VIB-KU Leuven Center for Brain & Disease Research - Science & People 2018

VIB-KU Leuven Center for Brain & Disease Research - Science & People 2018

VIB-KULeuvenCenterfor Brain&DiseaseResearch SCIENCE&PEOPLE2018

VIB-KU Leuven Center for Brain & Disease Research - Science & People 2018

A lot can change over the course of a year. Our center took a new start in 2017 but this has not slowed us down. On the contrary, five new group leaders have joined, several with an entire team, bringing our total number of researchers and support staff to more than 300, working in 18 different VIB-KU Leuven research units. I could not have imagined a better and more fruitful first year. Together, we have done an enormous amount of exciting science. We traveled the world to talk about our results (winning prestigious prizes along the way) and invited our colleagues to Leuven for lectures and meetings.

We reached out to patients, to policy makers and to society to talk about why and how we study the brain in health and disease. We raised awareness and talked, baked, ate, swam and ran for charities that share our mission. We welcomed an enthusiastic crowd of new PhD students and saw those who graduated embark on new professional adventures at leading institutes and companies all across the globe. We teamed up with nonacademic partners to push our findings to the clinic and industry, and we are home to the newest (and largest ever) VIB spin-off: Aelin Therapeutics!

More exciting ventures are on the horizon: 2018 will be the year we supersede our borders, a year of reaching out to our different stakeholders and partners, locally and internationally, to strengthen Leuven as a global hub for neuroscience. The Leuven Brain Institute will bring all neuroscience-enthusiasts in Leuven under one roof, from social scientists to engineers, biologists and medical doctors. We are also working on a new initiative that combines the expertise of VIB, KU Leuven, UZ Leuven and imec to build new technology to transform the research and treatment of neurodegenerative diseases.

I am convinced that together we are stronger and our research will be even more impactful. Let’s keep on pushing the boundaries of knowledge to achieve our mission: a breakthrough in the cure of neuronal and neurodegenerative disorders. Patrik Verstreken Director 2018willbetheyear ofreachingout LET’SKEEPONPUSHINGTHE BOUNDARIESOFKNOWLEDGE CONTENTS 4 MEET THE NEW GROUPS 7 CBD IN NUMBERS 8 OUR RESERACH GROUPS 14 SCIENCE OUTPUT 16 TECH TRANSFER 18 OUTREACH 20 PROFESSIONAL DEVELOPMENT ASSOCIATIONS 22 PHDS 26 EXPERTISE UNITS 29 AWARD-WINNING STUDENTS 30 ALUMNI 33 SUPPORT 34 CBD IN ACTION CENTER FOR BRAIN & DISEASE RESEARCH 2018 3

VIB-KU Leuven Center for Brain & Disease Research - Science & People 2018

Why did you want to join our center? What makes it a good place to start or lead a lab? STEIN: It is a fantastic place to lead a research group, embedded within the KU Leuven, but adding significant flexibility, research opportunities, a collaborative network, and international attractiveness. SHA: For me, in one way it was by chance. When I came across the flyer for an open PI position, I did not know VIB. But the more I learned about this place, the more I realized it would be a good fit. There are lots of fly neurobiologists here, which is really helpful, especially for a new PI – the existing expertise is a big support while I get things up and running.

LUCIA: No doubt, this center is one of the best in Europe. Probably in the States there are places with a similar vibe, but in Europe I think it is quite unique. Plus, I already know the place very well obviously. I have developed a lot of tools here and I already had established a small group, so staying here meant I did not have to start from scratch. THOMAS: I have always been impressed with the research going on at VIB. I knew about the possibilities, also in terms of the available expertise and facilities. I knew there were aspects in which my group could improve and I felt that VIB would enable us to do so.

PIERRE: I have had great interactions with members of this center over the years, and it always struck me as a group of very talented scientists with genuine scientific curiosity and hunger for novel technologies. In recent years our lab has leaned more and more towards neuronal cell biology, which is a great strength of the center and a great appeal for us to push our projects forward. Also the critical mass around the center, including the KU Leuven Department of Neurosciences, the other VIB centers and NERF are a strong incentive for us. Conversely, why are you or your group a good fit for our center? STEIN: Research in my lab combines computational biology with singlecell genomics.

