Tyra Lee: Student Researcher and Dedicated Advocate in the Field of Medicine
December 18, 2023
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I’m Ryan Hames and I’m a fourth-year Ph.D. student in my final year. My Ph.D. looks at host-pathogen interactions specifically with regard to tissue-resident macrophages, so I work a lot with macrophages in the spleen and liver to look at how they interact with different bacteria when they enter the bloodstream and how they’re taken up by these organs because they are primarily responsible for clearance of the bacteria from the blood.
During the third year of my undergraduate degree project, I did a lab project with Professor Marco Oggoni. I was doing a lot of cell culture and cell culture infections, like cell invasion assays. I was looking at how different bacterial mutants adhered to and invaded cells. It just so happened that Marco was actually looking for a Ph.D. student at the same time and during this time, I got a taste for the project. Luckily he was reasonably impressed with what I was doing and some of his current Ph.D. students at the time vouched for me; I jumped at the chance because I knew that’s what I wanted to do.
I think it’s the same with a lot of Ph.D. programs in the UK, your project is a continuation of the data and knowledge that previous students in the group have already accumulated. In terms of host-pathogen interactions, we found that in the spleen, there was a subset of macrophages that looked like they had a particularly indispensable role in Streptococcus pneumoniae infection, and my project was carrying on from that. To start, it was a lot of reading through all of the literature; reading any papers that have already been published by the group, and then trying to get a broader context by reading a bit more outside the area.
Marco had some ideas of what I could do to start the project but then after a few months, you start to take the project into your own hands and start looking at the data that you’ve accumulated and think “Where can I go from here?” What’s this showing me? What’s interesting about this data?” So as you get more into the project and you kind of understand it a bit more, it becomes more personalized, then you can steer the project where you want to go.
I started looking at circadian rhythm because one of the previous Ph.D. students studied macrophages in the spleen in response to pneumococcal infection. They then noticed and read some old papers that outlined that there was a differential susceptibility to pneumococcal infection throughout the circadian cycle but the mechanistic cause was largely unknown. This student did a single experiment where he infected mice during the day or night, then looked at the number of bacteria in the spleen at six hours post-infection and saw significant differences between both groups of mice, implying that the spleen’s innate immunity may be under circadian control. It was this experiment that prompted Marco to create a project that looked into a circadian rhythm, host interactions, and pneumococcal infection further and that’s where I started.
I’ve gone as far as I can with the circadian rhythm project now, I like to think it’s coming to its natural end for me but there are some more things I think that could be looked at in a subsequent project. In a nutshell, I saw that mice infected at night developed septicemia earlier than mice infected during the day. I found that this was due to an increase in the number of pneumococci in the spleen and this was because pneumococci were able to replicate to a larger degree in marginal zone metallophilic (splenic) macrophages and then seed into the blood in higher numbers; this causes earlier and more prominent levels of circulating pro-inflammatory cytokines and thus the earlier onset of bacteremia. We could go further and start doing for example some RNA sequencing to further work out why this differential phenotype occurs in these macrophages, which some of Marco’s current Ph.D. students are looking into now.
At the moment I am writing my thesis. I tried to write and finish off any remaining experiments at the same time, which I did manage to do successfully for a little while but I was struggling to write my thesis in the small periods of time I’d get between lab work as it’s hard to get into a flow when you only have 30 minutes or an hour of writing at a time. So I put the writing aside for a while and cracked on with lab experiments to finish those first. This week will be my last in the lab and I’ve already written just under half of my thesis. The plan is to get that finished as soon as possible, as one problem is I’m only funded for three years and I’m now in my fourth year so I’ve got no income at the moment, this is the reason why I want to try and finish as soon as I can despite my love for the project. It’s tricky as well as I want to start applying for jobs, but knowing when is the right time to start applying is hard; I don’t want to apply too early and get offered a job too early if I’m still writing, but I don’t want to leave it too late when I’ve submitted and finished and I’m just waiting to start a job. I thought that maybe I could finish off my thesis and work at the same time as starting a new role but speaking to people who did this reinforced that this was not the right decision for me. It’s also something that a lot of Ph.D. students I know have struggled with in the past. In any case, I know I want to go into Pharmaceuticals as I feel that I have an ideal skillset, and this is where my interests lie; I want to use my expertise to ultimately help the human population as much as possible. I think my ideal job would involve the discovery and development of drugs, preferentially anti-infectives.
