VIB Times - 25 Years Anniversary Edition - December 2021

25 YEARS ANNIVERSARY EDITION DEC 2021

On the origin of impact Celebrating 25 years ground-breaking research at VIB

MAKING AN AMBITIOUS DREAM COME TRUE Jérôme Van Biervliet, Jo Bury & Ajit Shetty at the 25Y VIB celebrations

Twenty-five years ago, VIB began with the dream of building a life sciences powerhouse. Thanks to the biotech pioneers in Flanders at that time, we had all the raw material we needed: brains, ambition and vision.

The tight connection we have forged between science and valorization allows us to tackle global challenges. From pandemics to food production, VIB science strives to improve not only our lives today, but also tomorrow.

Since then, VIB has evolved into an institute that exceeds even our most optimistic expectations. The concept has not changed, though. The core of VIB’s success is our progress in scientific understanding. That's where we make the difference: the basic understanding of life. There is no progress, nor translation, without breakthrough science.

We will make that tomorrow as positive as possible with the help of the Flemish government, our tight partnership with the Flemish universities, fruitful collaborations with partners in and outside the biotech ecosystem, and of course the VIB community full of enthusiastic people. As we look ahead, we will continue to push the boundaries of science and technology while never losing sight of the people, inside and outside of VIB. We will break boundaries between disciplines and encourage collaborations in all sizes and shapes. We will reinvent ourselves as needed in order to create and sustain our impact on society, finding answers to the new challenges ahead of us. Continue what works, deepen where possible, and expand where needed; that is our vision for VIB’s future.

Translation – bringing breakthrough science to society – is VIB's second stronghold. It allows us to create impact on society. We invite you to discover some successes by diving into the origin stories in this special edition of VIBtimes.

What makes us unique as an institution is that we see no sharp boundary between basic research and translation.

Interdisciplinary teams within VIB create a stimulating environment that fits the needs of our scientists and builds bridges to translation. It is possible to dream big and make it happen.

The model of VIB – distributed but connected – has propelled us to the top of life sciences institutes in Europe and beyond.

As scientific experts with an entrepreneurial drive, we feed the ecosystem of biotech and life sciences companies in Flanders.

And in that future, we see VIB as a constellation of bright stars – emerging stars, growing stars and big stars. The magic happens when you connect the dots in the constellation. Via collaboration and imagination, a new and exciting journey awaits us.

So much incredible research, so many passionate individuals and teams. It is a privilege working with you. Thank you for celebrating with us, and for helping us build a bright future.

Jo Bury, Jérôme Van Biervliet & Ajit Shetty Managing directors and Chairman of the board of VIB

On the origin of impact

ON THE ORIGIN OF IMPACT

25 years of boundless curiosity have led to revolutionary discoveries and incredible societal progress.

Let us take you back to the very beginning, to the origin of impact.

THE DEVELOPMENT AND IMPACT OF NANOBODIES®

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From the early discovery of antibodies in camel blood to 5 VIB spinoffs and a multitude of applications.

UNRAVELING THE MYSTERIES OF ALZHEIMER'S DISEASE

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120 years after Alois Alzheimer's publication on his first case, the disease named after him is finally getting the attention it deserves.

HARNESSING THE MICROBIOME OF SOIL

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Using bacteria and fungi, VIB spin-offs Aphea.Bio and Protealis are developing new ways to stimulate plant growth and protect crops from disease.

ENABLING SCIENCE THROUGH TECHNOLOGY WITH VIB CORES

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Science and technology are deeply interconnected. Discover how the Core program facilitates excellent science by democratizing access to the cutting edge.

NEUROSCIENCE AND ELECTROENGINEERING

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Discover the origins of NERF, a global frontrunner in neuroscience combining biology with nanotechnology to create truly mindblowing exploration tools for the living brain.

BOOSTING OUR IMMUNE SYSTEM TO PERSONALIZE CANCER TREATMENT

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Advanced - single cell - research into immunotherapy could lead to personalized cancer treatments.

FIGHTING COVID-19: A STORY OF FLEXIBILITY AND COLLABORATION

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Groundbreaking basic research, extreme flexibility and intense collaborations. This is the origin story of our battle against COVID-19, to save the world from a global crisis.

VIB ALUMNI AWARD

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Rafael Van den Bergh receives the VIB alumni award for societal impact.

Explore more stories on vib.be/originofimpact

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The development and impact of Nanobodies®

HOW CAMEL BLOOD LEFTOVERS LED TO 5 VIB SPIN-OFFS Early 1990s. A scorching hot livestock market in Rabat, Morocco. A Belgian scientist named Serge Muyldermans is dealing with a local trader. Although Serge is clearly not in his natural habitat, he looks excited. The camel he just bought for 40,000 Belgian francs – now around 1,000 euros – could be the start of a promising new research avenue for him and the late VUB professor Raymond Hamers. Little do they know that they’re about to write one of the most successful international biotech stories ever.

Fast forward to 2021. More than three decades of research on camel and llama blood has resulted in multiple waves of impact.

Over the years, five VIB spin-offs have been founded, dozens of potential medicines have been developed, and the biggest biotech acquisition in Belgian history took place in 2018, when French pharma player Sanofi acquired Ablynx for 3.9 billion euros.

And the research is anything but finished. Since 1996, the VIB-VUB Center for Structural Biology, led by professor Jan Steyaert, has served as a hotbed for progress in this promising domain. And as we speak, new innovations in the fields of medicine, animal medicine and crop protection are being developed. All of them go back to a seemingly ordinary day in 1989.

On the origin of impact

Serendipity meets curiosity Another day at university in 1989. VUB biology students are everything but looking forward to their immunochemistry lab, where they have to detect and sort antibodies – substances that attack invading diseases – from animals such as mice, dogs, rabbits and birds. It’s an experiment with predictable outcomes: all antibodies are more or less similar. That is until professor Raymond Hamers suggests also testing dromedary blood because he happens to have some leftover blood samples in the freezer from an earlier research project on sleeping sickness.

When the professor reviews his students’ work, some of the results seem to be off. Perhaps the students simply misinterpreted the data. However, Hamers decides to look beyond the obvious explanation. When postdoc Serge Muyldermans comes to the exact same conclusions, both are stunned. Dromedary antibodies, and all camelid antibodies, in fact, seem to share a unique and simple structure – one that could offer huge potential for a wide variety of applications.

In the meantime, Raymond Hamers took steps to protect the invention. “The whole patent story was no walk in the park,” he said in previous interviews. “We even paid for it ourselves at an intellectual property office in Paris. Even more, we weren’t careful enough in terms of confidentiality and ownership of our invention. We ran into some issues, but many things changed after our first publication in Nature in 1993. Everybody gradually started to take us seriously.”

But in 1989, there was no VIB, no biotech ecosystem, no substantial financing and no professional tech transfer system to protect and further develop the invention. In other words, Hamers and Muyldermans were pretty much on their own.

Not only pharmaceutical companies reached out, but governments also started to show interest in what was going on in the labs. VIB was founded in 1995, and not a day too soon for this burgeoning new enterprise. Its dedicated Innovation & Business team is concerned exclusively with technology transfer

And that is how, a couple of years later, Serge Muyldermans found himself in a Moroccan market buying a camel to continue researching these particular antibodies, which were soon to be called "nanobodies".

and supports VIB scientists with valorization. Biologist Jan Steyaert came on board to further develop the technology and the business plan. “Finding investors was the trickiest part,” says professor Steyaert. “Investors tended to follow scientific hypes, which mainly featured synthetic antibodies at the time. We were those weird guys that suggested to immunize camels (laughs).”

Antibodies 2.0 Science can be a bumpy road, especially when you’re pioneering.