I think they selected us because the CBD recently decided to invest in single-cell technologies, and because there is an increasing need for bioinformatics expertise. And because gene regulation is cool of course! SHA: Why we need sleep is still a huge mystery, even though it is one of the most important animal behaviors, with broad applications in neurodegenerative and neurodevelopmental disease. For that reason, I believe I can contribute a lot to ongoing research here. My background is not in molecular biology, which in this case is a plus, I think. There are lots of molecular biologists here that are doing a great job.

They don’t need another one. LUCIA: Bart De Strooper and Wim Annaert already lead excellent groups for presenilin biology. My group can bring the extra expertise to make the presenilin program more comprehensive, all the way from kinetics to cell biology. Together, we are a power team. I think this mutual advantage was clear also to others at our center. Even at meetings abroad, people tell me how Leuven is fertile ground for familial Alzheimer’s research. PIERRE: Several CBD groups are very interested in some of the approaches that we developed, in particular human/ mouse chimeric brain models.

THOMAS: I am convinced that ion channel biology deserves a place at a life science institute like VIB. Ion channels are a very important class of proteins with an enormously broad potential for therapeutic applications, not only in neuroscience but also in the cancer field. We don’t work exclusively on neurobiological topics, but a lot of our work is very complimentary, especially for peripheral neuropathies. Several of you joined with an entire team. How do you think they can benefit from being part of our center? STEIN: The team benefits from flexible funding, new collaborative efforts, training, core facilities, and from the strong support in Drosophila as a model system for neuroscience.

LUCIA: Our research is quite in vitro, focused on mechanistic problems. By being part of a neuroscience center, we keep the context of the disease and the expertise that goes with it within close reach. That is also one of the reasons I did not go to a purely biochemical research department for example. Complex problems require complex approaches and this environment offers that. THOMAS: I think VIB offers enormous opportunities for training and I encourage everyone in my team to take full advantage. I know some members of my team eagerly started to use facilities since we joined. Another important benefit is the opportunity to get critical and constructive feedback on our own work, for example by joining the CBD seminars and meetings.

SincestartingoffastheCenterforBrain&DiseaseResearchinJanuary2017, weattractedfivenewgroupleaderstojoinourranks:SteinAerts,ShaLiu, ThomasVoets,andLuciaChavez-Gutierrezwereallappointedin2017, PierreVanderhaeghenjoinedatthestartof2018.Someofthemalreadyhadan establishedgroupandwereclosecollaborators,othersarebuildingateamfrom scratch.Frombioinformaticstoneuralcircuits,eachofthembringsauniqueset ofskillsandexpertisethatwillhelpusbuildevenstrongercollaborativeresearch linesacrossourcenter. WE’REGROWING! MEETTHENEWCBDGROUPS LuciaChavez-Gutierrez ShaLiu PierreVanderhaeghen ThomasVoets SteinAerts It always struck me as a group of very talented scientists with genuine scientific curiosity and hunger for novel technologies CENTER FOR BRAIN & DISEASE RESEARCH 2018 5

VIB-KU Leuven Center for Brain & Disease Research - Science & People 2018

PIERRE: Overall, I believe together we will create a critical mass of groups interested in complementary topics and technologies: the resulting synergy is what I am hoping for, as it will create unique opportunities of new discoveries for everyone involved. What are you most proud of professionally? THOMAS: Good question. I think our group is well known for generating better insights into temperature sensing. We have become somewhat of an international reference and that is something I am personally quite proud of. I am also very happy to see we have succeeded to attract talent, also from other departments in terms of collaboration.

We have become a local hotspot for translational research. STEIN: I’m most proud of all the PhD students that graduated in my lab and continue enjoying scientific research. Research-wise, I’m proud of our computational inventions that are used world-wide by the community, such as iRegulon and SCENIC. Service-wise I’m most proud of founding the Fly Cell Atlas community and hosting its first meeting in Leuven, thanks to strong support of the CBD.

SHA: My biggest contribution has been my Cell paper. Not because of the journal it was published in, but because of how it has challenged existing views on how sleep drive is generated in the brain. There are many papers of which you could have predicted the outcome, that confirm what you or others already thought, but this study generated a real change in thinking, and I am super proud of that. LUCIA: I feel proud that I kept my drive and passion for science, while balancing all other aspects of life. People often tell me that I am good at motivating my team so it makes me proud that I can connect with them and help them get the best out of themselves.

