair to let you describe what your project has been so far, and what you're focused on.
Dr. Mireille Kamariza 12:25
Yes, absolutely. So Carolyn's lab is based on this concept of bioorthogonal chemistry. And the idea there is that you have, you can engineer chemistry that can occur in a biological system without disturbing the system. So imagine you want to visualize a particular biomolecule in a cell, you can add onto that biomolecule a tag that will selectively interact with a reporter that you feed into the solution. And, and they will interact together in a way that does not perturb the biological surroundings. And then you can precisely and selectively monitor the biomolecule. That definition, you know that that basis has been a breeding ground for lots of different technologies in lots of different applications. In my case, I use, I leverage this biomolecule culture halos, which is a sugar that is metabolized in mycobacterium tuberculosis, the pathogen that causes tuberculosis, is metabolized and inserted into the cell surface. And so what I what I did, I engineered a trehalose dye, so essentially just put a fluorescent photogenic molecule onto trehalose, and then fed the cells that molecule and that essentially made the cell surface of the mycobacteria glow green under fluorescent microscope.
Paolo 14:19
We hope you're enjoying this episode of Bringing Chemistry to Life. It would really mean the world to us if you shared what you like with a couple of your friends or colleagues. I found a way to spread the word would be requesting or free Bringing Chemistry to Life t-shirt. And if you want to find out more about Mireille and her work, you can download additional information and content recommendations. Stay tuned at the end of the episode for information on how to do it. And now back to our conversation.So is this selective for the mycobacteria because mycobacteria is our explicity using trehalose and metabolizing it and then excreting it on the surface. Is that what makes it selected for that mycobacteria? Or is it this is a dye that is going to kind of bind to several different microorganisms?
Dr. Mireille Kamariza 15:13
Yes and no. So the trehalose, so trehelose is just two glucose, you know connected to each other trehalose molecule is is used in a variety of different ways in a variety of contexts, like plants, use trehalose as a source of energy. In mycobacteria, they have a pathway for that, but they also, in addition to that, have a pathway where they use trehalose as a building block to build the cell wall. So what they do is that lipidate, so they put lipids onto the trehalose, the two glucose molecules, and then these lipidated trehalose then get inserted into the cell surface. And that's sort of like part of the, the complex architecture with a cell surface. That's unique to mycobacteria. So this is a class of organisms that are, that that include mycobacterium tuberculosis, Mycobacterium leprae. So they, they cause lots of wide range of illnesses around the world, and they have this unique ability to lipidate trehalose and put them on a cell surface, it also is what makes them very challenging to tackle is because this lipidated trehalose layer is very thick and waxy and hard to get through.
Paolo 16:33
So you feed the the microbes, the building blocks, they used to build up this outer wall. They they synthesize this like lipid out of it, and then put it in as you know, use it as a break in in their external world. The only difference here is that you actually modified the trehalose with a dye that then makes the cell fluorescent and then you can visualize where the actual cell is. And I suppose the fact that the fact that this only happens if the cell is actually actively building the outside wall, so the cell needs to be alive is this one makes your method different than whatever other colorimetric methods that are out there.