The first years came and went with ups and downs. But despite some setbacks in the lab and the mysterious disappearance of the Moroccan camel (probably stolen), the duo was able to further develop their findings. They managed to isolate one part of the camel antibodies, creating "single-chain antibodies" or "nanobodies".

It would take until 2001 for VIB to bring forth its first nanobodybased spin-off: Ablynx.

Serge Muyldermans and Jan Steyaert VIB-VUB Center for Structural Biology

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"Change only favors minds that are diligently looking and preparing for discovery" LOUIS PASTEUR

In Ablynx’s wake The launch of Ablynx was only the start of the nanobody success story. The long rocky road from origin to impact also served as a foundation to jumpstart new ventures. Under CEO Mark Vaeck, Ablynx started out with 10 employees and increased to 27 two years later. In 2006, the new CEO Edwin Moses took charge to guide crucial steps in the further evolution of the company. The pipeline was extended to 16 new substances with the potential to serve as foundations for new medicines. Ablynx continued to grow to approximately 500 people and expanded its patent portfolio, pharma collaborations and projects, which had domestic and international press regularly singing its praises as a company that put Flanders on the worldwide biotech map.

In 2018, Ablynx launched the first nanobody-based drug, caplacizumab, which treats aTTP, a rare blood clotting disorder.

The successes of Ablynx convinced French pharmaceutical player Sanofi to acquire the company in 2018 for 3.9 billion euros.

Bio-Accelerator housing Ablynx at Tech Lane in Zwijnaarde

On the origin of impact

Edwin Moses: “Three years after leaving Ablynx, I’m very proud to see that Sanofi continues to invest in the nanobody platform both in Ghent and around the world, with the aim to generate more new medicines based on this fantastic technology, and in addition, there are now about 10 former Ablynx employees who have become CEOs. It is fantastic to see this remarkable contribution of Ablynx to the local and international biotech scene.”

On top of Ablynx’s rise, VIB propelled new developments in nanobody research, resulting in the birth of four more spin-offs.

Biotalys (2013, formerly AgroSavfe) is using antibody technology to fight plant disease in agriculture. Confo Therapeutics (2015) is developing a new class of drugs and partnered up with Roche in 2017. ExeVir Bio (2020) is harnessing the technology to treat Covid-19. And for Animab (2020), the focus is to ensure the intestinal health of livestock. On top of this, other VIB start-ups like Orionis and Oncurious make use of nanobody technology.

VIB COMMEMORATES SCIENTIFIC CO-FOUNDER RAYMOND HAMERS FOR HIS LANDMARK CONTRIBUTIONS TO SCIENCE From nano to mega Parallel to the creation of new ventures, Jan Steyaert and his team at the VIB-VUB Center for Structural Biology are continuously taking the technology to the next level. In Flanders, the VIB Nanobody Core makes the antibody technology available to academic and industrial partners for a variety of applications.

Today, VIB has contributed to more than 400 nanobodyrelated peer-reviewed publications in high ranking journals, the establishment of several biotech companies, and of course new breakthroughs. For example, the last couple of years have seen new “Megabodies”, a novel kind of engineered nanobodies, being applied in cryo-electron microscopy to zoom in on the smallest proteins. Or "AcTakines", which combine mutant cytokines with nanobodies, and could be used in new treatment approaches for cancer and immune- or inflammation-related disorders.

And the founding fathers? They can be proud of what they achieved. The Nobel Prize in Chemistry Brian Kobilka and Robert Lefkowitz received in 2012 for the discovery of G proteincoupled receptors, based on the groundbreaking structural biology research at VIB, can be seen as the ultimate reward.

Looking back on the development of his brainchild, Jan Steyaert likes to phrase Louis Pasteur: "Change only favors minds that are diligently looking and preparing for discovery."

Raymond Hamers passed away on August 22nd 2021 at age 88 Hamers was a top scientist driven by curiosity and with a passion for training the young generation of future scientists. He had a very broad interest in biology covering the life cycle of parasites, understanding the immune defense of living organisms and unravelling the atomic structure of proteins and DNA. Jo Bury, Managing Director of VIB: “Raymond Hamers was a visionary and passionate scientist, and most inspiring person, who was by default a basic scientist driven by the quest for deeper scientific knowhow and insights. Even long after his retirement Raymond remained most active and engaged.”

VIB's nanobody-based spin-offs ablynx.com animab.com biotalys.com confotherapeutics.com exevir.com

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From genes to molecular mechanisms

UNRAVELING THE MYSTERIES OF ALZHEIMER'S DISEASE Back in 1901, German psychiatrist Alois Alzheimer described his first case of what later became known as Alzheimer's disease. Over a century later, we've learned a lot about the molecular processes that lead to neurodegeneration and subsequent memory loss, but many things are still to be discovered. As a result, an effective therapy hasn't been found yet. But the future is looking brighter. Two VIB group leaders who have been focusing on the hereditary form of the disease tell the long story of Alzheimer's research.

On the origin of impact

Christine Van Broeckhoven

Bart De Strooper

The hereditary form of Alzheimer's disease is rare. It usually starts at a young age, sometimes at thirty or forty years old. The majority of Alzheimer’s disease types, which are non-hereditary, are caused by a combination of ageing, environmental factors – such as obesity, diabetes, high blood pressure, lack of exercise, depression, smoking – and a series of genetic risk factors. Being a carrier of such a gene doesn't mean you'll develop the disease, but it does increase the risk. That's why Alzheimer’s disease occurs more frequently in some families, but not all family members will be affected.

find out how this disorder was passed on from generation to generation."

Chromosome 21

Van Broeckhoven investigated a Belgian family whose Alzheimer's disease appeared around the age of 35. "In this family, the transmission of the disease simply followed Mendel's laws of inheritance," says Van Broeckhoven. "But we didn't know which genetic defect caused the family's condition. What we did know, is that Down syndrome patients – who carry three copies of chromosome 21 – develop the same pathology as Alzheimer’s disease later in life. That drew our attention to chromosome 21 as the location for the genetic defect."

Talk about Alzheimer's disease, and you’re bound to mention Christine Van Broeckhoven. After starting up her own laboratory at the University of Antwerp in 1983, professor Van Broeckhoven was the first Belgian scientist to use recombinant DNA techniques, such as gene splicing and cloning. "In the 1980s, the first genetic maps of humans were constructed", says Van Broeckhoven, remembering her early career. "This allowed us to look at a complete family with a genetic disorder and

Van Broeckhoven's research group later discovered that a mutation in the gene coding for the amyloid precursor protein (APP) – located in chromosome 21 – is linked to early-onset Alzheimer's disease. The pathology involves so-called "amyloid plaques": protein aggregates that are associated with the development of more than 50 human diseases, with Alzheimer's disease being the most common.

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"Alzheimer's disease is finally getting the attention, research and funding it deserves."

Bart De Strooper VIB-KU Leuven Center for Brain & Disease Research

The egg of Columbus Professor Bart De Strooper has been focusing on the molecular mechanisms causing Alzheimer’s disease since the early 1990s.

"I entered this field of research at a pivotal moment," says De Strooper. "Building on the breakthroughs from the 1980s, some fellow researchers and I discovered that a second type of protein located on chromosome 14, known as presenilin, plays a crucial role in the development of Alzheimer's disease. This explained why, in some cases, the genetic problem was located on chromosome 14 and not on 21. Presenilins can be seen as "little scissors" that are supposed to cut the amyloid precursor protein in our brains. If this is not done in the right way, a short piece called amyloid-beta is released and starts sticking together, forming plaques.

"When we made this major discovery, I had just completed my PhD education. As a rookie in the scientific world, I still lacked experience. When Nature didn't accept the first version of my article on such an important breakthrough, I didn't understand.

But eventually, it dawned on me that I had to get rid of all old research data in the article and should focus only on the new findings."

