Latest / Rad Chat / E224: Constance Fourny - Brain Cancer Immunology and Life as a PhD Researcher
Transcript
- Naman Julka-Anderson (00:00) Hello everyone and welcome to Rad Chat, founded by me, Naman Julka- Anderson. Jo McNamara Rad Chat Host (00:04) and me, Jo McNamara. So Rad Chat is a forward thinking global knowledge hub where healthcare professionals can advance their expertise in radiotherapy and oncology. Unlike traditional academic resources, we blend real world experience, expert insights, best practice, and of course, most importantly, patient perspectives. Naman Julka-Anderson (00:23) We make advanced knowledge engaging and accessible, supporting continuous learning and professional development without compromising patient care or personal time. By providing insights into both technical skills and career development, helping you progress confidently in your field and shape your professional future. Jo McNamara Rad Chat Host (00:39) Just to let you know, our episodes may contain sensitive and difficult topics that you may find distressing or triggering. Naman Julka-Anderson (00:46) So this episode is part of the education and workforce development series where we are taking a bit of a journey beyond the radiotherapy treatment room and into the world of cancer research. So molecular biology and the science that could ultimately help us understand cancer in new ways. I'm sure you can tell we're both ready to nerd out with this. So we've got a guest here, Constance Fourny whose career has taken her into research and into the fascinating world of PhD study. It's coming to her final year. So her work explores some really interesting questions around proteins, peptides, cell signalling and how cells move. Areas that might sound a long way removed from what happens in a clinic but could ultimately have important implications for our understanding of cancer and how it behaves. Hi Connie, how are you? Constance Fourny (01:31) I'm very good, thanks, how are you? Naman Julka-Anderson (01:33) Good, nice to have you here for your first ever podcast. We're very privileged. Constance Fourny (01:36) Yes, thank you for having me. Jo McNamara (01:37) Yeah. Naman Julka-Anderson (01:40) We were chatting before and you listen to mainly true crimes. This is very different, this kind of podcast. Jo McNamara (01:44) Hahaha Constance Fourny (01:45) Yes, I hope so. Jo McNamara (01:48) Unless it goes really badly, in which case it might be a crime. Constance Fourny (01:53) Hahaha Naman Julka-Anderson (01:54) Hopefully not. But Connie, for anyone who doesn't know who you are or what you do, could you tell us a bit about yourself, please? Constance Fourny (02:00) Sure, so I'm a final year PhD student. I'm in my fourth year. I'm looking specifically at gliomas, so brain cancer, and I focus on the identification of targets for new treatments against brain cancer. Specifically, I look at peptides, little pieces of protein that are expressed on the surface of tumour cells and seeing how the immune system reacts to these proteins. Naman Julka-Anderson (02:29) So peptides are in social media at the moment as something you can Constance Fourny (02:33) Yes. Naman Julka-Anderson (02:33) do to look how is that different to what you're looking at. Constance Fourny (02:35) So what I'm looking at essentially is a natural part of your body and your immune system in general. So in health, essentially your cell will naturally have more protein than it needs or as a way to regulate the amount of proteins that are present inside the cell, it'll use a protein or an enzyme called the proteasome and it'll chop up or degrade these proteins into tiny little fragments of the original sequence called peptides. And most of those last for about 10 seconds inside of the cell and then are degraded. But some of them get transported to the cell surface and they're loading, they're loaded, sorry, on these little molecules called MHC class 1 molecules and they're expressed at the cell surface and essentially your immune system uses these peptides presented at the cell surface to tell, okay, this cell is healthy, this, the proteins that are expressed or the peptides that are expressed at the surface are healthy, normal, regular proteins. But when you're looking at a cancer cell or a cell that's infected by virus, you'll identify peptides that are not part of the regular proteome of the cell. And so we'll trigger an immune response specific for those peptides that will lead to cell death, essentially, or the death of the cell that's dying or cancerous or infected. Jo McNamara (04:15) It sounds absolutely incredible. How did you even get into this field of work? Like, how did you start a PhD on such a small protein? Constance Fourny (04:27) well... I actually never really planned on really going into science at all. I grew up in France. I spent the first like 13 years of my life there. because my mum taught French literature at high school level, that's what I really wanted to get into. And then we moved to the UK. because I had the UK has really incredible science teachers in general, I I started developing more of an interest and one of my A-level biology teachers said, I really think that you'd like studying biomedical science at uni. I think, you you show you have a lot of interesting questions and you're good in the lab and that sort of thing. So then I went and I studied biomedical sciences for my undergrad. And then my second year, we had an immunology module. So everything related to the immune system. And it's, to me, it was very much love at first sight. I just