Reporter on the road: learning from microbes adapting to changing environments

18 March 2018
​They often say: “first love never dies.” Well, this might be true, at least for me.

August 2011. It is a warm Monday with sunny skies; it’s summer break. What more could a student want? Still a bit hungover from the night before, I take my bike and rush to the Bio-Incubator in Heverlee. I’m almost late on my first day. Together with some of my classmates, I officially kicked off my master’s thesis work in the lab of Kevin Verstrepen on that day. I would start pursuing my ultimate childhood dream: to study evolution. Yes, I was the geeky kid that read On the Origin of Species at the age of 13, and now, I could finally work on biology’s most beautiful theory myself.

Pretty much every genome is riddled with so-called ‘junk’ DNA, mostly consisting of tandem repeats, transposons and other funky DNA elements. But from an evolutionary point of view, this makes no
sense. Could there be some overlooked function to this so-called junk? In his previous work on yeast, Kevin had found that, indeed, such tandem repeats could be beneficial to an organism. I planned to follow up on this work and study how these repeats allow yeasts to adapt to changing environments.

Infectious excitement – I hoped
It was a tough year. We had – but we also wanted – to work hard and give it our best shot. I learned the ins and outs of yeast genetics, and of working with tandem repeats. I fell in love with what I was doing. I had never been so excited about anything in my entire life. This was what I wanted to do, period. In January of that year, I submitted my FWO proposal. I wanted to continue working with yeast through my PhD. The project was basic science, we had cool data, my grades were good: it was the perfect shot at a fellowship! How could anyone not be excited about this awesome project?

A small caveat: I really needed to get this grant. An applied grant at IWT would be not possible for such a fundamental project, and unfortunately, the PhD students before me had had bad luck with their applications and were being paid by the lab. There was no more budget left for me. It would mean getting a grant, or no PhD.

Moving forward, grant or no grant
Well, the review committee was clearly not as excited as me about the project proposal. My world collapsed. What now? After a few weeks of disillusion, I decided to make the best of it. Even though nothing would be as cool as what I was doing, I might find an interesting alternative. In applying to every neuroscience lab in Gasthuisberg, I was consistently told that all PhD positions were taken. But finally, against all odds, I was eventually able to squeeze into one lab. The year before scientists discovered that a tandem repeat expansion underlies most familial ALS cases, which was a breakthrough in the study of this dreadful disease. However, given that ALS was not considered a tandem repeat disorder before, ALS researchers generally knew quite little about these DNA elements. This is how I convinced Ludo Van Den Bosch and Wim Robberecht that my
expertise in yeast could, perhaps surprisingly, help them figure out how this tandem repeat causes the disease.

Falling in love all over again
Five years flew by. The experience I had gained in Kevin’s lab gave me an edge in this new and fast-evolving field. Together with collaborators at VIB and abroad, we were able to make some fascinating discoveries that opened up novel niches and illuminated the complex biophysics of protein aggregation in ALS. During my PhD, I ended up working with yeast, fly, zebrafish, mice and cell cultures. I jumped from genetic screening to
hardcore biophysics. I am sure I gave Ludo and Wim headaches from time to time with my endless list of “side projects” and “quick experiments”.

I never believed it could happen, but I was falling in love again. Yes, my heart still ached a bit at the thought of the project I’d left unfinished in Kevin’s lab. But here at Gasthuisberg, new doors had opened for me, as was the case in Brussels, Ghent and Antwerp through numerous collaborations within VIB. There was so much exciting stuff out there!

When life gives you lemons… do science!
I am a creature of habit. When I like something, I won’t easily change. Indeed, most Friday nights, I could usually be found among the same group of colleagues in the same bar, drinking the same beer, rocking out to the same 80s tunes. In science, I am pretty similar. When something grabs my interest, I won’t let go of it easily. But from time to time, one must change, broaden one’s horizons, etcetera. Good luck finding a position in science with expertise in only one specific thing! Science is becoming increasingly multidisciplinary, and it’s important to have that extra knowledge “baggage” to tackle complex questions.

In retrospect, not getting that grant wasn’t nearly as bad as I’d initially thought. It’s never fun to leave a project behind unfinished, but in return, I learned plenty of new and exciting things. When yeast is faced with a shortage in glucose, it will be disillusioned for a while, but it will eventually look around for other sugars to eat and new niches to conquer. My environment had also changed, forcing me to adapt, just like my beloved yeast cells. I learned to deal with rejection and made the best of my situation. Even though I continued to
focus on tandem repeats, switching to new model organisms gave me an entirely new toolkit and set of techniques that I might not have gained otherwise. More importantly, I realized that one closed door does not equal a dead end – just a detour. Passion for science will always find a way.

February 2017. It is a sunny winter day in California. I have just received a fellowship to continue my work on tandem repeats in ALS. However, I also picked up yeast work again, and labs from across the US are sending samples to fuel my side project on the evolution of repetitive protein sequences. First love never dies.

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Steven Boeynaems is a VIB alumnus who worked at the Kevin Verstrepen Lab and the Ludo Van Den Bosch Lab. Recently he traded Belgium for the Californian sun. At Stanford University he keeps pursuing his passion for science and science communication.

Twitter: @BoeynaemsSteven