PIERRE: Our lab discovered a surprisingly simple way to make neurons of the cerebral cortex in a dish, using pluripotent stem cells. This started as a very exploratory project, and results came out of the blue to us. I think it illustrates the importance of basic research for biotechnology and medicine: we were initially driven by our mere curiosity about neural development, but now pluripotent stem cell-based models of corticogenesis are used worldwide in academia and industry for brain disease modelling and drug discovery.

Now that you have joined our center, what are your plans for the future? STEIN: Our mission is to decipher the genomic regulatory code, and to exploit that knowledge to predict and modulate biological processes. SHA: I’ll focus more of my lab’s effort on studying the function of sleep and on defining sleep at the cellular level. I have also come to realize that studying the circuits one by one is maybe not ideal. I would like to start using more systematic approaches. THOMAS: Our translational research efforts are all quite experimental and preliminary at the moment but I hope to expand this in the future.

My aim is to really contribute to a therapy with our research. After all, that is the final goal of every biomedical researcher. We will always keep investing in clinical applications and in collaborations that help us work towards that goal. LUCIA: The same goes for me, I really want to contribute to finding a cure for Alzheimer’s disease. It might sound cliché, but it has been my motivation from the start – and I also think we can do it. We will continue building on our current results but I also want to find other options, a plan B, C and D... PIERRE: I want to study the specificities of the human brain at the neuronal level, from genes to neural circuits, that is our main goal.

This is obviously a very challenging endeavour, but if successful, it is likely to reveal exciting insights on what makes us humans, whether in health or disease.

What should the rest of our center know about you or your team? Any mottos, traditions or fun facts you would like to share? STEIN: That we are proud of our “humid lab”, based on three pillars: the wetlab, the computational lab, and the technology & microfluidics lab. That we are engaged towards open access and open science. That hypothesisfree research is great fun. And that computational thinking rules! PIERRE: People in our lab come from all over the world, from Japan to Linkebeek: this diversity is a lot of fun and a great strength as well.

LUCIA: Hopefully people at our center are aware of our strong expertise on kinetics and structure-function, and maybe we can help out with some problems.

Besides biochemistry, we could also help with cocktails! Especially, but not limited to, piña colada. Personally, I love to dance, just as much as I love science. THOMAS: We are a lively bunch, always enthusiastic when something needs to be organized. Our team regularly gets PUBLICATIONS ERCGRANTSRUNNING 127 9 ACCOMPLISHMENTSINOURFIRSTYEARASCBD CBDINNUMBERS Together we will create a critical mass of groups interested in complementary topics and technologies 17 PHDDEFENSES NEWGROUPS 5 306 PEOPLEINTOTAL NATIONALITIES 38 together for dinner or drinks. On those occasions, tradition dictates that every new member in our team tells a dirty joke.

SHA: I would like to write a book about the origin of all the Drosophila mutant names. There are so many funny stories behind these strange names. Maybe I’ll do it when I retire? I also like to eat weird food when I travel and have tried all kinds of meat. To other culinary explorers I can recommend viper or meat from a camel’s bump. PIERRE: As for me, well when I’m not in the lab my main thrill is to sing in a rock band. We are called the Fucking Come Back. Who knows, maybe we’ll come over one day for a gig at a CBD party! We’re already looking forward to it! CENTER FOR BRAIN & DISEASE RESEARCH 2018 7

VIB-KU Leuven Center for Brain & Disease Research - Science & People 2018

LUCIACHAVEZ-GUTIERREZ LABORATORYOFPROTEOLYTICMECHANISMSMEDIATING NEURODEGENERATION Our research substantially advanced our understanding of the mechanisms operating in familial Alzheimer’s disease and put forward a novel conceptual framework for the study of both familial and sporadic forms of the disease. As next steps, we will depart from the gained insights to unravel “familial Alzheimer’s-like” mechanisms potentially contributing to the most common and sporadic form of the disease. On the translational side, we will collaborate with the Drug Discovery Unit at UCL on an original drug discovery strategy to tackle Alzheimer’s in the clinic.

