Transposable elements in the healthy and diseased human brain

What have your Ph.D. studies focused on?

“During my Ph.D. studies, my focus has been analyzing sequencing data in relation to transposable elements. My research questions have explored different aspects of transposable elements, including their transcription and epigenetic regulation. 

This is important for the understanding of human brain evolution as well as diseases with complex networks where transposable elements may play a regulatory role. The expression of transposons in the human brain is a rising research field. Thanks to technological advances in recent decades, more researchers like us have been able to dig deeper into the role of transposable elements in disease contexts and answer big questions about evolution and brain development. 

In our lab, we are interested in studying the relationship between evolution and human disease, exploring everything from early brain development, including the evolution of the human brain itself, to the consequences of inflammatory states and different genetic disorders. During my Ph.D., my research has primarily focused on studying transposable elements in the human brain in various contexts such as development, healthy adulthood, and certain disease contexts. I have been mainly involved in the data analysis and interpretation of this data, working closely with biologists who conduct experiments in the lab. 

My focus has been on the data analysis side of things, employing different computational methods to deal with mapping ambiguity and adapting new technologies such as single-cell RNA sequencing to better understand three families of transposable elements. I have used various RNA and DNA-based technologies, including both short-read and long-read sequencing techniques, and worked to integrate these datasets, including bulk and single-cell datasets. Creating this bioinformatics pipeline has helped to make sense of the data collected as a whole, giving new insights into the human brain,” explains Raquel.

How did you end up doing a Ph.D. at Lund Stem Cell Center?

“I come from Mexico, originally from a town called Monterrey in Nuevo Leon, and moved with my family to Ensenada, Baja California on the West Coast at an early age. In high school, I was very much into physics; it was all about physics back then.

It was my interest in science that led me to pursue a bachelor’s degree in electrical engineering with a focus on computer science. During my studies, I had the opportunity to intern in biophysics, but my supervisor was mostly doing bioinformatics. That is how I was first exposed to bioinformatics and got hooked; I enjoyed the tangible applications that bioinformatics can have.

I applied to Lund University to pursue a master’s degree in bioinformatics and was fortunate to receive a scholarship during the 350th anniversary. While studying, I met my supervisor, Johan Jakobsson, who offered me a Ph.D. position in his lab (which is affiliated with Lund Stem Cell Center). 

Here in the lab, I have appreciated the opportunity to collaborate closely with the biologists. So, I do not know if I would have been a happy physicist if I had stayed on that path. I am quite happy that I ended up where I did,” reflects Raquel.  

Can you tell us about the cover of your thesis?

“You have to open the book fully. The background shows the sequences of the three families of human-specific transposons that we have been working with. The first is a LINE1 (L1HS), then an SVA F, and the last one is an LTR5-Hs.

I created this watercolor with the sequences of these transposons by assigning one color per letter and went with the first few hundred basepairs of each sequence. I digitalized the image and played with the colors a little so they would not come off too strong. After that, I asked my coworkers, friends, and some family members to draw the cells we used to investigate these transposons. So, here we have neurons, neural progenitor cells, and glial cells. I like that they were part of the process, I wanted each of us to represent the research we do. 

That is what it has been like for much of my Ph.D., abstracting ideas with people of different backgrounds and ways of thinking. I think it is a nice interpretation of how see our own research - that was the message behind it.  

At the same time, the background looks like a multiple-sequence alignment, which we often use for comparing sequences and tracing evolutionary origins from sequences. Or if you look at it another way, it also resembles a heat map, which we also use a bunch,” describes Raquel.

What have you found the most enjoyable during your Ph.D. studies? 

“My team. I have been very lucky with the people that I have met and worked with. I think that has been the single most important part of the Ph.D. for me, having a good work environment. 

The lab is very tight as a group, and everybody is happy to get new people in the mix. When I first arrived, there were so many incredibly sweet and kind people with bright and strong personalities, so it was a very welcoming environment from the start. It was so nice being around all these people who were so enthusiastic and passionate about science. I think that feeling is contagious when you have people like that around you every day.

Coming from a different background, I benefited so much from how open my colleagues were to talking, discussing, explaining, and answering all my questions. And I had a lot of questions. So, the fact that they were so open, so willing to explain and brainstorm – that was the most enjoyable part of the whole Ph.D.,” highlights Raquel.

What has been the most challenging aspect?

“My halftime. My halftime was a reality check. I had to make sense of a lot of things. I had produced a lot of results since my master's, but it was a lot to actually finish projects in order to publish. There was so much anticipation and suspense around it that by halftime I was starting to feel stressed, realizing that it was important to get projects done soon. So, it was a reality check that time was running out a little bit, but I also got questions that gave me a lot to think about. It was good, but it was challenging,” notes Raquel.

What are your plans following your Ph.D. defense?

“At some point during the Ph.D., I thought I wanted to move to industry, but now I think I might give academia another chance. I plan to continue with my research and see if academia calls me. For now, I am going to stay with the lab as a bioinformatician and finish some of the projects that I want to continue with. 

I am also going to start looking for postdocs. I have gotten some offers, but I have not taken anything yet. I do not want to jump without being sure about the focus and place. Specially knowing that I can stay here and finish the projects I already started, in an environment I like. So, I am taking my time to decide what comes next. 

I do know that I would like to stay in Sweden, though I am open to doing a postdoc somewhere else if it is a good opportunity. But Sweden has become home over the past six years, and I am quite established here now, so I hope to be able to stay in Sweden,” says Raquel.

Any other tips or advice for future Ph.D. students? 

“For future students, my main advice is to pick a good team. The most important aspect of the Ph.D. is to have a caring supervisor. If you do not have that, then you are done. Maybe that sounds a bit extreme, but it helps to have someone to look over your timeline and someone who believes in you, your potential, and your research questions. 

The second is to get collaborations, especially if you are going into bioinformatics. As a bioinformatician, it is key if you cannot produce your own data. When it comes to publications, it can be hard to get a first authorship, especially if you are not that into methods and more into data analysis. If this is the case, you may have to rely heavily on collaborations to get data. So, get going to those conferences, or make sure you have a great supervisor who can help set you up with collaborations within their network. 

My last point relates to the publication process, which is to remember that you can only do so much. You can only do your work and send your papers on time. After that, it is largely out of your hands, out of your control; you never know how long it will be in revision, for example. So, it is better to let go of the things out of your control and focus on what you can do - your work, your research. Easier to be said than done, but otherwise it can get quite overwhelming,” advises Raquel.

Anything else that you want to highlight about your time as a Ph.D. student? 

“There is something that I wrote about in the acknowledgments that I would like to mention. I came from electrical engineering/computer science, a field that is mostly male-dominated. I moved into this new environment mostly comprised of women. It was a big change having such a different dynamic and many women role models in the lab. It was very welcoming, as I mentioned, with so many very nice people, and I have found it very rewarding to change fields. I have never felt silenced, I have only ever felt empowered here,” concludes Raquel.