Dr. Mireille Kamariza 17:15
That's right. The trick to the dye that we selected is that the dye itself doesn't fluoresce on its own in aqueous environments, like in water and stuff like that. It only becomes fluorescent when it's in a highly hydrophobic environment. So this unique pathway of trehalose lipidation it when the trehalose disconjugates, so we call it DMN-Tre when DMN-Tre gets inserted into the cells, it gets lipidated by way of the traditional trehalose metabolite pathway, and then inserted to the cell surface. And this whole time during this whole process DMN itself the dye is non fluorescent. But as soon as it gets lipidated and inserted into the cell surface, that's when it turns, fluorescent turns on fluorescence. That's the key change with this dye is the fact that because it there is this turn on step to it, it makes the dye require active metabolism, right? In order for it to work. That's one, and two, it requires that the cells themselves are are alive, that the the cell wall is has integrity and intact. So take it in a broader context that means so that I can tell you, one, is a cell actually actively building it's cell wall. And two, is the cell wall structure intact. And which really means that is the cell alive? And is the cell surface like is the cell there? First of all, is the cell present and is a cell viable? Those are the two things that it tells you at once. And so, because of that key specificity to live cells, it makes this incredibly interesting because then it can tell you if cells are dying in a context of drug treatment. So suppose you have a patient that has TB, they come in, they give you a sample, you use our dye to like, visualize how many TB cells they have. And then you give them a drug. And over the course of their treatment, you just monitor the number of cells that are viable in the sample. And hopefully, what you want to see is that as people are getting treated, the number of cells are viable goes down. That means that they're able to fully cure their illness or at least get rid of the live cells. But if you don't see a change in bacterial load, as we call it, then maybe these dyes are resistant to this drug. And so you can actually detect potentially detect drug resistance much earlier than other other methodologies can. And the only one we have right now to detect a drug resistance is to do culture of the TB samples that you get from patients and culture take takes weeks to get back with this dye you can quickly assess, like, within hours or even within days, if someone has a particular strain of TB that is drug resistant, and you don't need to do one drug at a time, you can do a bunch of drugs at a time you can be a multiplex I assay.
Paolo 20:39
What I like of this whole idea is it's beautiful simplicity. It's super elegant.
Dr. Mireille Kamariza 20:47
Yeah, I will say that this, this isn't an idea that came out of thin air, right, they had lots of work that had been done before my time. But no one had really thought about using this in point of care specific field application. Because my eye was towards I want a dye that can work with minimal processing. So I want a dye that anybody can use, that my grandmother can use, right. And because of how it functions, the dye itself that I have, because it stays dark, up until it meets a TB cell. So all you really need to do is put a drop of the reagent onto the sample. It's as simple as that, and then you wait. So I think, again, is because of my my perspective of trying to find something that could be directly applicable now, as quickly as possible in these environment. And because I had a an understanding of what the resources are in those environments, I was able to try to take a technology that people had built for other sciences, and make that applicable for point of care diagnostics with TB.
Paolo 22:08
Just of sticking on the chemistry, you know, what is DMN? Which is your dye. What does that stand for?
Dr. Mireille Kamariza 22:15
DMN stands for dimethyl naphthylamine. It's a naphthylamine based dye that has this unique feature will be able to sensing the hydrophobicity and its environment, and therefore, quenching or releasing high quantum fluorescence yield. It's not the only dye that can do that. There are other a wide range of environment sensing dyes out there. I think that the key part here was using these classes of environment sensitive probes to be able to build this technology was the most important part.
Paolo 22:58
And how stable and cheap DMN trehalose is? So I guess this is key, right?
Dr. Mireille Kamariza 23:04
Very key. DMN is this really small molecule, easy to make. And it's highly stable at room temperature. And of course in cold temperatures, it's much better. Like I ship my dyes to all my collaborators at room temperature. And it works just fine. It's a highly stable molecule. We we really lucked out on that one.
Paolo 23:29
Well, so so you you brought this to the next level. Right? You mentioned you did clinical studies. So this is demonstrated to work. Is this actually currently used in field diagnostics?
Dr. Mireille Kamariza 23:39
No, So, you know, I got my PhD two years ago. And so I you know, we started the company and about, let me say, close to 10 months after we started the company, as we're just gearing up to do the clinical trials COVID-19 happened. And all the resources that were available for TB research have been rewired for COVID-19. I mean, anything you can think of that could be apply for TB has been used for COVID-19 because now we need to we have a crisis. And for a very young small company that is trying to do something better in the TB space. It was just the worst possible timing. Hopefully we can sort of get back on the train and and do the clinical trial that we've always planned to do, and do, build a drug sensitivity essay that we've always planned to do. Now that the attention, hopefully, the attention, we'll come back to the other infectious disease areas.
Paolo 24:48
Yeah, I wish the best luck for you as well. Because Because, you know, we, you deserve it and, and the world deserves it in a way, because this could potentially change life for a lot of people. So so we all want to see this happening.
