Cell scientist to watch – Pascale Guiton

Dr Pascale Guiton

How did you first become interested in science?

It all started with a plant; when I was in the last year of middle school, I had a biology professor who helped us create a herbarium, and there was this common flower in the Ivory Coast that we passed all the time, but nobody paid attention to it. But doing the herbarium and having to separate the petals of the flower, the sepal, knowing the names of the different structures… something just clicked. And I thought, ‘oh, that's cool; can I know more about these things?’. Also, living in the Ivory Coast, we killed our own chickens, and we had to separate the different organs, essentially dissecting the chicken, and I remember helping with this and learning about the body while doing so, the tendons and bones, internal organs, etc., and just like with the plant, I had this natural curiosity and wanted to know more.

More specifically, how and when did you discover your love of microbiology?

Infectious diseases are one of those things that we live with, and growing up, you had to get vaccinated, and you would hear about diseases like AIDS or tuberculosis on the news, so it's one of those things that is all around you, even if you don't really think about it. This was until I came to the US for college, and I took several microbiology classes. I found the topic really interesting, how there is a whole other world of microbes that we don't see. Microbiology is also at the intersection of so many different scientific fields; you can do a bit of biochemistry, immunology and even physics; you can do whatever you want as you study microbes. So, I just think microbes rule the world; even when we become extinct, they'll still be around, and that is very humbling.

I also want to mention one person, Dr Zehava Eichenbaum, who really pushed me and inspired me to become a microbiologist. When I was an undergraduate, I was looking for a job on campus and saw an advertisement for an undergraduate assistant in the lab. So, I popped into her office (very naively; I had no concept of what an interview was at this stage), and she took a chance on me, probably because I was very enthusiastic and told her I could start in the lab right away. Eventually, little by little, I gained my first proper lab experience, doing bacterial cultures and minipreps to isolate bacterial DNA, etc. At the time, my dad wanted me to be a medical doctor, but Dr Eichenbaum jokingly said that I would waste my brain in medical school and that she would make me a scientist – she really believed in me, which I am really grateful for.

After a postdoc at Stanford University, you then established your lab at California State University East Bay (CSUEB) in 2017. How did you find the transition from postdoc to group leader? Are there any best or most difficult moments?

I would say that the transition was not too bad for me at first. I was quite lucky because when I was a postdoc, I was doing some teaching and working in the lab, back and forth between the two, so I already had experience in balancing research with teaching. However, the hardest part was doing all the things behind the scenes that you don't know about, for example, all the paperwork. But I remember when I first saw my lab space, and that feeling of excitement and dread simultaneously. Until then, I had been in labs that were pretty established. But I started thinking ‘I'm going to have to pay for all these things’. I did have a startup package, but as East Bay is a teaching institution, it wasn't as high as you would expect compared to research-intensive institutions. At the same time, I was teaching three courses, one of which I had to develop for 140 students. It was quite daunting; I was also sitting on departmental and college committees, advising student clubs, writing grants, mentoring students in the lab, etc. Then, as I became more established, I had more people in my lab to look after, more students to teach and more grants to write. So, it is learning to balance these responsibilities that is the biggest challenge, but it's what you need to do to be an effective teacher, a productive scientist and a good research mentor.

You have since moved your lab to Santa Clara University, where your research focuses on the microbe Toxoplasma gondii. What are the main questions your lab is trying to answer?

The main question of my research program is ‘how does Toxoplasma initiate infection in a new host?’. Part of that is asking ‘what are the molecular mechanisms that the parasite uses to interact with the gastrointestinal tract?’ Toxoplasma can infect orally using two forms, the product of sexual reproduction (the oocyst) that eventually sporulate to produce infectious sporozoites, which you can ingest from cat faeces or contaminated vegetables or water. The second form that can initiate infection is the chronic form (the bradyzoite) found in tissue cysts in undercooked meat from chronically infected animals. I am focusing on bradyzoites because sporozoites are highly infectious, difficult to keep in the lab and expensive, especially at a primarily undergraduate institution. With bradyzoites, however, we can look at them in vitro and in mice and they can be easily deactivated.

We are tackling this main question from several different angles. Firstly, by trying to identify novel virulence determinants that are required specifically for that first stage of infection. Secondly, we want to understand how Toxoplasma goes from a metabolically fast form (tachyzoite, during the acute phase of infection) where it divides rapidly, to a ‘slow’ form (bradyzoite) that divides slowly and is present during chronic infection. During this lifecycle, Toxoplasma also undergoes transcriptional changes, so I am also looking at the transcriptional regulation in the parasite and how this affects its metabolism and virulence. I am collaborating with Professor Scott Roy at San Francisco State, an evolutionary biologist, who is interested in alternative splicing, and he is trying to find unique splicing features of Toxoplasma. Another feature of Toxoplasma is the presence of specialized secretory organelles (micronemes, rhoptries and dense granules) found in the apical complex. However, how proteins are trafficked to these organelles is not known, and is something we also hope to uncover. Finally, and most recently, we have become interested in understanding the interactions of Toxoplasma with mucus. When you ingest Toxoplasma, it has to get through the microbiota, cross the mucous layer, get to the epithelium, cross the epithelium, find its way into the blood, and then into the brain and skeletal muscles. But I never really paused and thought about the impact of mucus on that initial infection until I taught immunology. And so, now I'm interested in looking at the interaction of Toxoplasma with goblet cells. We just started this project, which I am very excited about. Clearly, I am not very focused and have lots of questions, but I now have teams of undergraduate students working on each of these questions.

You mentioned that being at a teaching institute, your lab is primarily made up of undergraduate students. How does this impact on your research?