immediately knew that that's what I wanted to get into. So I did my masters in immunology at King's College London. And then, the supervisor that I had for my master's project ended up keeping me on first as a research assistant and then offered me a PhD. So it's been kind of, I feel like I've been very lucky in the sense that everything has just kind of happened really neatly one after the other. But yeah. Naman Julka-Anderson (05:59) What is it like being a PhD student? Constance Fourny (06:01) It feels a little bit surreal sometimes because you know when I was in my undergrad and my masters it seemed so out of reach but now that I'm doing it it's really fantastic. There's definitely a lot of hard days, a lot of days where you doubt yourself and your intelligence and your capabilities but I think the reward that you the sense of accomplishment that you feel when something does work and you actually feel like you're starting to figure things out and get to the bottom of your question, it's very satisfying and fulfilling. And I would say that the success or the, yeah, the accomplishment that you feel definitely outweighs the stress and the bad days and everything. Jo McNamara (06:54) It's funny, isn't it? Because you're essentially doing experiments that you want to fail in some respect because Constance Fourny (07:00) Yeah. Jo McNamara (07:01) you want to rule out all the other variables that other people Constance Fourny (07:05) Mm. Jo McNamara (07:06) will say, well, actually, have you considered this and how great to go? Yes, I have, actually. And we've tested that. Constance Fourny (07:11) Yeah. Yeah. Jo McNamara (07:14) So do you feel resilience is something that you have to kind of have as part of your toolkit for being a PhD student? Constance Fourny (07:22) Yeah, definitely. You have to be resilient and determined. And I think one of my main personality traits is I'm generally quite stubborn. And I think that that's very useful in science, actually, because that means that a million things could fail. And I will try one more thing just to see, you know, because maybe that one thing will work. So definitely resilience and being open to being wrong a lot of the time. Jo McNamara (07:56) Yeah. How's the PhD actually altered the way you think about cancer? Because I've spoken to lots of researchers throughout my career and one of the projects that we were involved in was something called Radiation Reveal and talking to researchers who were lab based sometimes that link to the clinical practice and then again to actual patients. Sometimes Constance Fourny (08:21) Mm-hmm. Jo McNamara (08:21) that's really disconnected. You you're doing something in a Petri dish, but actually how much do you think about the patients that your work could potentially then impact later on in life? Constance Fourny (08:32) I would say because me and another PhD student working both on brain cancer, get, you know, blood samples and tumour samples and we process all of that ourselves. Well, we don't get a lot of patient information, but we get, for example, their date of birth or their age and stuff like that. And actually very recently we had a patient and I checked, you know, their information and I was like, their birthdays in two days. And two days later, I remember I made a point of telling that person like, remember it's the patient's birthday today. I think when you're just receiving cells or, you know, things that other people have processed, it's a lot easier to detach yourself from the individual behind the samples that you're getting. But because we're getting such fresh material, I think we managed to stay really connected to it. Naman Julka-Anderson (09:37) When you say fresh material, what is that? Just so you don't scare anyone listening. Constance Fourny (09:41) Sure. So we get blood about... 20 to 30 mils, so just one tube, and then we get a sample off of a tumour that was removed during surgery anyway. So, you know, it's not like the tumour is being removed so that we can have a bit of it. It's part of normal treatment for the patient and whatever material histopathology won't need for diagnosis, we get to use for experiments. Naman Julka-Anderson (10:14) Does the patient have to consent for that as well? Constance Fourny (10:16) Absolutely. It's, they're given prior to surgery. We have a nurse on site that is unrelated to us. It's just part of the surgery team that we're connected to. She identifies patients that are eligible to take part in our study and she will provide them with an information sheet that details everything we're going to do with the sample, how we're going to process it, what projects specifically it's being used for, sort of all the details that the patient needs. She'll give them a little bit of time to read the information and then come back later, answer any questions and then they sign the consent form. It's a really regulated process and the priority is always, always patient informed consent and patient comfort. Jo McNamara (11:09) Amazing. So, Connie, tell us a little bit about what you found out in your four years. What can we expect without sounding like a VIVA? What can we expect from your final Constance Fourny (11:27) Sure. Jo McNamara (11:29) results? Constance Fourny (11:30) So far, we've gotten a lot of interesting results actually about the mechanisms that cancer has developed to evade the immune system. One of the very, I guess one of the more popular side of cancer research is looking at mutated proteins. So proteins that have a variation from the original wild-type protein and