MARKFIERS BIOINFORMATICSEXPERTISEUNIT Last year a number of successful collaborations on diverse topics lead to great publications; a trend we hopefully will continue in the coming year. We aim to focus on the establishment of state of the art automated work flows and many diverse collaborations, with a focus on single cell and spatial transcriptomics. RESEARCHGROUPS LOOKINGBACK,MOVINGFORWARD STEINAERTS LABORATORYOFCOMPUTATIONALBIOLOGY Our highlights of 2017 include the start of an ERC Consolidator Grant; the publication of our new bioinformatics method SCENIC, which was quickly adopted by the community; our single-cell sequencing of the entire adult fly brain that we accomplished in one year and that lead to exciting collaborations with the Verstreken and Liu labs; our involvement in the Human Cell Atlas and our leading role in the foundation of the Fly Cell Atlas consortium.

We look forward to more single-cell data, which will provide an exciting foundation to discover new regulatory “recipes” of cell types, during development and aging. In our human research line we are building a large “single-cell systems biology” resource of cancer cell state transitions. We are also creating new microfluidics solutions for single-cell migration studies and are exploring the possibilities of organ-on-chip (tumoroid-on-chip). BARTDESTROOPER LABORATORYFORTHERESEARCHOF NEURODEGENERATIVEDISEASES After about 20 years of work and in collaboration with Lucia ChavezGutierrez, we have finally cracked the mystery how mutations in presenilin cause Alzheimer’s.

We established a novel mouse/human chimeric model for Alzheimer’s and got single cell sequencing up and working: ready to move into the study of the cellular phase of Alzheimer’s disease.

This year, we will provide the single cell analysis of the inflammatory component and the spatial transcriptomic profile of the full cellular component of Alzheimer’s in a knock-in model for the disease. We have been able to transplant human microglia in mouse brain and will now be able to establish the role of human microglia in the neurodegeneration of Alzheimer’s disease. WIMANNAERT LABORATORYFORMEMBRANETRAFFICKING We developed, with imec, magnetic nanoparticles that can be targeted to lysosomes and allow for their subsequent isolation. The high yield and purity permits lysosomal proteome and lipidome profiling and the identification of disease-related alterations in this key subcellular compartment.

Given that abnormalities in endo-lysosomal flux are emerging as a central theme in neurodegenerative diseases, including Alzheimer’s, Parkinson’s and ALS, our methodology provides a new gateway to profile changes at subcellular resolution which may identify altered signaling or sorting routes that impact lysosomal proteostasis. JORISDEWIT LABORATORYOFSYNAPSEBIOLOGY We uncovered new cell surface interactions regulating synaptic identity and synaptic function in hippocampal circuits. A new challenge will be to start exploring how these mechanisms regulate connectivity, synaptic transmission and information processing in cortical circuits.


VIB-KU Leuven Center for Brain & Disease Research - Science & People 2018

ROSEGOODCHILD LABORATORYFORDYSTONIARESEARCH Last year we welcomed several new lab members in our growing team and published a pair of review articles on TOR1A-dystonia and lipid synthesis. We also published the first results from a long-running collaboration on striatal electrophysiogical defects in dystonia mouse models. Overall, new data from several projects is continuing to point to abnormal lipid metabolism in TOR1A-dystonia. We hope to start publishing these in 2018, as well as our research on the mechanisms underlying a newly identified severe congenital form of TOR1A disease.

MATTHEWHOLT LABORATORYOFGLIABIOLOGY Last year we made significant progress in understanding the degree of molecular heterogeneity between astrocytes in the CNS. This year, we hope to start investigating the functional consequences of this heterogeneity for CNS development and neuronal function. NATALIAGUNKO ELECTRONMICROSCOPYEXPERTISEUNIT Our highlights of 2017 include having a new “two-in one” combined light and electron imaging device (SECOM) installed and running, and Katlijn Vints winning the image competition at the Crick Electron Microscopy Opening symposium in London. We also co-authored 6 scientific papers.

For this year, we are excited to do push things further using the new SECOM and with our new 3D imaging approaches, together with the light microscopy expertise unit.

ADRIANLISTON TRANSLATIONALIMMUNOLOGYLABORATORY Last year we have made major advances in identifying and treating primary immunodeficiencies. Through developing new mouse models of these diseases and testing treatments already approved for human use, we have been able to move straight to clinical trials. Over the next years we will get the clinical trial results back, and hopefully will be able to make recommendations on changing the current therapeutic approach for these patients. SEBASTIANMUNCK LIGHTMICROSCOPYEXPERTISEUNIT We are looking back on a prosperous 2017, where we reached out to the community by organizing an Analysis Conference in Portugal (NEUBIAS), trained many students in our summer school and image processing workshop, and by having our new combined light and EM (Secom) device installed.

