Interview by Sanchutha Sathiananthamoorthy and Marie-Belle El Mdawar
Featuring in the première of our ECR spotlight series are two early career researchers; Dr Masahiro Yoshida and Miss Kaylee Worlock, who discuss their recently published frontline research on immune response to SARS-CoV-2 infection in children and adults. They reflect on the highlights of their research careers thus far and share some of their favourite pastimes, whilst also describing some relatable moments when the going gets tough!
Masahiro Yoshida is a medical doctor from Japan who joined UCL Respiratory department in 2019 as a Research Fellow in Respiratory Cell Biology. Recently, he won a Medical Research award from the Tokyo Medical Association.
Kaylee Worlock is a 2nd year PhD student at UCL Respiratory. She was awarded a MRC DTP (Medical Research Council Doctoral Training Partnership) research studentship to undertake her PhD project. (Photography by Dr Pascal Durrenberger pfdphotographie.com, Twitter: @pfdphotographie)
Over the past 6 months, Kaylee and Masahiro were fully implicated in studies on COVID-19. They recently published a preprint: 'The local and systemic response to SARS-CoV-2 infection in children and adults' and provided data in a collaborative study published in Nature Medicine: Single-cell multi-omics analysis of the immune response in COVID-19.
1. What led you to a research career in Sciences?
Masahiro: I am a qualified medical doctor in Japan. I did some clinical work as respiratory physician in Japanese hospital so I was confronted first line with patients having respiratory diseases, most of them being incurable with no available treatment. That is why I was interested in being a scientist to find new ways to treat patients with chronic lung diseases. I also followed my boss’s advice that “every respiratory clinician should be a scientist”.
Kaylee: I always found science interesting since I was young, and I kept pursuing it at the university. I like the constant learning side of being a scientist, which attracts me to this area and the fact that the work has a real-life implication.
2. You recently published research about the immune response in COVID-19 patients. What is the motivation behind your project?
Kaylee: The pandemic for sure! I was already collecting pediatric samples, with a pipeline established with GOSH [Great Ormond Street Hospital for children] and the Wellcome Sanger Institute to study airway development in fetal and pediatric lungs. So, it went hand in hand looking at why children seem to have less severe form of the COVID-19 disease, and less prevalence. That is how the project kicked-off.
Masahiro added: we were always looking to do some research that have impact on people’s life, so to investigate this during the pandemic felt good to help understand what is happening.
3. What were the main findings of your study? And how will this impact the management of COVID-19?
Kaylee: One powerful part of our study, in my opinion, is the matched blood and airway epithelium we were able to collect, with a cohort of 30 healthy pediatric cases from neonatal to adolescence. Although there are some studies that have looked onto characterizing this, few have matched samples, or that number of samples and the granularity. In most of studies, they [the samples] are used only as controls to look at a particular disease, so understanding the main development was key, and I hope it will provide a good resource for other future studies. In our study, we used this dataset to try and better understand the difference in children and adults in terms of COVID-19. We saw the overall immune response reflected that underlying the immune landscape in children and adults, with a stronger innate immune response in children compared to a more adaptive response in adults, which has been described in the literature. Interestingly, we also saw a notable difference in the immune response between the nasal cells and in the blood; this is another strong point of the study showing the importance of looking at both the site of infection and systemically. By understanding why children present with less severity, we can perhaps use that to help guide the treatments in clinic.
Masahiro: In the Nature Medicine paper, we did single cell transcriptomics, surface proteome analysis and TCR/BCR receptor analysis of COVID-19 samples in peripheral blood. It was a collaborative work across UK (three centres: Newcastle, Cambridge, London) with 130 patients in this cohort, which is a large number providing a good resource for further translational research using this data set. In the preprint paper, we used the same techniques, and we collected more samples that we will add to the study.