that are only expressed in that cancer type. what we're sort of understanding is the likelihood of mutated peptides, so little protein fragments containing that mutation. How sort of how, how do I word this? The reduced probability of peptides being derived from a mutated part of the protein. So essentially the theory would be that mutations develop specifically in areas of the protein that are less likely to be processed by the proteasome and presented at the cell surface. And this would allow the cancer to survive longer by evading detection by the immune system. Naman Julka-Anderson (12:52) And specifically for gliomas, how would you explain what a glioma is and how this would impact directly in the future? Constance Fourny (13:01) I would say that gliomas are very complicated to study and to treat in general because although the brain is part of you and it's part of your body, it's actually quite an isolated environment from the rest of your body. a lot of immune cells obviously will be infiltrating your tissues and everything, you making sure the cells are healthy and okay. But a lot of immune cells are also in your blood and they enter tissue by circulating to different areas of your body through the blood. And the brain is separated from this main circulatory system by something called the blood brain barrier. It's essentially a lot of cells that form tight junctions. They're very tightly packed together and they really limit what exactly can enter into the brain. And because immune cells are fairly big, they can have a much harder time getting through the blood brain barrier and then dispersing further into the tissue and actually reaching the tumour. I think by identifying these mechanisms in which the tumour evades the immune system further, it will potentially remove one of the or one of the important boundaries or hurdles that treatment encounters. Imagine like you're an immune cell, have to get through, you have to climb this wall to get into the blood brain barrier, then you have to look for the tumour, get into the tumour. If you then reach the tumour and can't identify it as foreign, that's quite big and it would be important to keep in mind for treatment development. Jo McNamara (15:04) And is that the goal that your research will then lead on to targeted therapies specifically for gliomas? Constance Fourny (15:11) Absolutely. The goal, you know, is you can do a lot of things with peptides, actually. You could do something called CAR T cell therapy, chimeric antigen T cell. It's essentially an immune cell that you... genetically engineer to express a specific type of receptor that matches a peptide that you're looking for that will respond specifically to that peptide. You could also do peptide vaccines which are essentially you vaccinate the patient with a number of peptides that you've identified as what we call immunogenic so able to trigger an immune response specific for that cancer and then you train the patient's system as a whole rather than providing them with immune cells that are already specific for the cancer. So there's a few options with what you can do. It's really, I feel like because we look at targets specifically, we're sort of at the foundation bit and then everything else can be built up from that. Naman Julka-Anderson (16:21) The vaccine, obviously a normal vaccine like the Covid vaccine or something that is in predicting that you may get some sort of infection and try and protect you in advance. Do you think Constance Fourny (16:32) Mm-hmm. Naman Julka-Anderson (16:32) that's something that could be in the future that everyone would have a peptide vaccine against gliomas? Big question. Not expecting you to have the answer obviously, but still. Constance Fourny (16:42) Actually, this is a very interesting question and I think that would be very complicated to do because one of the main characteristics of gliomas is how heterogeneous they are not only are they incredibly different between two patients, but different regions of a singular tumour will be different. So a peptide vaccine that would be preventative in this case wouldn't just be about targeting gliomas as a whole, it would be about targeting that specific patient's potential tumour and making sure that you're targeting all of the regions of that patient's tumour. I'm not sure whether preventative treatments for gliomas would be feasible, but I do think that preventative treatments against cancers in general are very important to research into. Very complicated, but very important. Jo McNamara (17:43) We've got there with HPV, haven't we? And who would have thought that, 20, 30 Constance Fourny (17:45) Yeah, yeah, absolutely, absolutely. Jo McNamara (17:48) years ago. In terms of kind of the science that you're doing, what's the process from that to potentially then something that's, you know, clinically being tested on patients? Because there is a lot in the media at the moment, isn't there, about the fact that there isn't funding available for brain cancer research and that, you know, there are specific cancers that maybe get a lot more funding and a lot more attention publicly. You know, so how do you go from the lab to a clinical trial when funding is hard to access? Constance Fourny (18:28) Yeah, looking at rarer cancer types and looking at rare diseases in general is always complicated. Funding, yeah, grants are difficult to obtain when you're looking at those rarer conditions. I do think that because of the way that my lab the things that my lab focuses on, it would just be publications about, you know, have we