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Ph.D. defence interview - Caroline Haikal

Profile photo of Caroline Haikal and the thesis cover. Photo Collage.
Caroline Haikal defends her thesis on the 11th of March 2022.

During her Ph.D. studies, Caroline Haikal has investigated the connections between the gut and the brain in early Parkinson’s disease development. On March 11, she defends her work supervised by Prof. Jia-Yi Li. Here, Caroline tells us about her research in Neural Plasticity and Repair, one of MultiPark’s experimental research groups.

Tell us about your research!

My research is about the connections between the gut and the brain when it comes to alpha-synuclein, a protein known to aggregate in patients with Parkinson’s disease. When I started my thesis project, it was already known that this protein s expressed not only in the central nervous system but also in the periphery and may aggregate in the intestines. Thus, we wanted to investigate how different environmental stimuli could affect the alpha-synuclein pathology, primarily in the gastrointestinal system. The microbiota composition and various infections can, for example, modify the local environment in the gut. I found this very intriguing to study as the microbiota and exposure to infections is something that concerns us all. The idea that our brain could be affected by conditions in the gut is fascinating.

What is the most important finding you have made during your thesis work?

We found that peptides from the bacteria Staphylococcus aureus speed up the pathological aggregation of α-synuclein in vitro. I think this is remarkable since this is a fairly common bacteria carried by 30–70% of the general population as a commensal bacterium.

Based on your findings, do you think that people have reasons to be afraid of this infection?

At this stage, definitely not! So far, we have only studied this outside the body. Our findings remain to be confirmed inside the human body, which will take time. For now, I would be much more concerned about getting infected by an antibiotic-resistant bacterium. That is a threat that is much more significant to society, and may cause serious complications.

Right now, there is a growing knowledge of how different bacterial and viral infections may affect the risk of developing other, non-infectious diseases in a longer perspective. But these risks are still very small, seen on a populational level. The reason we are interested in this is because a deeper understanding of these environmental triggers could help us identify genetic risk factors that are not yet studied. Maybe in the future, we will be better able to determine who is at risk of developing PD and then try to prevent it by screening for environmental triggers such as specific infections.

How did you end up at MultiPark?

At the time of my master's education, I came across Jia-Yi Li's studies since I was already interested in Parkinson's disease. We got in touch during the course in molecular neuroscience where he was a lecturer. Then I did my master's degree project in his lab, and that was how it all began.

What have you enjoyed the most during your research education at MultiPark?

Being in an environment where everybody knows each other facilitates collaborations with other research groups. Often, it does not even feel like a collaboration between groups, but more like an extension of your own team. And of course, I also have to mention the enjoyable retreats during the past, before the pandemic, when we could all meet in a relaxing venue to interact and discuss potential new collaborations and future projects.

What have been the most challenging aspects of your Ph.D.?

When experiments don't work out as expected. Inconclusive results are the worst! To me, it is not a catastrophe if my experiments yield unexpected results, which clearly reject my hypothesis, that is was science is about; updating our hypotheses in accordance with new data; sometimes you are right and sometimes not. But to get results that neither support nor contradict the hypothesis is challenging. And I think that this happens to most of us at some point. The only solution is to be persistent and do another round of experiments to find out if you did something wrong, explaining strange results in any of the previous trials.

Another tricky thing was to navigate in the jungle of protocols and methods that just appeared in my field overnight. The gut-brain axis is currently a hot topic and a lot of papers have been published over a short period of time. As the field was relatively new when I started, it was hard to judge which studies were of a decent quality. Since I mostly worked with the intestines, I had to adapt many protocols to that tissue.

The vogue for this research area also made it a bit into a race, where it is even more important to work fast and get publishable findings to avoid being scooped. This also makes it hard to choose your project because, as a Ph.D. student, you want to have a reasonably safe project to produce your papers in time for your defense. Still,  you don't want to spend time on too obvious questions with a high risk of not being unique in your contribution to the field.

And the most rewarding?

When I think of a question, I am actually paid to go into the lab and address my curiosity. We are all allowed to spend our working days digging into subjects we are interested in. How privileged is that!? And moreover, the working hours are highly flexible.

What do you like to do when you are not at work?

I love to hang out with my friends and drink beer, or any alcoholic beverages for that matter. Analog photography is another interest I have, and that started when I got an increased understanding of the mechanics behind the camera in the microscope.

What advice do you want to give to new Ph.D. students?

Many of us focus too much on how hard it is to pursue a Ph.D. It is, sometimes. But we tend to forget that other jobs can also be really frustrating. Maybe we could enjoy this time and getting to work in a creative environment with really smart colleagues!

Learning time management early on is a good investment. And to be very practical: be cautious with pouring Xylene into plastic containers (been there, done that!).

What happens after your defence?

If everything works out with traveling and getting the visa, I will hopefully move to New York and continue as a postdoc with my research on the gut-brain axis in Parkinson's disease.

More about Caroline Haikal's thesis

Caroline Haikal will defend her Ph.D. thesis titled “Alpha-synuclein: pathology, peripheral expression, and environmental interactions" in Segerfalksalen in Lund on 11 of March at 13:00.

Read more about the event in the calendar.

Follow the defence via zoom: https://lu-se.zoom.us/j/69226301112

Read the Ph.D. thesis "Alpha-synuclein: pathology, peripheral expression, and environmental interactions".