4. What is the most amazing thing about lungs that people may not know?
Kaylee: It is difficult to say what people may or may not know. I think that fact that around 20% of cell composition of the lungs are immune cells, it is a large number! Also, lungs continue to develop in adults. We used to think that lung development stops at 3 years old, but a recent study has suggested that alveoli continue to develop up to 21 years!
Masahiro: For me it is the complex structure of the lungs with endothelial, epithelial and mesenchymal cells that allow the air exchange. That is why it is hard to reproduce this environment to study lung development and regeneration.
5. What are you currently working on in the lab? And what are your next steps?
Masahiro: I am working on lung development especially immune-epithelial interactions. This project was postponed during the pandemic and now I will be able to address it again.
Kaylee: Since we have the single cell data [of samples collected for the studies], it will be interesting to do some in vitro assays looking to the maturity of immune cells and how they affect epithelial cells over development.
6. Can you speak to any setback that you have encountered as a researcher and how you overcame it?
Kaylee: When I was applying for PhDs, I applied for quite a few with rejections so perseverance and projection are important. If I had to do it again, I will not be doing it at the same time as I was preparing my exams, it was stressful. Also, I am not a big fan of writing, so I am still trying to overcome that, particularly now since I am writing my upgrade.
Masahiro: The science is about testing and most of the times it does not work, and it is about making mistakes and trying again. Back during my PhD in Japan, I had a 4-year project. I did not get any results or mostly failure during the first 2 years. I managed to finish in the second half with only 2 years’ work, learning from my failure. The important thing is to learn from mistakes.
7. Is there an interesting bit of research or review that you have recently read and you want to share with us?
Kaylee: There is quite a few. If I must choose one, there was an interesting study published recently, addressing how apoptotic cells are cleared in the blastula embryo, during the first stages before the immune system is even developed. They [the authors] show that epithelial cells could phagocytose and clear dead cells, facilitating error correction in early embryogenesis.
Masahiro: I would like to highlight the recent ERS monograph edited by Marko [Dr. Marko Nikolic], with people in the lab participating in writing different chapters. It is a comprehensive summary from lung development to regenerative medicine, so we can learn a lot from this book.
8. What are you most proud of attaining or achieving in your research journey?
Kaylee: The papers are definitely something I am really proud of [laughs]. Especially as an undergraduate and when you are at the beginning of your PhD, you are like: everyone is talking about papers! I feel like I am really progressing by getting to that point and I feel like less of an imposter. I think that is really cool. I am also really proud of how much we have done in the last year for the COVID project. I think it is insane to look back and realize that it was just a little more than a year ago.
Masahiro: [Nodding] I am proud of our current work too. Personally, it has been really challenging for me to start a new life/work here [in London]. I was born and raised in Japan and worked around 10 years there. During my PhD work, I wanted to see the world and learn about cutting edge science as well as different cultures. I was actually struggling at first: my English is not perfect, but I really like this environment and I am very grateful for all the things [I have] right now. I am really proud of my choice to go overseas.
9. Do you have any advice for PhD students or for students who are embarking on their PhD journey?
Kaylee: I was lucky enough to get onto the UCL DTP [Doctoral Training Partnership] program, where I got to do rotations beforehand [before starting PhD project]. I think that really benefitted me. I was able to try a few different things and really pick out what I wanted. Before I went [to different labs], I did not really know exactly what area of research I wanted to do. I knew cellular and molecular biology was something I was interested in, but other than that, I was not too sure; lungs were not really an area that I had properly looked at before. So, trying a few things was definitely a huge advantage for me, and allowed [me] to look at the actual lab environment rather than just solely the project. I think I have been really lucky. Marko [Dr. Marko Nikolic] is an excellent supervisor and the whole lab is just so nice and friendly, the whole respiratory floor always helped me so far in the PhD and I cannot imagine not doing one [a PhD project] without such a supportive environment. So, I think that is a key thing to think about as well as what you want to do and what you are interested in, like picking out a lab where you are comfortable and supported.
Masahiro: In the long PhD journey, going forwards, you might face many difficulties, many failures, as I experienced, but I think it is really important to learn from that. I also think it is really important to be interested in your project and really like your project and that can lead to good results.