identified these peptides? Have we identified a sequence that could be used to genetically modify immune cells that can be, you know, then moved on to a clinical trial? Whether at our scale, that's something that we'd be able to do, I'm not. Probably, actually, but I personally haven't seen any of my lab's research go into clinical trials, or at least not by us. It's very much, I think a lot of the time clinical trials are done by these sort of bigger... organisations rather than by smaller groups so unfortunately it's a little bit out of our hands I think. Naman Julka-Anderson (19:53) I like that you still said maybe, that was just stubbornness coming through, like, maybe do it. Maybe that's the next thing for you. Constance Fourny (19:59) mean, you you gotta stay hopeful. That's also another really big part of research, I think. You gotta stay optimistic. Naman Julka-Anderson (20:06) Is there anything since your immunology degree that's really surprised you within this work? Constance Fourny (20:11) Hmm. I would say not necessarily surprised me but rather amazed me is just sometimes you you know, you're looking at individual cells or activation markers or whatever it may be and then you read a little bit more and you get really such a clear idea of how complex everything in the human body is and how even if you take into consideration all of these things there are a million other things that your experiment didn't consider and while I think that that can be intimidating as a part of research, I also think Naman Julka-Anderson (20:54) you Constance Fourny (20:56) it's incredibly beautiful to be able to see the complexity of the human body, you know, just in action. Naman Julka-Anderson (21:05) Is this where AI comes in and does actually look at all those other millions of variables? Constance Fourny (21:09) I think that, of course, you know, AI is an interesting tool for research and I know that a lot of researchers do choose to use it. But I do think that, nothing is capable of making connections quite like human intelligence. Jo McNamara (21:25) I love that. Let's get rid of the computers. We don't need them. But I suppose it. Naman Julka-Anderson (21:30) Yeah, proper mic drop response. Jo McNamara (21:33) But I do. I definitely think that there is something to be said for having that human connection to the sample that you're working with. And like you said, knowing details about the patient and putting those kind of nuances together is just so important. And it obviously it comes across just how passionate you are about your work, but also the feasibility that your work has that could potentially then result in better outcomes for these patients. If there was a patient listening to this episode who had a brain tumour, what would you say about research like yours? Why do you think it's so important that people invest? Constance Fourny (22:15) I would say that it's important for people to invest because research, no matter what disease you're looking into, it's never about the individual. It's you are, as a scientist especially and as doctors, nurses, whatever it may be, you are always serving a greater purpose as pretentious as that sounds, you know, it's, it's so important to keep in mind that you're not just doing this for yourself, you are doing this for the patients that are maybe listening now, every patient that has come before them and every patient that will come after them. Naman Julka-Anderson (23:03) It is important I think to never lose sight of that. I think it's hard to always get that across. think having worked in research or I've worked with or sat next to colleagues who are doing pre-clinical, like it's pretty cool the research but you do kind of sit there and think clinically well I might never see this in my lifetime so what Constance Fourny (23:23) Yeah. Naman Julka-Anderson (23:23) is the point? But then obviously 50 years ago I'm sure there was someone else thinking that and now we have all these amazing innovations so it is difficult and I think... Especially maybe some people who would just want to do the treatment side of things in radiotherapy for example. They're very focused on, well it's the day to day, the treatment, day in day out. But yeah, it's good to have people like you who are thinking outside of that. Jo McNamara (23:45) Is complementing the body of work as well isn't it? Even if it Constance Fourny (23:49) Mm. Jo McNamara (23:49) is just such a small piece within a large clinical trial that potentially it might go to, there will be aspects of your work that contribute to that because it Constance Fourny (24:00) Yes. Jo McNamara (24:00) is that body of work which is so important it can't be underestimated however small the research is if done well. Constance Fourny (24:07) Absolutely. And it can feel very small day to day, know, when you're kind of hunched over a microscope just looking at cells vibing in media. But, you know, I think it's really important every day to remind yourself that, you know. when hundreds of years ago when people were building cathedrals, the people who laid the stones at the very base of the cathedral never got to see it completed. That doesn't mean that their work wasn't important. Naman Julka-Anderson (24:43) Deep. Very, very deep, but I agree. It's a very good way and good outlook on life, I guess. Is there any of the outputs of that you've published or you've kind of got to the point with your thesis that you might want to share that we're allowed to know about from your work? Constance Fourny (25:06) I think at the minute because both of my thesis