In situ sequencing of plaqueinduced genes and cell type marker genes in a brain section of an Alzheimer mouse model

On the origin of impact

The article's second version was accepted and received as the egg of Columbus by the scientific world. The year after, in 1999, Nature published a second article by De Strooper about the role of presenilin in Alzheimer's disease. The following decades, both articles are highly cited, and the role and function of the molecular scissors is further untangled by De Strooper and his fellow scientists, including prof. Wim Annaert (whose lab identified an endogenous inhibitor that prevents gammasecretase complex assembly and activity) and prof. Lucía Chávez-Gutiérrez. These molecular scissors also play a role in numerous other cellular processes, and through a collaboration with VIB colleagues in the cancer field, insights from Alzheimer's also led to a new therapeutic approach for leukemia.

Cell by cell Following De Strooper's findings, it seemed like we were on our way to developing treatments, exactly one century after Alois Alzheimer's first identified case. But more than 20 years later, we're still waiting for the first effective therapy for Alzheimer's disease. De Strooper: "Practically all clinical trials up until now have failed, mainly due to strong side effects. The wrong patients have been targeted, the administered doses have been inadequate… Many reasons can be given for these failures. But I prefer to look ahead – and I'm very optimistic about the future.”

"By using the latest technologies at single-cell level, we managed to integrate the disparate knowledge in a comprehensive and coherent picture of the cellular processes at the root of Alzheimer's disease, involving not only neurons but also astrocytes and microglia. Renzo Mancuso (group leader at the VIB-UAntwerp Center for Molecular Neurology) studies the role of the neuroinflammatory processes in the brain governed by these cells. With this level of detail, we can get a much more fine-grained picture of how different patients are affected by the disease process. This means more specific trials can be run, and the first results are promising. For the very first time, we have clinical proof that a drug is removing amyloid plaques.”

Breaking the taboo "I can't guarantee our latest efforts will lead to the development of an effective treatment, but the gates are wide open for more clinical trials. I'm happy to see that Alzheimer's disease is finally getting the attention, research and funding it deserves – which is reflected in the launch of the VIB spin-off Muna Therapeutics, for instance. Following cancer in the seventies and AIDS in the eighties, the taboo around Alzheimer's is finally being broken as well."

Alzheimer's is the most common, but not the only type of dementia. Rosa Rademakers, who recently took over the baton from Van Broeckhoven as director of VIB's Antwerp research center is an authority when it comes to the genetics of frontotemporal dementia. Like Rademakers, many more group leaders and junior scientists have joined the mission to defeat dementia since Van Broeckhoven and De Strooper's seminal work.

"I'm glad to see a lot of young scientists are involved in neuroscience," Van Broeckhoven adds to that. "These engaged people are crucial for the future of research into a complex disorder revealing more and more of its secrets each day. About time, I'd say."

"I'm glad to see a lot of young scientists are involved in neuroscience."

Christine Van Broeckhoven VIB-UAntwerp Center for Molecular Neurology

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Harnessing the microbiome of soil

SUSTAINABLE AGRICULTURE USING BACTERIA AND FUNGI The soil in which we grow our crops contains billions of bacteria, fungi and other microorganisms that are more powerful than you might think. These can devastate our plants – think back to the potato blight that led to the Great Famine – but they also possess the power to strengthen crops, making them more resistant and faster growing. Enter VIB. Even back in the 80s, researchers worldwide were already gaining insights into growth-stimulating microorganisms. But this field of research has truly flourished only in the past few years, right here in Belgium. Recent technological breakthroughs and tech transfer efforts have led to the foundation of Aphea.Bio and Protealis, two VIB spin-offs that are exploring and developing a new generation of agricultural solutions.

On the origin of impact

From human to plant Any idea what happens when experts in microbiology and plant science meet? A cross-fertilization that exemplifies the strength of VIB. The main goal of scientist Jeroen Raes, group leader at the VIB-KU Leuven Center for Microbiology, has always been to better understand the relation between the gut microbiome and human diseases, such as cancer and autoimmune diseases. But recently, the impact of his research has become much broader.

He teamed up with Sofie Goormachtig, group leader at the VIBUGent Center for Plant Systems Biology.

Jan Michiels, group leader at the VIB-KU Leuven Center for Microbiology followed a similar research path: "People suffering from chronic and recurrent infections often harbor pathogenic bacteria with high antibiotic tolerance. We are investigating the mechanisms that help these extremely stress-resistant pathogens to survive antibiotic treatment in order to develop better antibiotics that can kill them. Our findings in the human microbiome help us to do exactly the opposite when it comes to the plant microbiome: we develop highly stress-resistant beneficial bacteria that fix atmospheric nitrogen for the plant.

Usually, more than 90% of the bacteria that we apply to seeds die immediately after planting. But if we manage to make these bacteria more stress-resistant, more will be able to survive the harsh conditions and fix nitrogen to the benefit of the plant."

Idealism and curiosity One of the VIB spin-offs relying on this groundwork is Aphea.

Bio. The Ghent-based company focusing on next-gen agrobiologicals is growing very fast, working closely together with Sofie Goormachtig. She is investigating how plant roots interact with neighbouring organisms in our soil. "With the help of VIB's Innovation & Business team, we developed the proof of concept for Aphea.Bio, contributed to the business plan and provided scientific advice," says Goormachtig. "That may seem like a huge stretch for scientists who focus on basic research, but the opposite is true. When starting a VIB spin-off, you’re always surrounded by professionals with complementary skills. In this case, I was happy to see CEO Isabel Vercauteren and CSO Steven Vandenabeele take on the management responsibilities."

Bringing in his experience as research manager at BASF CropDesign, Dr. Vandenabeele joined the team in 2015. "It was my job to build a business case," says the Aphea.Bio CSO. "I examined potential crops, explored the market, mapped out farmers’ demands, etc. Aside from that, I was charged with guiding the proof of concept in order to support this case. In my experience, that was one of this journey’s most challenging endeavors. The second one was fundraising, but that’s where Isabel came in.”

Dr. Vercauteren: “I was R&D licensing and new ventures manager at Bayer CropScience when Sofie and Steven asked me to join their promising project. My first big task, raising the necessary funds, was both challenging and exciting. Our very first pitch hit a few speedbumps, but we soon grew into our roles, finetuned our presentation and learned how to tick all the boxes from an investor’s perspective.

“In the end, we successfully raised EUR 9 million in our first investment round and received the support of Flanders Innovation & Entrepreneurship (VLAIO). A few years later, in 2020, we entered a new phase of fundraising to market the products we developed. The equity investment of the European Circular Bioeconomy Fund (ECBF) brought our capital injection to a total of EUR 18 million. We're now ready to advance our product portfolio towards regulatory approval and a first commercial launch."

Jeroen Raes and Jan Michiels VIB-KU Leuven Center for Microbiology

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Focusing on applications in nutrient stress and diseases, Aphea.

Bio's business plan differs slightly from what Sofie and her team originally had in mind. "Basic science and business are two sides of the same coin," acknowledges Goormachtig. "This is especially true at VIB, because we strongly focus on the translational value of research. Scientists tend to be idealistic about the potential applications of their findings, but I still believe that idealism and curiosity are indispensable forces required to push boundaries and generate real societal impact. It’s our job to ask fundamental questions, even if it will take decades to translate the answers into applications."

The power of soybeans Reducing fertilizer application and controlling fungal diseases sustainably in maize and wheat, Aphea.Bio is not the only spin-off relying on VIB's earlier research to pioneer in the field of sustainable agriculture. Founded in April 2021, Protealis aims to harvest the full potential of legume crops, inspired by the mission to locally grow more sustainable plant-based proteins. The initial focus is to develop high-yield, high-protein soybean varieties using plant growth-promoting bacteria.

