We’ve all grown up with our own favorite superheroes. Maybe you spent endless hours curled up with the comic books of Wonder Woman, or secretly imagined what it would be like to defy the city skies as Spider-Man. But even if you’re not familiar with superhero comic books, it’s hard to miss their adventures on the big screen these days.
In this series, Wtnschp is creating a ‘Marvel/DC Universe’ of its own. Like most superheroes, VUB scientists are just ordinary people using their smarts and talents to do good in the world. And just like Batman is inextricably linked to his Batmobile, or Iron Man to his high-tech suit, our researchers have their own supergadgets. With the help of FWO funding, 8 VUB research groups have acquired some new high-tech equipment that will blow your mind. First up is research group NAVI with their beloved ‘Seahorse’.
Our team is part of the research group Neuro-Aging & Viro-Immunotherapy or NAVI, at the faculty of Medicine and Pharmacy. Besides group leader Ann Massie, we have postdoc Gamze Ates, five PhD students and our technician Frank. And we’re always looking for new recruits … We all have one focus: xCT. That’s why we often call ourselves the ‘xCT team’! Our group has been studying xCT for almost 20 years and is still very exCiTed about it.
xCT is a protein that is present in our brain, in the cells of our immune system and on cancer cells. We showed that not having this protein is protective in mouse models for Parkinson’s disease and epilepsy. It can also be beneficial during aging. The latter observation is extremely relevant in an ever-aging society.
To understand why all this happens, we decided to have a deeper look at the ‘energy metabolism’ of cells when xCT is removed.
MEET SUPERVILLAIN xCT
Every cell has two engines that produce energy. Of course, these engines need fuel. A cell that can swiftly and efficiently switch from one engine or one fuel to another, is a cell that has the best chances to survive in changing conditions. Just like a hybrid car can switch to gas when it’s out of electricity, cells can switch fuel in case of fuel shortage or engine failure.
Brain cells need a lot of energy and when we age, cells have to deal with a scarcity of glucose, their most preferred fuel. If we can ensure that cells have sufficient alternative fuel sources and that they can successfully switch over to a different type of fuel, we can maybe promote healthy aging and prevent memory loss.
You could consider xCT as the ‘supervillain’ in this story since it removes glutamate – one of these alternative fuels – from our cells! That’s why we believe that shutting down xCT might be beneficial for our brain cells.
” Cells that can efficiently switch from one engine or fuel to another, have the best chances to survive. “
Our new supergadget, the Seahorse, will help us to investigate this. It measures the energy production in cells and gives an indication on the importance of the different engines in this process. It also allows us to study how efficiently a cell can keep producing energy when it promptly needs to switch from one fuel to another, or from one engine to another.
This is not only important in brain cells and during the aging process, but can also be important in cancer cells, immune cells that become activated, etc. After all, every cell needs energy to survive and dysfunctional engines are a common characteristic of many diseases. This is why the purchase of this equipment is supported by researchers working in the field of immunology, cancer, toxicology, aging, etc.
The Seahorse XFe96 analyzer (left) coupled to its sidekick, the Cytation 1 cell imager (right).
The full name of the brand-new equipment is the Seahorse XFe96 metabolic flux analyzer, and while it is not the only one in Belgium, it has the unique advantage of being coupled to a Cytation 1 live cell imager. The data that are generated by the Seahorse give us an idea of the total amount of energy that is produced in a sample, but it cannot take into account how many cells are present in that sample. This is where the cell imager comes in and automatically corrects for the number of living cells in the samples. That’s why the combination of the Seahorse and the cell imager gives high-quality, accurate measurements.
Energy production can be measured in 96 samples at the same time. This happens in real-time in living cells, while playing around with the fuel and blocking certain parts of each of the engines via automatic injection ports.
“Tthe combination of the Seahorse and the cell imager gives high-quality, accurate measurements. “
This is an example of what the Seahorse data can show. Here you can see the activity of two engines in the cell (the ‘red’ one, and the ‘blue’ one).
Let’s take a look at the scenario with the full lines, where both engines have enough fuel to work. After about 20 minutes, we started blocking the blue engine. You clearly see a drop in the blue line there, while the red one rises.
In short, when the blue engine is blocked, the activity of the red engine clearly picks up!
Thanks to its 96-well format, we can collect a huge amount of exCiTing data from a very small amount of sample. Another important superpower of the machine is the fact that it’s extremely user-friendly compared to other technologies that address ‘cell energetic’ questions. So, although it generates data in warp speed, you don’t have to be a rocket scientist to use it.
Would you like to know more?
Inspired by this story?
VUB researchers interested in acquiring scientific research infrastructure can contact the VUB Research and Grant Office (RGO@vub.be). They can assist you with your FWO application for medium-scale (150-1000k€) and large-scale (+1000k€) research infrastructure.
Article cartoon: © Wtnschp, by Alan Jockmans
Stock images: © Shutterstock
Photos seahorse & graph: © NAVI research group
About the author
Ann Massie obtained a master’s degree in Biology and a PhD in Science in 2003 at KULeuven. She next moved to VUB as a postdoctoral researcher, to become professor in 2011. Since 2014, she is leading the research group Neuro-Aging & Viro-Immunotherapy (NAVI). She has been studying glutamate transporters in the brain for more than 20 years and her team now focusses on one of these transporters: the cystine/glutamate antiporter system xc–.
About the author
Gamze Ates obtained a master’s degree in Drug Development in 2011 at VUB. In 2017, after obtaining her PhD in the field of Toxicology at VUB, she went to the Salk Institute for Biological Studies (San Diego, USA) to study brain aging and Alzheimer’s disease. She moved back to the VUB in 2020 as a post-doctoral researcher in the lab of Professor Ann Massie, where she studies the effects of system xc– in the aging brain and in Alzheimer’s disease.