We are excited about using this new machine to its full capacity in 2018 and are also looking forward to enabling fantastic science with our new approaches on 3D imaging that are about to materialize in the next year. SHALIU LABORATORYOFSLEEPANDSYNAPTICPLASTICITY For us, 2017 was a big year: the start of the lab and an ERC grant! We are excited that a pre-print of the first collaborative project with the CBD (the single cell atlas of the fly brain, with the groups of Stein Aerts and Patrik Verstreken) is already out. This year, I look forward to expanding our team and our output as we explore the role and mechanisms of sleep in the brain.


VIB-KU Leuven Center for Brain & Disease Research - Science & People 2018

LUDOVANDENBOSCH LABORATORYOFNEUROBIOLOGY Last year, we discovered that selective inhibition of histone deacetylase 6 (HDAC6) has a therapeutic effect on inherited as well as acquired neuropathies. Moreover, these inhibitors also reverse the axonal transport defects in motor neurons obtained from ALS patients. In 2018, we will further investigate the molecular mechanisms responsible for the selective motor neuron death using motor neurons derived from induced pluripotent stem cells.

DIETMARSCHMUCKER NEURONALWIRINGLABORATORY In the continuous effort to elucidate basic mechanisms of neuronal wiring specificity my group excelled in 2017 and majorly advanced on all our projects. I am looking forward to help them to reap the benefits of their outstanding work in publishing important stories in 2018. This includes work on CNS synapse formation, human/vertebrate DSCAM, a novel protein network controlling axon branching, evolution and function of protocadherin diversity, as well as our first work on axon regeneration mechanisms. We are also looking forward to collaborating with the de Wit and Vanderhaeghen labs, as well as with the groups of Laurent Nguyen (University of Liège) and Fadel Tissir (Université Catholique de Louvain) on our “SYNET” project, ‘Temporal and spatial control of synaptic patterning in collaboration: from basic mechanisms to human-specific innovations and diseases’, for which we received our recent Excellence of Science network grant from FWO/FNRS.

FREDERICROUSSEAU&JOOSTSCHYMKOWITZ SWITCHLAB The incorporation of Aelin Therapeutics is without a doubt the biggest highlight of 2017 for our laboratory. In 2018 we look forward to helping to make this company a success and to continue to develop the targeted aggregation platform that we created at the Switch Laboratory. In particular, we have high hopes for novel applications, such as in cancer or viral infections. THOMASVOETS LABORATORYOFIONCHANNELRESEARCH In 2017, we elucidated the molecular basis of noxious heat sensing, by identifying the full set of heat sensors (all TRP channels!) that are involved, and by developing a mouse model that is fully devoid of heat-induced pain.

For 2018, we aim to specifically pinpoint where and when these channels become activated in vivo, and how they can be specifically targeted to treat chronic pain. In addition, we foresee important progress in the clinical translation of our research with the initiation of three clinical studies related to pain, bladder overactivity and diabetes.

PIERREVANDERHAEGHEN STEMCELLANDDEVELOPMENTALNEUROBIOLOGY Last year was very fruitful for our ERC project: we identified a specific repertoire of more than 30 human-specific genes expressed during human brain development, and now follow up on their functional characterization, which is already quite promising. For us, 2018 brings a new start, as our lab joins the CBD. We are excited to intensify our existing collaborations within the center, for example on humanized models for neurodegenerative diseases and on studying the temporal and spatial control of synaptic patterning. PATRIKVERSTREKEN LABORATORYOFNEURONALCOMMUNICATION We have made important discoveries that uncover how neurodegenerative conditions, both pathogenic mutations in Parkinson’s disease and tauopathies, affect synaptic cell biology.

We will now step up our efforts assess the functional consequences of these discoveries in vivo by starting to use mouse human brain chimera models as well as define the most vulnerable cell types in a living Drosophila brain using single cell RNA sequencing. RESEARCHGROUPS LOOKINGBACK,MOVINGFORWARD CENTER FOR BRAIN & DISEASE RESEARCH 2018 13

VIB-KU Leuven Center for Brain & Disease Research - Science & People 2018

Can you summarize the significance of your findings for people outside your field? SARA: We have developed a computational method to infer the gene regulatory networks underlying the cell types present in a single-cell RNA-seq dataset. This information provides a better understanding of the cell types or states, and highlights “master regulators” that can be used as potential drug targets. MARIA: We have elucidated the pathogenic basis of Familial Alzheimer’s disease caused by mutations in Presenilin, the catalytic core of the γ-secretase protease, or in Amyloid Precursor Protein (APP), its substrate.