These innovations build on the work of the VIB labs of Sofie Goormachtig and Jan Michiels, and the ILVO (Flanders Research Institute for Agriculture, Fisheries and Food )teams of Joke Pannecoucque and Isabel Roldán-Ruiz.

“Legume crops are excellent sources of protein and can be grown sustainably, as they do not require nitrogen fertilization," says Protealis CEO Dr. Benjamin Laga. "With their soil-improving characteristics, legumes are an excellent addition for farmers in crop rotation. Soy, containing up to 46 grams of protein per 100 grams of beans, is a logical first choice of crop for Protealis."

ILVO played an important role in the foundation of Protealis.

VIB and ILVO have been collaborating since 2016, combining expertise in basic research (VIB) and applied research and

fieldwork (ILVO) to study the results in more depth. Thanks to this joining of forces, scientific discoveries can be translated faster into tangible added value for farmers, society and the environment. In this case, Protealis relies on research into yield-enhancing soil bacteria by VIB and breeding technologies developed by ILVO.

The power of people Another result from the fruitful collaboration between VIB and ILVO is "Soy in 1000 Gardens", a citizen-driven science project that aims to introduce soy as a crop in Flanders. In early 2021, more than a thousand citizens were recruited to grow and analyze soy in their own gardens and fields and respond to surveys about its progress. In the summer, their plants were collected for research.

"In a first phase, we want to investigate where beneficial bacteria that enhance the growth of soy are already present in our soil," Dr. Lena Vlaminck, who manages the scientific part of this project, explains. "Later, we want to develop guidelines and applications to boost the yield of soy cultivation in a sustainable way. At the moment, Belgium imports approximately 800,000 tons of soy annually, mainly from South America. Local soy production on a larger scale would also benefit our ecological footprint."

Learn more aphea.bio protealis.com soyin1000gardens.be

Farmer-scientist Joe Dieryck, Isabel Roldan-Ruiz (ILVO) and Sofie Goormachtig discuss the Soy in 1000 gardens citizen-science project at 25Y VIB

On the origin of impact

"Idealism and curiosity are indispensable forces required to push boundaries and generate real societal impact."

Sofie Goormachtig VIB-UGent Center for Plant Systems Biology

Part of the Soy in 1000 gardens team at VIB-UGent Center for Plant Systems Biology

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Enabling science through technology with VIB Cores

HOW TECHNOLOGY IS ACCELERATING SCIENCE: MEET THE VIB CORES “It’s impossible to arrive at groundbreaking discoveries without access to the cutting edge," says Dr. Geert Van Minnebruggen, head of the Science & Technology Unit at VIB. But the cutting edge doesn’t come easily, cheaply, or simply. Over a decade ago, VIB embarked on an audacious mission: to ensure that a steady, well-founded, validated supply of high-impact technological tools is accessible not only for our own.

2000 marked the birth of VIB’s very first core, The Micro Array Facility, launched to offer VIB research groups centralized technology platforms with economies of scale.

“VIB prioritizes the availability of high-performing, state-of-the-art infrastructure that covers all life sciences disciplines, from disease pathways to genome insights,” explains Van Minnebruggen. “The Core program has robust, highly developed tech that it offers to VIB researchers as well as external scientists, groups and companies – for a fee.”

On the origin of impact

Van Minnebruggen: “Core Facilities play a crucial role for the entire life sciences network. They make sure that scientists – internal and external – can do top-level research in a costeffective way. Over the years, the program at VIB has expanded to include additional domains, new technology platforms and the involvement of VIB and university campuses in Ghent, Leuven, Brussels and Antwerp.”

"Competitors can be powerful collaborators. Through Core for Life, VIB scientists can team up with other European core facilities."

“The result is one of Europe’s richest, strongest, most powerful ecosystems not just of science enablement through proven

Geert Van Minnebruggen Head VIB Core Facilities

Ecosystem throughout Flanders Pharma and biotech companies have to keep up with new technological evolutions, but most companies don’t have the time or expertise needed to implement them. VIB Cores offer these services and also allow companies to access new technologies. In turn, external partners help finance Core infrastructure and cut costs per experiment.

tech, but of information exchange, training and expertise,” asserts Ivan Baines, chair of the international expert committee responsible for evaluating the Core program at VIB.

One platform to rule them all “After working for 15 years in research, I joined the Bioimaging Core back in 2011,” recalls Saskia Lippens, now head of the Bioimaging Core in Ghent. “I’ve seen huge growth over the last ten years – new facilities joined and individually expanded their portfolios as well. But the most important evolution taking place was the interconnections forming between core facilities at VIB. While the technologies used can be very different between cores and require completely different expertise, Geert managed to bring us all together.”

In Lippens’ view, this was a flipping point for the program. “Peer coaching was the natural next step once we started working more closely together because even across domains, we often face similar challenges,” she asserts. “Another outcome was greater visibility of the many technologies available at VIB – we even market for each other. The biggest advantage here is that researchers can tap into a complete program involving several core facilities that all work in a similar way.”

Geert Van Minnebruggen and Saskia Lippens at 25Y VIB

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Opening the doors to Europe The next big leap happened in 2013 with the Core for Life initiative: an alliance between VIB and five European life sciences research centers driven forward by Geert Van Minnebruggen and Doris Meder from the Center for Genomic Regulation (CRG) in Spain.

of interest to the VIB community. The Technology Innovation Lab often works alongside Core facilities to help evaluate and optimize these tools. A selection of these tools that prove to be robust, are incorporated into the Core Facilities technology suites and are subsequently offered to the VIB community as part of routine service.

“We knew firsthand how expensive and knowledge-intensive it is to train and retrain staff to keep up with "tech turnover" – the replacement of old tech with the next generation,” Van Minnebruggen goes on to say. “Handling all of this training in the walls of a single institute is almost infeasible.

“Since 2017, the Innovation Lab has linked VIB Cores with Tech Watch innovations and ensures that the tech and the literacy are refined as effectively as possible,” Novak goes on to say. “The 10xGenomics single-cell sequencing platform is a great example of the Innovation Lab’s work in action.”

“Competitors can be powerful collaborators, and plenty of other

The invaluable role of facilitator

life sciences institutes in the EU have core facility programs.

Through Core for Life, VIB scientists can team up with those at other European core facilities, and gain access to another eight core programs at top institutes. We can send our people to environments where new platforms are already in place – accelerating that learning curve – and it happens in both directions.”

Core facility programs aren’t uncommon around the world. “But VIB is absolutely one of the institutes in Europe that serves as an exemplar for others – we’re at the forefront,” Lippens asserts. “It was clear to us from quite early on that the VIB Core program needed to add value far beyond simply access to technology. We have a strong focus on expertise, with 80 highly skilled people working at VIB Cores."

The trinity of tech translation

“There is also huge potential here when it comes to career trajectory. You can be a scientist in many ways; it’s not mandatory to be a basic researcher working on highly specific biological questions. It’s really rewarding to be a tech expert and facilitate the work of other scientists as an enabler.”

In addition to the Core program, VIB has two other vital initiatives in place that complete the entire cycle of tech discovery, development and dedicated use in research: Tech Watch and Innovation Lab. “Tech Watch has been running at VIB since 2008,” says Dr. Halina Novak, Technology and Innovation Program manager at VIB. “It’s the vehicle we rely on to scout for new technologies before or just after they reach the market and bring them into the VIB environment – an initiative that has been extremely successful.”

But bringing in the most promising innovations is only the very first part of the puzzle. After all, undeveloped, unproven tech, no matter how promising, poses plenty of challenges before it can be refined to the point where it is useful in scientific research.

“Early technology can be so fragile, and Cores need very robust, reliable, consistent platforms in order to deliver groundbreaking results,” Van Minnebruggen explains.