Being at an undergraduate institution, I don't see my science as ‘I need to get data, I need to publish’ but more as an extension of my teaching. So in a way, the techniques we use are a bit more basic and the students need to learn how to perform them. For example, if we need to make some knockout lines, I have to teach them about bacterial growth, aseptic technique, PCR, gel electrophoresis, CRISPR-Cas9, etc., which is time-consuming. But I enjoy that, and it's about reinforcing the students' skills and getting the data is almost a result of the students learning those things. So, there are obviously risks with this approach, and the progress can be slow (well it is slow), but I find teaching science and how to do it so rewarding that this is my primary focus.

You are clearly very passionate about education – what are your approaches to teaching?

My approach to effective teaching and learning is akin to manoeuvring a railway handcar whereby both learner and teacher work as partners in an environment conducive to learning. I strongly believe that with the active participation of both individuals, we can: (1) identify and use evidence-based pedagogical approaches to support student learning; (2) establish clear expectations in and outside the classroom; (3) equip students with knowledge and skills, such as critical thinking, writing and organizational abilities; (4) ignite students' curiosity and creativity; and (5) empower them to share their ideas and learn from the diverse community in the classroom. My primary objective is to fully engage my students so that they can acquire these values and skills that transcend degree requirements, as they are lifelong proficiencies applicable to other aspects of their lives.

If you could research something other than parasitology, what would you research and why?

That's a challenging one. I always say if I had to do it all over again, I would be a marine microbiologist. It's fascinating how we (or rather I) know so little about microorganisms in the oceans or their interactions with sea creatures. Outside of microbiology, I would probably be interested in understanding the psychology of dogs. I have a dog who I think has a lot of ‘attitude and opinions’. It would be super cool to know how they approach their relationship with their owners.

Outside of the lab, I see that you are involved in a number of organisations that promote inclusivity and diversity in science, including being a co-founder of the Alliance for the Black Community (ABC). Could you tell us a little about this group and its aims?

I started it with a former colleague at East Bay, Dr Nazzy Pakpour, in response to the lacklustre response that we got from the administration after the George Floyd murder. I don't know why, but something about how the university administration addressed it wasn't quite satisfying to me. First of all, it was on the news for a long time, and we didn't even get any acknowledgment until everybody else had acknowledged it, and the message was so platonic; it didn't even have the word ‘Black’ in it or ‘African American’, if I remember correctly; it was very generic and referred to the ‘minority’. So, we decided to write a letter to our Black student community, which hundreds of faculty members signed, saying that we see them, we hear them and we're here for them.

This was what ignited the rebellious activist side of me that I had repressed for a long time. I couldn't deal with the racism in academia anymore and I wanted to do more, which is where the ABC stemmed from, and we have three main goals: to create infrastructure or communities where we can increase the hiring, retention and promotion of Black faculty and Black staff, as well as the success of Black students; to expand the cultural competency of our faculty around issues of anti-blackness and racism; and the lastly to demilitarize campus police and eliminate racial discrimination by police. Although I understand they need to be there, the amount of money that goes into supporting the police is very distressing, and I think this money needs to be put into advising and counselling services for students. We can put resources into infrastructures that are actually supporting education, which is what we are there for. Especially since the pandemic, there has been a lot of depression and a lot of anxiety among students, and the funding for the support they need just isn't there.

Ultimately, the goal of the ABC is to make academia a place where people that look like me feel like they belong, and can succeed without having to go through all the hoops I did and all the stress. To reflect the changes we want to make, we recently changed the name of the group to Action for the Black Community in Higher Ed; still ABC, but with a little more ‘oomph’. Our motto is ‘talk less, do more’, and we want to show that we are making these changes, not just talking about them.

Another group you are involved with is ‘Black, Indigenous and People of Color (BIPOC) in Parasitology’. How did this come about?

During the pandemic, a grassroots group, Black in Microbiology, was started and we had a dedicated ‘week of Black in Microbiology’, where Black scientists and Black trainees presented their work. One of the reasons for this was the lack of representation of Black scientists at conferences; you may only see one or two Black people presenting. So this group is trying to bring out the contribution of current Black scientists and Black trainees to the forefront. Then, with my friend, Dr Sabrina Absalon (who is French with Algerian heritage), we started BIPOC in Parasitology (BiP), to really get at the point that parasitology is very global and usually encompasses tropical diseases. So, we want to actually hear from people from those areas, and so that's what we're doing. We have a monthly seminar, and it's only faculty and scientists of colour who present. We recently changed our name to PEERs in Parasitology, with PEERs standing for Persons (currently and) historically Excluded from science because of Ethnicity and/or Race. We have many projects underway and rapidly growing.

Finally, could you tell us an interesting fact about yourself that people wouldn't know by looking at your CV?

Some people may not know this, but I was diagnosed with bipolar disorder. Before I was diagnosed, I could stay up for 3 days in a row, no sleep, just working, and I thought I was superwoman. I got my stuff done and I was most productive during those periods. Although I don't stay up like that anymore, one quirk to having this condition is I can still be very effective at my work! It has also been empowering to be able to talk openly about my mental health; it helps reduce the stigma. And this reality makes me a much more empathic individual, especially towards my students. Anxiety and depression are quite high among college students.

One other thing, which is less of a fact and more of a story, is that when I was a graduate student, so for 4 years, I played rugby, and I was selected to represent the West Conference. But 7 minutes into the game, I tore a ligament in my knee, my MCL. And it's not like I was going to be selected, but the US rugby coach was there, and I obviously wasn't going to make it after that!

Pascale Guiton was interviewed by Daniel Routledge, Cross-title Reviews Editor at The Company of Biologists. This piece has been edited and condensed with approval from the interviewee.