Processing of APP by Presenilin generates Aβ peptides, and we demonstrated that mutations destabilize the γ-secretase-APP interactions and promote the ‘premature’ dissociation of the substrate thus generating longer, more aggregation-prone Aβ peptides. Our results suggest that stabilizing the interactions between γ-secretase and APP-derived substrates could become a therapeutic approach to tackle Aβ production in Alzheimer’s disease. STEPHANIE: Working in the field of primary immunodeficiency disorders, we described a new mouse model for severe combined immunodeficiency (SCID), which recapitulates the key clinical features of SCID patients suffering of both immunodeficiency and autoimmunity (leaky SCID).

Importantly our model proposed a novel efficient therapeutic approach for this disease.

Why do you think the paper made it to such a good journal? SARA: Although single-cell RNA-seq has become a more broadly used method, and many researchers are interested in learning about the regulatory mechanisms in their systems, there were still no analysis tools that exploited the higher resolution of scRNA-seq data to easily address these questions. That’s why the publication of our method was so timely. MARIA: Getting the study into a journal with such a broad readership depended heavily on the fact that we were answering one of the significant open questions in the Alzheimer’s field and that it generated insights that may hopefully guide future drug discovery studies.

The rest is good timing.

STEPHANIE: We provide strong preclinical evidence of drug efficiency to treat a rare disease, directly proposing patient clinical trials. Since the treatment is already approved for arthritis, it could be rapidly repurposed for leaky SCID patients. In addition, our model is available for further pre-clinical assays, including gene therapy. When did you realize you were on to something really interesting? SARA: The initial idea of the project already sounded very interesting. However, it wasn’t until we tested the full pipeline, and it recovered the relevant cell types plus some known regulators, that we confirmed it could actually work.

It was also very exciting when we saw that our tool (SCENIC) was much better at identifying cancer-related cell states than regular clustering methods.

MARIA: Very early on, the feeling of excitement surrounded us mostly because we were answering a question that we had all been extremely curious about. However, I still remember the day when I TALKING2017RESEARCH RESEARCHOUTPUTINNUMBERS Publishinganimportantdiscovery ishardwork.SaraAibar(postdocin theAertslab),MariaSzaruga(PhD studentintheChavez-Gutierrezand DeStrooperlabs)andStephanie Humblet-Baron(postdocinthe Listonlab)tellusabout theirexperience. realized that the data we were collecting was correlating with the age of onset of the disease. I was running around the lab searching for my supervisor to share the news.

It gave us enormous energy to keep on digging and understand what was really going on.

STEPHANIE: When I started to work with this model I already knew which gene was mutated (the one encoding the Artemis protein). However, when I saw the mice for the first time I could tell that they were developing the exact same symptoms that we see in the clinic. I knew that other mouse models working on this gene had never shown leaky SCID symptoms, so we needed to explore the model in depth. The other key moment was after treating our mice with the drug (CTLA4-Ig) – it completely blocked disease, making this a very valuable project with new therapeutic opportunities for patients.

What are you personally most proud of? SARA: It is a very useful method! Many people are interested in applying SCENIC to their own dataset, and in several studies it has already provided cellular states or regulators that were later confirmed to be clinically relevant.

STEPHANIE: This work can be seen as translational medicine, with direct therapeutic benefit for the patients. Of course this is very rewarding. The fact that we were able to better understand the mechanism of the disease was also valuable to me.

How did the expertise (units) in our center make a difference for this story? SARA: Several groups started adopting single-cell genomic methods in early phases. Their experience and comments about the analysis of the data were very useful when we were starting the project. In addition, although in the paper we only present the results on public data, the availability of in-house datasets to test and refine our method enabled us to get very relevant feedback. STEPHANIE: The FACS core was instrumental, as this project relied heavily on this technique.

MARIA: On a more general note, the whole community at our center made us feel supported and backed up.

It is much easier to stay motivated when surrounded by passionate scientists. We could rely on the expertise present at the center to help us mature our ideas, especially to push through during the revision process. Do you have any advice for others? STEPHANIE: Always envision your project as a story to write and tell. When you find a new result ask what would be the next question and continue to explore it further.