This is precisely where the third piece of the puzzle fits in: the Technology Innovation Lab. Here, specialized scientists investigate the technologies identified by Tech Watch which are

Halina Novak VIB Tech Watch

On the origin of impact

"I do love research, but my current role allows me to dedicate my expertise and contribute to answering a broad range of scientific questions."

Saskia Lippens VIB Bioimaging Core Ghent

Lippens deeply values this possibility in her own work as the head of the VIB Bioimaging Core Ghent. “I do love research, but my current role allows me to dedicate my expertise and contribute to answering a broad range of scientific questions.

“We might switch disciplines if outsourcing is more cost-effective or if a vital new tech emerges, for example,” Van Minnebruggen explains. “Because we expect future technologies to demand more and more expertise in multiple fields, we will focus more

Rule number one in the Core program is teamwork. We must all function smoothly together in order to add the tremendous value that comes when you successfully align many different technologies to respond to a basic question. My colleagues and I touch so many different biological ideas every single day.”

on bringing knowledge from our Cores in an integrated way.”

Change as the only constant The search for new technology – and its development – is never over, and VIB Core facilities aren’t written in stone, as the Cores that exist today don’t cover the same disciplines as they did just a few years ago. Current VIB Cores are known for their single-cell capabilities since research in this field requires diverse expertise and the ability to collaborate very closely.

On that note, the VIB Cores are evaluated by an external panel of international experts every five years, offering advice and guidance on the program’s roadmap and development. “This evaluation is really important to us because it challenges us to proactively shape our leading role in the global biotechnology ecosystem,” Van Minnebruggen concludes. In November 2019, the on-site visit took place and the cores received high praise – and future-focused recommendations – from an international, interdisciplinary panel of technology experts. The review concluded that VIB’s core program is operating at the very highest level and is recognized as a gold standard in Europe for how core facilities should be implemented and operated.

CORE FACILITIES

TECH WATCH

INNOVATION LAB

VIB has 10 institutional Core Facilities in total, providing support in a wide array of research fields and housing specialized scientific equipment and services for each discipline.

Tech Watch spots, evaluates and implements breakthrough technologies to push VIB’s innovative research to the next level. Funding and hands-on support allows us to engage in high-gain high-risk technology projects with early-access technology.

The Technology Innovation Lab is rolled out to facilitate the in-house adoption of pre-commercial or recently commercialized instruments, offering a bridge between external early-access prototypes and commercial walk-away instruments.

connect.vib.be

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Neuroscience and electroengineering

NERF: WHERE CUTTINGEDGE NANOTECHNOLOGY AND NEUROPHYSIOLOGY UNITE Hot on the heels of VIB's molecular neuroscience research, VIB managing director Jo Bury and imec director Gilbert Declerck invited the brightest minds in Flanders from both VIB and imec to come up with the next big idea in exploring the functioning of the brain. “We put them together in a board room for two brainstorming sessions and - by manner of speaking - didn’t let them out until they came up with something really crazy,” Bury recalls with a broad smile. “You wouldn’t believe how quickly they emerged.” On that day in 2008 the earliest beginnings of Neuro Electronics Research Flanders, or NERF, were firmly taking root.

It’s not that NERF started in a garage – but the big dream vibe was definitely there. “The whole concept began when Gilbert Declerck, at the time director of the micro- and nanotechnology research institute imec, and I got together and started talking 12 years ago,” says Jo Bury, managing director of VIB. “We were both leading strategic research centers in Flanders, but in completely different areas – VIB in life sciences, imec in micro-electronics. We both shared this starry-eyed ambition of fusing the state of the art in biology with the cutting edge in micro and nanotech.”

On the origin of impact

Intriguing concept, but a bit too broad. Their discussion got more and more detailed as they reflected on which fields in biological sciences would be transformed most dramatically by electronics.

“Of course, that’s when we arrived at the brain and the nervous system, a complex network of pathways for electrical signals in the body,” Bury continues. “Neuroscientists at VIB were already growing brain cells in the laboratory, and we wondered, ‘can we grow actual neuronal circuits in vitro and measure their electrical activity in real time?’ It really fired us up.”

All fired up VIB scientists and imec engineers put their heads together and came up with a way of growing neurons in a grid array aligned with sensors that measured their activity. “Which was very cool to see,” Bury adds. “But it was kind of artificial and did not lead to a better understanding of a functioning brain. The team needed to work in vivo – studying live animals – to measure real, functioning circuits in the brain. The question was how.”

The VIB/imec team wrote a vision text on electrophysiology in vivo and performed a desk study to investigate what tech was already out there for brain imaging, and what relevant research scientists had already been done. Bury: “We identified an exciting niche and explored whether our vision was doable, realistic, and timely (not too early, nor too late). The benchmark study revealed the existence of many evolving paths in electrophysiology, but nothing along the lines we were thinking: developing new micro-electronics and nanotechnology tools to measure brain activity at high resolution (thousands of neurons simultaneously) in live, awake, behaving animals, to study neuronal circuits in the brain, trying to understand how sensory input to the brain is translated in memory building and output, in terms of activity or behavior.”

Growing a network The first thing to do was to get the start-up money together to turn this moonshot into practice. We estimated we would need at least 20 M€ to launch the initiative and bring it to maturity.

To do so, we joined forces with three founding institutions: imec, KU Leuven and VIB. The initiative received support from the Flemish government as well. The next step was to set up a systems neuroscience lab where we could attract top international scientists in the field,” Bury explains. “Our very first principal investigator at NERF was Emre Yaksi, a promising scientist from MIT, working on the olfactory system in zebrafish; the start of an exciting but bumpy road.”

Bury: “We were very fortunate that truly world leaders in this field were excited and inspired by our vision and became members of the international scientific advisory board of NERF, to help us in recruiting the right scientists and develop the scientific plans and focus of NERF. The Scientific Advisory Board experienced the ambitious set up of NERF as the well-known Bell-labs set up of AT&T (now Alcatel-Lucent) in the early 194050s.”

The multidisciplinary team began by studying brain inputs – vision, hearing, smell, taste and touch – to investigate what responses these inputs caused on the level of the entire system, which involves multiple neurons interacting and creating outputs in the form of memories and reactions.

Bridging genetics, neurobiology and nanotechnology This three-party, double-faceted approach combining neurobiology and nanotechnology immediately proved its worth – and its distinctiveness. “NERF is unique in this regard,” asserts Sebastian Haesler, current director of the research center. “The formula works: the technology we develop here is used by systems neuroscientists all over the world.”

"The formula works: the technology we develop here is used by neuroscientists all over the world."

Sebastian Haesler NERF

Two other VIB research centers are deeply involved in the basic research required to support NERF’s ambitions. The VIB-UAntwerp Center for Molecular Neurology focuses on neurodegeneration and human genetics, with researchers investigating the genetic mutations behind neurodegenerative diseases. The VIB-KU Leuven Center for Brain & Disease Research is concerned with the next step: the cellular and molecular mechanisms that physically cause diseases.

“NERF is the third step, bridging the domains of neurobiology and nanotechnology in order to more deeply understand how neurons function in the human brain,” Haesler adds.

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New technologies, one after the other Today NERF houses six research groups with scientists of diverse backgrounds: bio-engineers, geneticists, neurobiologists, physicists, mathematicians… All groups are headed by leading scientists, recruited internationally from Harvard, MIT, FMI, Max Planck, etc. Principal investigators at NERF have been responsible for several key breakthroughs over the years, leading to the institute’s worldwide reputation as a cutting-edge neuroscience player.

Neuropixels 2.0 (c) imec

“One of these breakthroughs lies in research spearheaded by Karl Farrow aiming to uncover the interconnections between different neurons, such as those in the eyes, which detect light and dark, and those in the brain responsible for translating those signals into images that we can interpret,” says Haesler.