The biggest thing is resilience. I think a lot of Ph.D. students and scientists, in general, would say the same. When you first start any kind of lab work, usually it doesn’t work straight away. I was quite lucky in that I had a fair amount of lab experience before my Ph.D. During the summer of my second-year undergraduate degree, I did a project on bacteriophages so along with my third-year project, I already had a year of experience by the time I started the Ph.D. This gave me the experience to know that I wouldn’t get results right away, and this is normal. Experiments don’t work all the time and they definitely don’t always work straight away. A lot of the time is spent optimizing and trying to figure out what’s wrong; it’s a slow process changing one factor at a time, but eventually, you get there and it makes the results so much sweeter when you do the same cell culture assay two times, three times a week, trying to get it to work. I’ve noticed this a lot with undergrads or even new Master’s students/Ph.D. students that believe they aren’t cut out for science or their current position because an assay isn’t working. It’s not the case.
It can be very disheartening, but if you stick with it, eventually you’ll get the results and it’ll be so much more rewarding when you do because you put so much work into it. You’re not any less of a scientist by failing. It’s how you bounce back from that, show resilience, and exercise your problem-solving skills. Science isn’t easy, but eventually, it’ll work.
Often, you may experience results that you didn’t expect, and that can be even better than if the results came out as you initially expected. Because if you don’t expect it, then it’s probably going to be a better finding because if you’ve read around and predicted what you think will happen but then it doesn’t, to me, that’s more interesting. Confirmation of currently accepted theories is important, but the fruition of new, surprising findings to me is even more exciting.
Usually, I get up around half-past six. I very much enjoy my coffee in the morning and it’s one of the first things I look forward to when I wake up. I try to go to the gym about five times a week and normally try to get to the gym around half past seven so I can then be in the lab for nine. I love this routine because I feel like I’ve accomplished something before I’ve got into the office and by the time I get into the lab, I’ve completely woken up and I’m ready to crack on with my first task. I do believe exercise clears my head too and allows me to think about problems in a new light afterward.
A typical day at the moment is mostly spent at the computer, analyzing results. I’ve got a huge dataset at the moment, which I’m trying to go through. I’m trying to pick out what’s interesting and what’s not. Rewind to two years ago in the first or second year of the Ph.D., I was mostly in the lab trying to juggle two or three experiments at the same time. I quickly got better at juggling experiments. So when I first started I’d plan like maybe two experiments for the week and I’d do them on separate days, there’d be a lot of dead time in-between. I then started getting more efficient and was able to interweave the experiments to do tasks for one experiment in the spaces between tasks for other experiments. It was a far cry from when I first started, I spent a lot of the time in my second and third-year running around with a load of times written on the back of my hand doing stuff at the same time. My step count was often way over 10,000 per day!
Mainly I use GraphPad, it’s an absolute godsend because of all the statistical tests that are built-in. I find it really easy to use and once you’ve got an idea about which statistical test you need, you can pick the right sort of test and you can go through the different options, and GraphPad will do the rest. It’s still important to know why it’s picked the test it has though.
I have Google Scholar alerts enabled, I’ve got like three different alerts set up and it’s so easy to use as well. There are so many different options you can put in the advanced search. I get a new alert email every two or three days. Sometimes during my morning routine, I have a look and see if there are any new interesting papers while I eat my breakfast.
I mainly listen to podcasts such as “Microbe talk” which I featured last month.
I like to read too, usually in the evening when I come back from work. I read scientific articles and subscribe to Nature. I can just make myself cup tea and sit down and read through some of the articles. It’s quite nice.
Obviously, I said I like going to the gym fairly often. Occasionally I go climbing and I play rugby most weekends. That’s a lot of fun as well. I’m a very big proponent of a “healthy body, healthy mind.” I generally do think it really helps as if there’s ever a period where I don’t go to the gym or do anything physical, for example, I had COVID in the middle of January. In those ten days without doing any kind of fitness, I just felt drained mentally, like I didn’t have any energy or feel sharp mentally. So I’m definitely trying to keep up with it.
I would say definitely follow your interests. I remember during six forms (high school) and especially through undergraduate too (Bachelor’s degree) as well, there was a fair amount of people that sounded like they were going into science or doing their undergraduate degree because of the opportunity of money afterward and what kind of pay grade they’re going to be on but that’s definitely the wrong reasons to go into science or any discipline in my opinion.
That’s why I’m doing what I enjoy. You don’t want to go into something just because you think you might get a good job at the end of it because you might do and you might be fine because you end up really enjoying it, but at the same time you might be spending two years at sixth form, three to four years at university, and potentially another three years doing a Ph.D. and then all of that was in something that you didn’t really enjoy then you might not get anything out of the end of it and decide to change careers. I believe you need to be very committed to science and enjoy it, especially in the field of academia.
Definitely go follow what you find interesting and the rest will come afterward.
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