MARIA: Keep your eyes on the goal but most of all enjoy the journey! The process of untangling complex questions and learning can be as rewarding as showing what you found to the world. Aibar et al. Nature Methods 2017 Humblet-Baron et al. J Allergy Clin Immunol 2017 Szaruga et al. Cell 2017 Weprovidestrongpre-clinicalevidenceofdrug efficiencytotreatararedisease Keepyoureyesonthegoalbutmostof allenjoythejourney! 34% In top 5% of all journals in the field (Nature, Cell, eLife, Neuron, EMBO...) 35% In top 25% of all journals in the field (HMG, EMBO Reports, JBC, FASEB...) 127 = publications in 2017 2.54 publications per week 15 CENTER FOR BRAIN & DISEASE RESEARCH 2018

VIB-KU Leuven Center for Brain & Disease Research - Science & People 2018

Truly innovative research leads to the build-up of valuable intellectual property, but whether it is the discovery of a new therapeutic target or the development of a novel technology, bringing it to the clinic or industry is not always trivial. We constantly work together with the Technology Transfer team at VIB, mainly through Floor Stam and Wim Grunewald, and with VIB Discovery Sciences to make this happen. We foster creative partnerships with clinical and basic investigators at KU Leuven or other research centers. We aim for long-term strategic partnerships with the pharmaceutical industry with a mutual interest in translating fundamental insights into hypotheses that can be tested in the clinic.

We are convinced that target validation and drug discovery should be steered with deep mechanistic biology insights, especially in the early stages.

The risk-averseness of private investors and the poor reputation of investing in the neurological disease field means that forging partnerships is more challenging than ever. That is why we want to explore different, less traditional models of collaboration, through joint ventures, patient charity partnerships and mixed models. We have also hired a ‘flying’ research technician, Alfonsa Laragione, who will support translational research projects at our center, wherever opportunities arise. TECHTRANSFER Our labs are a breeding ground for ideas and collaborations with pharma partners. We are for example collaborating with industrial partners on single-cell sequencing and on synaptic cell biology.

We are also developing partnerships for drug discovery and development projects, for example to identify gamma-secretase stabilizers and inhibitors. TECHNOLOGYDEVELOPMENTANDDRUGDISCOVERY BACE1 is one of the enzymes involved in the production of amyloid-beta in Alzheimer’s disease. BACE1 antibodies developed in the lab of Bart De Strooper were licensed to Denali, a San Francisco-based pharmaceutical company, to develop new therapeutics for Alzheimer’s disease. A biomarker test for BACE1 was also licensed to ADx and is currently being commercialized. BACE1TARGETING The research from the lab of Frederic Rousseau and Joost Schymkowitz (Switch lab) is the foundation of VIB’s newest and largest-ever spin-off company Aelin Therapeutics.

The team secured an investment of 27 million € to pioneer a novel modality in drug development to induce cell death, for example for new antibiotics or in cancer treatment. The technology, branded Pept-ins™, harnesses the power of protein aggregation to specifically induce the functional knockdown of a target protein.

AELINTHERAPEUTICS FloorStam JoostSchymkowitz FredericRousseau WimGrunewald AlfonsaLaragione INDUSTRIAL REVENUEIN2017 PATENTAPPLICATIONS IN2017 SPIN-OFF 1.3M€ + + 5 1 17 CENTER FOR BRAIN & DISEASE RESEARCH 2018

VIB-KU Leuven Center for Brain & Disease Research - Science & People 2018

OUTREACH Cupcakes for ‘Stichting Alzheimer Onderzoek” Bart De Strooper baking 200 cupcakes Mendelcraft workshop at the Kids University News crew in our labs Policy makers visit to discuss animal research Running at the Warmathon Princess Astrid visits the Voets lab The Van Den Bosch lab at the Amsterdam City Swim for ALS CENTER FOR BRAIN & DISEASE RESEARCH 2018 19