“Our scientists discovered completely new circuits in this regard, publishing their results in Neuron, the top journal in the field.”

Led by Alan Urban, NERF researchers also developed ultrasound approaches for the brain, unlocking the ability to measure brain activity based on blood flow. This technology could be particularly useful in detecting low oxygen levels and potential brain damage in neonates, whose skull bones haven’t completely fused together.

Measuring brain activity in 6,000 locations at once The latest news out of NERF making big headlines? “That would have to be Neuropixels,” Haesler immediately responds.

Developed by imec, in collaboration with NERF and an international consortium of partners and collaborators, Neuropixels are tiny electrodes – thousands can fit on the end of a probe as thin as a hair – that can measure the activity of thousands of neurons in a single living brain simultaneously.

Jo Bory and Sebastian Haesler VIB Managing director and NERF director

On the origin of impact

“This activity can be recorded over longer periods of time – not just to expand our understanding of brain processes like learning and memory, but also of brain diseases,” Haesler explains. “NERF worked with five large international institutes to develop Neuropixels 2.0, which are three times smaller and capable of recording electrical activity in 6,000 brain locations simultaneously on a long-term basis. Thanks to these developments, scientists from across the globe can study the brain in unprecedented richness and detail.”

Trials and tribulations, back and ahead From today’s vantage point, the history of NERF seems starred with success stories. “But getting the ball rolling and keeping it going was really tough work,” Bury reflects. “There were many

unused to working with living organisms, to combining completely different cultures. But we adapted and created a new environment, completely from scratch. I have to say I’m very proud of how far we have come together.”

Bury hasn’t lost his “dream big” attitude, however, and Haesler is on the same page. “So, now we can accurately measure and record the activity of thousands of neurons in a living brain. But here’s a wild idea: what about individually measuring the activity occurring in the different synapses of a single neuron at once?”

Bury wonders. “Or,” adds Haesler, “what about investigating the molecular biology and genetics behind the formation and functioning of our nervous systems – is this environmentally driven or built into our DNA? We still have so many questions!”

hurdles in our path, from introducing biology to an organization

Spinal cord section with motorneurons stained in green, excitatory interneurons in purple and an activity marker in yellow

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BOOSTING OUR IMMUNE SYSTEM TO PERSONALIZE CANCER TREATMENT Immunotherapy only broke through about a decade ago but has already won a Noble Prize. This revolutionary way of treating cancer boosts the patient's immune system to destroy cancer cells. The problem is that, while this could save the life of some patients, others may be resistant to the therapy and suffer from the sideeffects and high costs without reaping the benefits. By investigating the response to immunotherapy on the single-cell level, aided by advanced technology and a large number of patients, researchers at the VIB-KU Leuven Center for Cancer Biology are paving the way for more personalized cancer treatment.

On the origin of impact

Cancer comprises a multitude of different diseases, and every patient reacts differently to frequently used therapeutic approaches, such as radiation and chemotherapy. In the late 19th and the early 20th century, the first attempts in the Western world were made to infect patients with weakened bacteria or viruses to activate their natural defense mechanism, aka the immune system.

The results were not overwhelming, but scientists still believed that triggering the immune system might be a successful strategy to fight cancer and kept engaging in basic research into immunity regulation.

The rise of immunotherapy In 2018, James P. Allison and Tasuku Honjo jointly received the Nobel Prize in Physiology or Medicine. Allison and Honjo each examined a different protein and found that both work as a "brake" on the immune system. The act of releasing that brake, unleashing our immune cells to attack tumors, is what became known as immune-checkpoint blockade (ICB), the mechanism behind a type of immunotherapy called immune-checkpoint blockage therapy.

Remarkable scientific progress has been made since then, but that

Over the past few years, the potential of ICB therapy has been investigated through hundreds of clinical studies in multiple cancer

has rarely led to generally applicable cancer treatments. However, a change is on the horizon… "When it works, immunotherapy is truly amazing," says Diether Lambrechts, group leader at the VIBKU Leuven Center for Cancer Biology.

types. In many cases, the clinical trials showed encouraging positive effects. However, the results were also extremely variable and unpredictable, while resistance, relapse, and side-effects were common.

The recent developments in single-cell technology have been a major catalyst in understanding why some people respond positively to ICB and others don't. By using such technology, enabling in-depth studies of individual living cells, VIB is able to analyze samples of the tumor and its microenvironment at single-cell level. That way, detailed single-cell maps of the tumor microenvironment before and during ICB therapy can be compared to investigate which biomarkers – measurable indicators of pathogenic processes, in this case the dynamic interactions between cancer and immune cells in the tumor microenvironment – can predict the outcome of the therapy.

"Immunotherapy is a real gamechanger.

For some people, it means the difference between life and death."

Diether Lambrechts VIB-KU Leuven Center for Cancer Biology

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Setting up fine-grained single-cell maps

Breaking therapy resistance

To accelerate progress in this emerging field of cancer treatment, VIB started the Pointillism research track within the Grand Challenges Program in 2018. "Immunotherapy is a real gamechanger," states Diether Lambrechts, who's in charge of the research track. "For some people, it means the difference between life and death, as simple as that. That's why we want to gain as many insights as possible, as soon as possible. Our main goal is to predict which patients will respond to the therapy and which won't, before immunotherapy starts. For those who won't respond, we want to use that information to develop different treatments that can extend their lifespan in a qualitative way."

Jean-Christophe Marine, group leader at the VIB-KU Leuven Center for Cancer Biology, co-leads the Pointillism project and has been focusing on melanoma, a type of skin cancer. For a long time, it was widely accepted that resistance to melanoma therapies was caused exclusively by genetic alterations – mutations – in the cancer cells.

However, recent research suggested that the resistance can also arise via non-genetic mechanisms that change the expression of certain genes without altering their DNA sequence. How and why the genetic or non-genetic route prevails remained unclear, but a recent publication in Cancer Cell has lifted a corner of the veil.

In the Pointillism project, immunotherapy trials have been selected in four different cancer types, to assemble a comprehensive collection of pre- and on-treatment biopsies from patients.

Lambrechts: "Since breast cancer is the most common cancer type we're investigating, that particular trial delivered the first results. In collaboration with the Multidisciplinary Breast Center of UZ Leuven, we used single-cell technology to study the tumor microenvironment of 40 early breast cancer patients treated with immunotherapy. This is the first time such a large cohort of breast cancer patients has been analyzed on the single-cell level."

"The results show clear differences between patients predicted to respond to the therapy, so-called responders, and the nonresponders. The clear but subtle differences wouldn't be noticed with other approaches. Studying the differences between both groups allowed us to define a surrogate marker for response based on specific characteristics of the tumor and its microenvironment.

This shows that our fine-grained single-cell maps of the changes in the tumor microenvironment during treatment yield results."

Diether Lambrechts and Chris Marine VIB-KU Leuven Center for Cancer Biology

On the origin of impact

"We showed that resistance to melanoma therapies is not random, but predetermined," professor Marine explains. "The presence of a specific cell type, neural crest stem cells, leads to non-genetic rather than genetic therapy resistance. These stem cells can literally "reprogram" themselves to evade therapeutic pressure.

We managed to go a step further and identified the protein that promotes the emergence and survival of these stem cells. By blocking the activity of this protein, we were able to drastically reduce non-genetic drug resistance in patient-derived tumor cells that were implanted in mice."

"These findings have important clinical implications," adds senior postdoctoral fellow Florian Rambow, who was involved in the study. "Not only did we show a viable way to suppress non-genetic resistance to melanoma therapy, but we also demonstrated that the presence of specific cells dictates which resistance mechanism is likely to occur. This will help us to predict the resistance routes in patients and develop personalized therapies."

