Dr. Frederik Verweij is Assistant Professor at the Centre for Living Technologies, a part of the alliance of Eindhoven University of Technology, Wageningen University & Research, Utrecht University and University Medical Centre Utrecht. In the interview, he speaks about his research journey and two of his recently approved grant: VIDI and ERC Starting grants in 2022.
Tell us a little bit of yourself and your career path.
I started my PhD in 2009 in the lab of Dr. Pegtel in Amsterdam (NL) where I studied the sorting of a viral oncoprotein into exosomes as a way for the cell to cope with oncogenic signaling. Exosomes are a subpopulation of Extracellular Vesicles (EVs), very small lipid bilayer vesicles secreted by virtually every cell type in our body. In a healthy setting, these EVs, including exosomes, are implicated in communication between cells and organs in our body. We suspect they have a lot to do with how our body maintains homeostasis, remains stable in a changing external environment. During my PhD, I pioneered the visualization of exosome secretion from living cells by a TIRF live-imaging approach. Afterwards, in 2014, I started as a PostDoc at the Curie Institute in Paris (FR) in the labs of Dr. Raposo and Dr. Van Niel to study the physiology of endogenous exosomes in vivo by developing a novel zebrafish model system to study biogenesis, trafficking, target tissues and function of EVs. Since September 2021, I started as group leader in the division of Cell Biology, Neurobiology and Biophysics at Utrecht University.
Congratulations on your VIDI grant and ERC grants. Can you tell us more about the project? Are these projects related?
Thank you! Both projects focus on EV communication between different organs. In the VIDI project we will study how EVs from our intestinal epithelium (the gut) function under normal physiological conditions, and how pathologies, like cancer, affect this communication. The gut epithelium is normally very well organized (“polarized”). This means that the side that faces the inside of our gut, and the side that faces outward, i.e. the blood vessels that connect it to the rest of our body, are functionally different and also secrete different populations of EVs. Cancer disturbs this organization, and therefore likely also the EV-mediated communication of the gut with the rest of our body. We will investigate how this in turn affects cancer metastasis.
In the ERC Starting Grant project, we will focus on how EVs actually function. We want to investigate what type of “messages” these vesicles transfer and how they make sure that the right package reaches the right organ. We already have a lot of hints of how this works from previous studies, but the major drawback so far has been that we were only able to study these vesicles with indirect methods, out of their natural context. With this ERC, we want to “decode” these messages in their natural context, by using transparent zebrafish larvae. Here, we will focus on the liver, the central metabolic hub in our body that connects to all other major organs.
What are the possible applications of your research?
Both projects are fundamental by nature, but of course could have a variety of applications later on. With both projects, we hope to get a better understanding of how EVs function in health and pathology, and of course the most interesting follow-up question is how we can use that knowledge to fight diseases. We will focus on the mechanisms of EV secretion in vivo, and the next step will be to interfere with these processes in a very precise manner, either stimulating the release of beneficial EVs or blocking the release of pathological EVs. In other words, when we understand the communication lines and what goes wrong in a disease, we hope to be able to ‘rewire’ them.
What do you feel is the added value of interdisciplinary research?
At this point in history, there are many different research fields that are all highly specialized. This of course has greatly advanced a number of critical developments in each individual field. But as Karl Popper noted “We are not students of some subject matter, but students of problems. And problems may cut right across the borders of any subject matter or discipline.” That probably means that a lot of really interesting things will happen at the crossroads of interdisciplinary research. In our case we will implement developments from amongst others synthetic biology and biophysics.
How would this grant support the goals of the alliance?
One of the main focusses of this alliance is sustainability and preventive health. The content of EVs is strictly dictated by the cells and organs that secrete them. This means that if the cell changes, their EVs will change along with them. You could say that EVs are the tattletales of how our cells, tissues, and organs are “feeling”. Since these EVs can be easily isolated from for instance our blood, they can provide a wealth of information for prognostic and diagnostic purposes, in particular related to personalized medicine. The earlier we can detect diseases, the higher the better the treatment options usually are. Going one step further, one could also envision their use to identify at-risk populations for certain diseases. Better understanding of the basics of EV biology will greatly benefit all these potential applications.
What are your thoughts about writing a grant application? Do you have a process?
When I’m in the writing process,I don’t feel like I’m following a conscious process; actually, my mind is not that organized. But I do see it as some sort of puzzle. Usually, I begin by putting all possible thoughts down on paper. Then I start to think about the general synthesis, how everything fits together in such a way that there’s a logical progress in getting towards the overall goal. Ideally, I try to make each individual aim valuable on its own, in a way that it also adds more value to the other aims when accomplished successfully. To make all pieces fall into place can be quite frustrating, but it forces you to critically think about everything: the tools, the gaps in the field and the broad overview of what you want to do. And of course, during the whole process I discuss with other researchers inside and outside my particular field that can be really instrumental to find the key to solve the puzzle. All in all, I must say that the process in itself is already really rewarding, irrespective of whether you actually get the grant.
In your day-to-day work, what brings you joy and keeps you motivated? Briefly, what excites you about your work?
After all these years, I still love looking through the microscope, especially when looking at living zebrafish. You can see a beating heart, eyes, a blood circulation and so many other things. Life really is a miracle! Also, now that I supervise a lot of students, it feels like great joy to guide others in their own journey. And myself, I still learn every day!
What do you like to do when you aren’t working on research?
I like photography and enjoy listening to classical music/attending concerts.