and potential publications are in the process of being written, it's kind of difficult for me to give clear conclusions and results and stuff like that because everything will change so much as the writing process continues, unfortunately. Naman Julka-Anderson (25:27) Right we tried we tried to get something out it's so easy Constance Fourny (25:29) Hahaha Naman Julka-Anderson (25:31) obviously for us to be like well yeah what's happening but again that is part of research that you shouldn't get to a conclusion before you've done other work and I think that's just me being impatient so Constance Fourny (25:38) Yeah, absolutely. Understandable. Naman Julka-Anderson (25:42) yeah so you've obviously got your thesis deadline VIVA what do you anticipate would be next after that Constance Fourny (25:49) I'm hoping that I can stay in academia. You know, I would really love to keep doing cancer research in an academic setting because I do think it provides such... a unique environment to do research. But I've got a few friends that are going into biotech companies or consultancy or even policy making and all of those also sound very interesting. So I'm kind of keeping an eye out for everything. Naman Julka-Anderson (26:25) So Connie, we always like to end with top tips but before we do that we've got some quickfire questions for you which you may or Constance Fourny (26:31) Go ahead. Naman Julka-Anderson (26:32) may not have seen all of them but just short answers. So we've Constance Fourny (26:35) Mm-hmm. Naman Julka-Anderson (26:36) got six for you. What is your favourite scientific discovery? Constance Fourny (26:41) Scientific discovery. Penicillin. Shout out penicillin. Naman Julka-Anderson (26:46) Nice. Nice. Favorite cancer researcher. Jo McNamara (26:54) This will be hard because you'll have your supervisors listening with baited breath. Naman Julka-Anderson (26:57) yeah. Constance Fourny (26:58) You know, I am going to say the PhD student that I work with, Megan Maloney, that's my favorite cancer researcher. Naman Julka-Anderson (27:06) Obviously after your supervisors like Jo said, but that's What is your, what is the biggest misconception about PhD life? Constance Fourny (27:14) That there's no balance. You can absolutely have a work-life balance, you just have to be strict with yourself. Naman Julka-Anderson (27:21) Favourite piece of lab equipment. Constance Fourny (27:25) Ultra centrifuge. Naman Julka-Anderson (27:28) Okay, I don't know what I expected but still yeah cool. If you weren't a researcher what would you be doing? Constance Fourny (27:38) Maybe I would have gone into teaching French literature after all. Naman Julka-Anderson (27:44) There's still time. Constance Fourny (27:45) Yeah. Shout out Jo McNamara (27:45) Shout out to mum. Naman Julka-Anderson (27:47) Yeah. Constance Fourny (27:47) to mum for the French literature. Naman Julka-Anderson (27:51) And then the last one, one scientific question you'd love to have the answer to. Constance Fourny (28:02) I think. And actually, Megan, my favorite cancer researcher, and I talked about this earlier today. Why do we dream, I think would be an interesting one, which maybe they have answered that and I just haven't been kept in the loop, but you know. Naman Julka-Anderson (28:24) Nice, thank you. And then we always like to end with top tips. I don't know, top tips for any people who might want to do a PhD or any patients listening or other researchers, what have you got for them to take away from your episode? Constance Fourny (28:37) I suppose would probably be because I feel like I said it a few times now, just remember that you're not alone, whether you're a patient or a researcher or a doctor, you're part of a community and both as an individual and as part of that community you're valued and you should remember that. Naman Julka-Anderson (29:01) Amazing. Thank you so much for coming on. I think it's a tip. Constance Fourny (29:02) That wasn't really a tip, but... Naman Julka-Anderson (29:07) Thank you very much. It's been great to have you on. Definitely Constance Fourny (29:10) Thank you. Naman Julka-Anderson (29:10) learnt lots as well. Thanks everyone for listening to Rad Chat with me, Naman Julka-Anderson and Jo McNamara. Naman Julka-Anderson (29:19) You can use this episode as part of our free, continual professional development, accredited content, which offers flexible learning that fits your busy schedule. Just check out the show notes for the reflective questions, links to literature and resources, and a link to complete the form to receive your accredited certificate. Jo McNamara Rad Chat Host (29:35) Stay up to date with the latest radiotherapy and oncology advancements by liking and following us on social media channels and hitting subscribe wherever you get your podcasts. Naman Julka-Anderson (29:45) Join a supportive community designed by professionals who understand the unique challenges of radiotherapy and oncology. Check out our website www.radchat.co.uk. Together we're actively working to improve our profession and make a lasting positive impact on cancer care. Jo McNamara Rad Chat Host (30:11) It goes without saying that we can't achieve this alone. It takes all of us working together to create real change. That's why we value every voice and every contribution. We ask that you listen and learn, spread the word, share your story and if you need to, contact us. Naman Julka-Anderson (30:17) If you like what we're doing, buy us a coffee, keep us caffeinated, go to our website to find out more. Thank you all for listening and take care.