A personalized approach to medicine Professor Lambrechts strongly believes in the future of immunotherapy for treating different cancer types and patients: "Immunotherapy as we know it emerged only 10 years ago but is already being applied to over 30 cancer types. We've been targeting only two molecules until now, and the Grand Challenges Program will help us to target new ones with new therapies. Research into cancer vaccines is another promising immunotherapy-based way to fight cancer.

"We're on our way towards a personalized approach to medicine – and not only for cancer – thanks to incredible technological developments and extensive collaboration between research centers, hospitals and patients. The Pointillism project is an important lever in that respect."

VIB Grand Challenges This translational research program aims to increase the societal impact of our science. By teaming up with experts with complementary expertise outside of VIB, we can generate new, otherwise untapped avenues to create added value for society.

Three examples included in this edition of VIBtimes are the Soy in 1000 Gardens project (p14), the Pointillism project (p26) and several of our COVID-19 actions (p28). vib.be/grand-challenges

Flamingo Tx, another flock of potential cures In 2016, the VIB team of professor Marine, together with researchers from Ghent University and KU Leuven, revealed that the growth of aggressive skin cancer is highly dependent on the presence of a non-coding RNA gene called SAMMSON. The results of their research were published in Nature. In 2020, VIB co-founded Flamingo Therapeutics, a spin-off focusing on the development of innovative therapies based on these insights.

COO Floor Stam: "We're the only company in the world developing this type of cancer treatment in such an advanced stage.

Flamingo Tx is an international organization, but our link with Belgium and VIB is very important because of the know-how we have here." flamingotx.com

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Fighting COVID-19

A STORY OF EXTREME FLEXIBILITY AND INTENSE COLLABORATION The outbreak of a new coronavirus in 2020 posed one of VIB’s greatest challenges ever. Many researchers dropped whatever they were doing to partner up and fight COVID-19, showing great flexibility. Luckily, they didn't have to start from scratch.

Decades of research paved the way for lightning-fast investigation into possible medicines and the development of testing capacity.

On the origin of impact

"The remarkable collaboration impressed me throughout the entire crisis. The phrase 'From bench to bedside' has been given a whole new dimension" Eva Van Braeckel, Ghent University Hospital

Antibodies to the rescue The VIB lab of prof. Xavier Saelens focuses on the prevention and treatment of respiratory diseases, including influenza and beta-coronaviruses. When the new coronavirus entered the

The Contagious clinical trial was set up to characterize patients hospitalized at the Leuven University Hospital due to SARS-CoV-2 infection. Samples from patients in three disease

scene, everybody immediately mobilized to try to find a potential treatment. Xavier Saelens: "We formed the 'COVID-19 Response Team' with the lab of Nico Callewaert – consisting of ten, later twenty people – and started international collaborations with the American institute of Allergy and Infectious Diseases, the University of Texas and the German Primate Center. Working almost 24/7, we quite quickly discovered that an existing antibody derived from llamas, which binds to the SARS-CoV-1 virus that caused the SARS epidemic in 2003, also binds to the SARS-CoV-2 virus.

stages (early, moderate and late) were collected to identify factors that mediate (hyper)susceptibility to SARS-CoV-2.

Lung fluid samples revealed that monocytes – white blood cells produced by bone marrow – are the cause of intense inflammatory reactions.

"Antibodies can offer immediate protection without the need of an active immune response. This is of particular use for vulnerable people, such as the elderly, whose immune systems tend to respond poorly to vaccines. In addition, antibody-based drugs have a well-known path of development from the lab to the clinic." To test the safety and effectiveness of the llama antibody-derived drug on patients, VIB spin-off ExeVir Bio was founded in 2020.

From bench to bedside Another example of incredible collaboration and flexibility during the COVID-19 pandemic can be found within VIB's Grand Challenges Program (GCP). This program aims to increase the societal impact of research, adopting a reverse translation approach by referring back needs and questions from daily practice to the lab. In 2020, the program received additional funding from the Flemish government to link clinical observations at partner hospitals with research into the underlying molecular mechanisms of COVID-19. Bart Lambrecht, VIB group leader and pneumologist at Ghent University Hospital, was the driving force behind these new GCP tracks.

Lambrecht: "We discovered that more inflammatory molecules, called 'cytokines', are present in the lungs of ventilated intensive care patients, which enhances the risks of severe damage. Sometimes these cytokines are present in such great numbers that it causes what we call a ‘cytokine storm’. We hoped to prevent or mitigate these cytokine storms through the administration of arthritis medication in the COVAID clinical trial, funded by the Belgian Health Care Knowledge Center, but the treatments didn't result in faster healing or a greater chance of survival for participating patients. On the other hand, we gained unique insights in the true mechanisms behind SARS-CoV-2 infection and the disease it causes."

Prof. Eva Van Braeckel, pneumologist and medical COVID-19 coordinator at Ghent University Hospital, was not only involved in the COVAID project, but also in SARPAC, another project

Eva Van Braeckel Ghent University Hospital

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within the VIB Grand Challenges Program. "Since every day counts during a pandemic, we investigated the effectiveness of existing medicines in treating COVID-19," Van Braeckel explains.

"Data suggested that patients with high oxygen needs – risking further deterioration and the need for mechanical ventilation – could benefit from treatment with an immunostimulator called Leukine®, which we administered through inhalation directly into the airways. The participating patients tolerated the treatment well and showed stable or declining levels of key inflammatory markers."

Testing capacity and clear information Medicine testing and development wasn't the only contribution made by VIB. At the beginning of the COVID-19 pandemic, an internal taskforce mapped and set up the infrastructure needed for additional testing in less than three weeks. Eight Ghentbased VIB teams of volunteers tested samples to determine whether patients were infected with the virus. A few months later, British biotech company Oxford Nanopore launched its new tests based on VIB's rapid DNA sequencing technology.

"The remarkable collaboration between the government and numerous people and organizations – hospitals, study centers, and different partners in the tech ecosystem – impressed me throughout the entire crisis. I used to see Bart Lambrecht and his team only once in a while, but since the beginning of the pandemic, they have been camping out at the hospital.

We held daily check-in staff meetings with medical doctors

Another task not to be underestimated was providing people with the right information about the virus, the disease it causes and the way vaccines work. With the "Vaccins verklaard" campaign (Dutch for "Vaccines explained"), the general public received useful information about the history of vaccine research – the first vaccine dates from 1796! – and the story behind the unusually fast development of COVID-19 vaccines.

And together with VRT NWS, imec, the Institute of Tropical

and researchers to discuss all our COVID-19 patients and see whether they were eligible for one of our studies. 'From bench to bedside' – a term used to describe translational research –

Medicine, Health House and Brightlab, VIB developed the EDUbox Pandemics: a ready-made teaching package to inform young people in an attractive, interactive way.

has been given a whole new dimension."

Bart Lambrecht and Lien Van Hoecke discuss COVID-19 research at 25Y VIB

On the origin of impact

Shout out to our COVID-19 response team at the VIB-UGent Center for Medical Biotechnology

COVID-19 OUTREACH Additionally, to help the scientific community bundle their expertise and knowledge, VIB supported the Interdisciplinary Symposium on COVID-19 on June 24th, 2021. The swift action of the global scientific community resulted in a historically rapid vaccine development and growing understanding of the virus's biology. The conference had the explicit aim of helping medical and academic researchers stay up to date on the latest developments.

Almost two years after the outbreak, the pandemic is far from over. "Through intense collaborations between people with different background, we've already moved mountains in this enormous battle," Bart Lambrecht asserts.

"We knew little about the infection and how the disease would evolve, but everybody was ready to find solutions. A few mighty challenges remain. We still don't know how to obtain sterilizing immunity, which is needed to develop a vaccine that prevents infection instead of disease. And what is behind the very different individual reactions to the virus? These are important questions for basic scientists to answer in the years to come."