Dr. Mireille Kamariza 25:00
Right. Right. Exactly. And I, I do think that there is beauty in, in, in connecting with people in other in other spheres, right? Like connecting with the clinician that has, you know, patients in his ICU or connecting to the community health worker in India who's trying to find the patients and try to diagnose COVID-19, quickly. I think all of those stakeholders are informing the work that we do. And it was vital for COVID-19, it was vital for vaccine development. So I, at least in my view, of see the future of science, being very much in close collaboration with stakeholders outside of scientists.
Paolo 25:58
How do you believe the interaction with scientists coming from other disciplines, right, or even non scientists that are more or less involved in your project? Do you find it easy to interact with them?
Dr. Mireille Kamariza 26:01
I'm very easy to talk to non scientists. And in fact, I make that admission to myself so that I can stay connected to the community. I will say that academia, academia wasn't built that way. It wasn't built to make communicating between scientists and the general public easy. In fact, our language is incredibly complicated. You know, like, it's just, we make it incredibly hard for non scientists to know what it is that we do. There are so many movies out there, where there's an evil scientist or a mad scientist. And I think it's just a reflection of the fact that the the general public doesn't really know what we're doing. And we don't really do a good job at communicating that. And so I try to maintain an open door policy with people who are are not chemists or biochemist, to to listen to them, quite frankly, to just listen to what's going on out there. And what it is that I can do on my end, and to also try to facilitate communications with other scientists, and try to bring that to light, particularly when it comes to social justice as well. This is an important part. And I think, opening the door to understanding how we behave is just similar to how the rest of the population behaves. Makes, makes communicating with everybody much easier.
Paolo 27:27
So what's the future for your technology, OliLux Biosciences and your your diagnostic kit? You know, how far are we from really seeing this applied in, in the places where it is needed the most?
Dr. Mireille Kamariza 27:43
We are working very hard to make this technology available in the field, as soon as possible. What's on the horizon, we are gearing up for clinical trials and building this drug sensitivity essay, we are gearing up to set up collaborations internationally across the globe. And I hope that more people care about TB now. And I hope that listeners out or people who are interested in engaging with us do so. The future is bright, in my in my in my view for the company. I think now that people have an acute sensitivity around infectious disease problems, I hope that the care we have for COVID-19 also transfer to other infectious diseases and understand how they're a major problem they've been in the past and continue to be. And I'm excited to embark on this journey with you know, I'm not a, I wasn't trained as a business person as a as an entrepreneur. But here I am. And I'm excited to embark in this new direction of my career, understanding how to how difficult where the challenges come with trying to take a technology out of academia and make it applicable in society.
Paolo 29:06
And I'm sure there'll be a lot of solutions and smart ideas coming from you. And I am actually gonna keep an eye on what you what you're gonna do in the next few years and hopefully interview you again. So as we come to the end of our chat, which has been brilliant, and by the way, I have one question that I always use to close my interviews. You know, now that you are, at this point of your career, you're going through a lot, and there's still a lot to do. But if you had to stop and look back, what would be one piece of advice you would give to someone else, just starting, right, in their career?
Dr. Mireille Kamariza 29:41
You know, when I look at what my path so far, I think resilience is the word that comes to mind. Um, there's a lot of struggles that I had a lot of challenges and a lot of like, you know, winding roads. And the only key part, like you said, at the very beginning, the only key part was the fact that I saw an opportunity and I was able to leverage that opportunity. And, and that requires resilience, right? Like if you're charting a new path, you have to be resilient. And keep at it. Believe in the work that you're doing and be resilient at it and your own motivations and passions.
Paolo 30:31
That was Dr. Mireille Kamariza, a junior fellow at the Society of 'Fellows at Harvard University, and one of the Chemical and Engineering News' Talented 12. Thanks for joining us for the season two episode of Bringing Chemistry to Life and keep an ear out for more. If you enjoy this conversation, you're sure to enjoy Dr. Kamariza's book, video, podcast, and other content recommendations. Visit thermofisher.com/BCTL to access these recommendations and register for a free Bringing Chemistry to Life t-shirt. You can find the URL in the Episode Notes as well for an easy one click access. This episode was produced by Matt Ferris, Matthew Stock, and Emma-jean Weinstein.