10. In the time that you have been here, can you name one thing or aspect that you like about UCL?
Kaylee: I like how connected everything is. There are three/four hospitals all round [UCL] and connections between the two [university and hospitals], as well as the collaborations between all the other universities. So [for example], we go to King’s college for imaging and are collaborating in projects with Imperial College and the Wellcome Sanger Institute. I really like the collaborative nature that UCL seems to have for research here, although I am sure it is the same for other universities! [laughs].
Masahiro: I think the situation here [in London] is totally different from Japan. In general, it is really competitive between the universities [in Tokyo] and as Kaylee said, [at UCL] we are working with King’s College London. It is surprising for me as the situation is different in Japan. I really like this progression and the sharing of lots of expertise in London, and lots of resources, it is really nice [to work in this environment].
11. Do you have a favourite research skill, expertise or experience that you are most proud of as a researcher?
Masahiro: Me and Kaylee both processed over 150 samples for single-cell sequencing [for the COVID-19 project].
Kaylee: [Confirming] I am very proud of how quickly we picked it up, although the 10X Genomics [Technological approach] is designed for biologists who have never done it before, but I think I am proud of how quickly we have progressed. I think Masahiro is very good at imaging. [He has] all those beautiful images of sections staining and whole mount staining, I would say that is one of his skills. They always look so pretty!
Masahiro: Yes, I really like to get images. My goal is to make it to the covers of journals!
12. When you are not working in the lab and not doing research, what is your favourite non-research thing to do?
Kaylee: I used to do some climbing. I was trying to get into some bouldering. Everyone seems to pick up climbing around London [laughs] so I was trying to do that. I think that was quite fun. I used to have hobbies! [before lockdown].
Masahiro: I like travelling. My second goal in the UK is to travel around Europe, because it was really expensive to travel around the EU from Japan! But it is really close to here [from London]. So, after the pandemic, I will restart travelling around the EU. Recently, I was travelling with my family including my son, so that was a really nice time for me.
13. In recent years, the importance of mental health has taken center stage. During this time, it has certainly been a challenge for people to preserve their mental health and wellbeing. Is there something that you do to look after your mental health during these trying times or as a researcher in general?
Kaylee: In my final year at university, while I was writing my dissertation, I got very stressed, I did not have a very good time. Since then I have been trying to [when I get overly stressed] step back and realize that it is not the be-all or end-all. Although at the time it was very hard to do that! I try to go for walks or just do something that reminds me that there is other stuff going on and if I cannot get this thing to work or if I cannot write this essay, things are not going to fall down around me. I think having good friends and having people that you can fall back on as well helps a lot with that
Masahiro: Back in my PhD years, I was also a medical doctor so I was really busy in the daytime from Monday to Saturday in clinical settings, and after maybe 6 or 7 pm, I was doing my lab work. That was really busy and stressful. But on Sunday I was off, so I was trying to totally switch off and unwind. It was important for me even if it was short. Travelling was the best get away from those duties.
Kaylee: I think it is hard with research [to switch off], there is always more [to do]. There is another paper or there is another thing. I will occasionally do a cull of my [internet browser] tabs when they get to a certain point and I think: it’s not going to happen or not going to happen in the next couple of days anyway. So, I will just have to go through and delete all the ones I don’t need, and save the ones I need for later! [laughs].
That is why mine [laptop] is getting really hot at the moment. It is getting to the point where there are too many tabs open and I will just have to give them the cull!
14. In the spirit of spreading positivity. Do you have a positive word, phrase or affirmation that you would like to share?
Masahiro: I have something in Japanese which translates into English as: ‘Efforts never betray’.
Kaylee: My Mum sends me a lot of quotes [laughs]. The most recent one is: ‘Never give up, for that is just the place and time that the tide will turn’.
Useful links
- Early Career Research Network
- UCL Respiratory
- Division of Medicine