• With a podcast, website, fact series and social media campaign Vaccin's verklaard aimed to inform the public in Flanders about how and why vaccines are developed.

• VIB fights covid on all fronts, from preventions to diagostics and treatments. Read all about it on covid.sites. vib.be • Adrian Liston (VIB-KU Leuven Center for Brain & Disease Research) and this team worked together with illustrator Tenmei to produce children books on immunity, vaccines and COVID-19 - in different languages. They also launched Virus Fighter, an interactive virus outbreak simulator that allows you to model the effects of quarantine, social distancing and vaccination on an ongoing virus outbreak, in real time.

• Yasmine Driege, Inna Afonina and Aurora Holgado from the Rudi Beyaert lab (VIB-UGent Center for Inflammation Research) made a video to explain how COVID-19 tests work.

• Together with VRT and other partners, VIB developed Edubox Pandemie, engaging course material for high schools on viral disease.

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2021 VIB alumni award goes to WHO scientist

RAFAEL VAN DEN BERGH RECEIVES THE VIB ALUMNI AWARD 2021 On 13 October, Flemish minister of Innovation Hilde Crevits handed over the VIB Alumni Award for Societal Impact to Dr. Rafael Van den Bergh. The jury panel expressed their admiration for Rafael’s work and commitment as a former field epidemiologist and implementation scientist at Médecins Sans Frontières (MSF) and more recently as research coordinator for the WHO Attacks on Health Care Initiative.

According to the jury report, "Rafael Van den Bergh has spent in the last 10 years more than 25% of his time abroad, in lowresource settings and countries in crisis with risk for his own life, showing his altruistic attitude. He is in that sense a role model and shows a high societal engagement."

Van den Bergh's career started in 2003 at VIB/VUB as PhD researcher in the labs of profs. Jo Van Ginderachter and Patrick De Baetselier. In a collaborative project with the Virology Unit of the Institute of Tropical Medicine (ITM) in Antwerp, he studied the molecular interaction between HIV and monocytes.

Rafael Van den Bergh receives the award from minister Hilde Crevits

During a field visit in Uganda together with ITM clinical coordinator Robert Colebunders, Van den Bergh observed the immense gap between the available fundamental scientific and medical knowledge and the implementation of this knowledge in the field, especially in low-income countries and regions in humanitarian crisis or in conflict. Therefore, he joined the Operational Research Unit of MSF to put his scientific and epidemiologic knowledge to the service of humanity.

THE PANEL

RUNNERS-UP

The panel members for the VIB Alumni Award 2021

A total of nine candidates were nominated for the

were Désiré Collen, Ann Depicker, Jan Tavernier and

third VIB Alumni Award for Societal Impact. Isabel

Christine Van Broeckhoven, all scientists with a long

Vercauteren and Steven Vandenabeele, founders of

and impactful VIB career.

the VIB spin-off Aphea.Bio, finished in second place.

On the origin of impact

Research at MSF

COVID support in Belgium

“Often, we know through fundamental or clinal research which kind of care is needed. What we don’t know is how to deliver this care. This is the so-called implementation gap. MSF addresses this gap by embedding operational research into its emergency and/or humanitarian interventions,” explains Dr. Van den Bergh.

“This research is designed to assess and improve practices in health programs, to help health workers to find suitable practical solutions and to speak out about what we witness on the ground.”

During the first COVID-19 wave, Rafael also assisted as epidemiologist the MSF interventions in over 100 Belgian nursing homes for the elderly. MSF compiled its experiences in a highly mediatized report "Overgelaten aan hun lot" ("Left to their fate"). He co-authored a paper in Plos One emphasizing the massive impact on the mental well-being of the Belgian nursing home residents. Van den Bergh: “Residents expressed feelings of depression, anxiety, frustration as well as decreased meaning and quality of life. Staff felt completely unprepared for the challenges posed by the pandemic. Both the report and the paper are – hopefully - taken to heart by various Belgian authorities and health organizations in the pandemic.”

“What really excited me at MSF was the diversity of the research projects – I’m not an expert in anything, but a generalist in many things. Above all, I loved the direct and immediate impact of our research for patients, clinicians and communities. We really made a difference.”

Advocacy by publishing In his capacity as field epidemiologist, Rafael Van den Bergh has led or supported research on the field across an array of health issues, including infectious diseases, mental health, environmental health, migration, torture rehabilitation, and many more. He authored or co-authored close to 140 papers in peer-reviewed journals.

Just to give a few examples: in 2014-2015, amidst the Ebola Virus Disease outbreak in West Africa, Van den Bergh and an MSF team demonstrated the feasibility of introducing the Xpert Ebola Assay in Guinea in order to massively decrease the processing time and increase the sensitivity compared with routine diagnostic PCR procedures. The results were published in the journal Emerging Infectious Diseases. Xpert has become the standard diagnostic tool in Ebola outbreaks.

"Above all, I loved the direct and immediate impact of our research for patients, clinicians and communities.

We really made a difference."

Family man goes WHO

Another paper in International Health highlights the risks of unregulated usage of oxytocin and other labor-inducing medication in women giving birth in resource-constrained countries like Pakistan. “Poor training of nurses and midwifes, combined with unregulated availability of labor-inducing medication, carries considerable risk for mother and child during birth,” explains Dr. Van den Bergh. “This paper warns local authorities and healthcare training institutes about the dangers of current health practices in their countries.”

“Publishing in peer-reviewed journals tremendously increases the impact of our research,” says Van den Bergh. “Not only because other humanitarian organisations can learn from these experiences, but also in our advocacy work with governments and health authorities. A peer-reviewed publication is worth more than ten internal reports – it’s largely a credibility issue.”

Want to learn more about Rafael Van den Bergh's work?

Van den Bergh et al., Emerg Infect Dis., 2016; Kaelen et al., PLOS One, 2021; Shah et al., Int Health 2016

Rafael Van den Bergh has a family in Belgium with two growing children. “Combining family life with being in the field for MSF became more and more difficult,” he adds. “Therefore I switched to a coordinating research function at the WHO ‘Attacks on Health Care Initiative’. In the first three quarters of 2021 alone, over 730 confirmed attacks on health care took place in emergency-affected countries and fragile settings. These attacks deprive people of urgently needed care, endanger health care providers and undermine health systems. Here too, operational research paves the way to better advocacy and improved protection and mitigation strategies on the ground.”

ALL VIB ED TO ALUMNI ARE INVIT I N JOIN THE VIB ALUM IN. GROUP ON LINKED 33

On the origin of impact

CELEBRATING 25Y OF VIB COMMUNITY

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MARK YOUR CALENDAR Applied Bioinformatics in Life Sciences (4th edition) March 10-11, 2022 - Leuven, Belgium Crop Innovation & Business March 27-29, 2022 - Ghent, Belgium VIB Seminar 2022 April 28-29, 2022 - Veldhoven, The Netherlands Next-Generation Protein Analysis and Detection (4th edition) May 30-31, 2022 - Ghent, Belgium Recent insights into Immuno-Oncology June 16-17, 2022 - Leuven, Belgium

COLOPHON Responsible Publisher Jo Bury VIB vzw Rijvisschestraat 120 9052 GHENT BELGIUM

Editors Liesbeth Aerts Sofie Bekaert Gunnar De Winter Astrid Gadeyne Elisabeth Stes Sooike Stoops Laurien Van Dyck

All Enquiries VIB HQ Rijvisschestraat 120 9052 GHENT BELGIUM

Photography Ine Dehandschutter Rob Stevens Filip Van Loock

www.vib.be

Images Wei-Ting Chen Hannah Bertels Nikky Corthout Ellen Vandeveire

E-mail: communications@vib.be Tel.: +32 9 244 66 11