  • Exchange know-how between labs
  • Inform about expertise and services of the scientific facilities and units at our center
  • Build bridges between the center management and the scientific support staff, including all lab managers and lab technicians
  • Have a positive impact on the research center and VIB by sharing ideas and solutions Represents all postdocs and staff scientists at VIB CBD representatives: Vinoy Vijayan (Verstreken lab) & Emanuela Pasciuto (Liston lab)
  • Monthly networking in Brussels with postdoc representatives of different VIB Centers
  • Yearly postdoc day on career development
  • Stay up to date via THE SSA ORGANIZES:
  • Monthly meetings about a specific topic, ranging from safety policy to new technologies - we invite speakers who share their expertise on innovative technologies such as single cell analysis, RNA Scope, CRISPRCas technology or electrophysiology.
  • - Speakers may also provide a basic introduction to specific topics such as statistics or first aid.
  • Discussions between scientific support staff about particular experimental issues
  • Ad hoc working groups that can help putting new ideas and initiatives into action The SSA is also involved in the organization of the VIB seminar and provides input for VIB trainings tailored to technical support staff, such as the VIB CRISPR User meeting that took place on Jan 31st, 2017. Represents all postdocs and staff scientists at the CBD President: Vinoy Vijayan (Verstreken lab) & Anupam Das (Goodchild lab)
  • Organization of Tuesday progress seminars and pizza lunch: Aleksandra Brajic (Liston lab), Luis Ribeira (de Wit lab) & Dan Dascenco (de Wit lab)
  • Lunches with speakers of the Thursday distinguished lectures series: Emanuela Pasciuto (Liston lab) & Annerieke Sierksma (De Strooper lab)
  • Coordination of the monthly happy hour: Vinoy Vijayan (Verstreken lab)
  • All CBD postdocs and staff scientists are automatically included on the postdoc mailinglist Meetings are every first Tuesday of every month (unless indicated differently) at noon in room 07.339.

Get in touch with questions and suggestions or let us know if you want to join the organizing committee: The Scientific Support Association (SSA) is run by and for technicians All CBD postdocs and staff scientists are represented by the postdoc association (PDA) at our center and the VIB-wide Postdoc Committee (PDC). On both levels, the aim is to foster a sense of community and to provide resources for career and personal development. Have an idea or want to get involved? Get in touch! SCIENTIFICSUPPORT ASSOCIATION GOALS VIBPOSTDOCCOMMITTEE IMPLEMENTATION CBDPOSTDOCASSOCIATION GETINVOLVED PDA SSA CENTER FOR BRAIN & DISEASE RESEARCH 2018 21

Three days of PhD classes for all newbies (pictured) were followed by two days of symposium for all PhD students, with the location alternating between imec and Gasthuisberg. During the PhD classes, the first-year PhD students had the chance to meet each other, present their projects and share their dreams for the future. They were introduced to the different CBD and NERF PIs and their work and discussed science, career development and everything in between. Another major goal of the PhD class was for the students to get acquainted with the cutting-edge technologies available at our expertise units and the VIB core facilities.

The PhD class was concluded with a social event organized by the students themselves. On the final two days of the week, all other PhD students joined in for a symposium with internationally renowned speakers, poster sessions and company workshops.


STEVEN: My friends, the great atmosphere, the happy hours. ROELAND: Happy hours with the Verstreken lab and others! JOE: The state-of-the-art equipment, and the many networking events. What do you like most about your new job? HERMIEN: I meet a lot of people, with all kinds of different jobs. I like making and giving presentations, teaching people and this is also an important part of my job.

My colleagues are also very nice. LAURA: What I like of this job is the possibility to exploit my scientific background and build up new knowledge in the patent law field. Plus, working for a pharma company is very exciting.

STEVEN: The absolute freedom I get to pursue whatever I think is interesting, and the extremely collaborative environment. JOE: The fact that it builds upon the skills from my PhD to further develop my long-term research goals Why did you choose that job, company or lab? HERMIEN: A combination of reasons: I was looking for a job that combines science and social interaction. For myself, I find basic research very interesting, but it can also be very slow and frustrating. So I wanted to go for more applied science. Having the sales aspect in my job was actually not planned, but I like to try new things.

Another factor was the location, as I was looking for a job close to home. STEVEN: Because of the exciting research environment.

ROELAND: Deciding what to do after my PhD was not easy. At the SfN meeting in San Diego, I talked with Xinnan Wang, and she invited me to her lab at Stanford to present my work. We continued discussions over the following months, and since I am very interested in translational research, we worked out an exciting project, where I am able to collaborate with companies but still develop my own ideas. JOE: They are leaders in their field and experts in research areas and techniques that compliment my research interests.

Any advice for other PhD students? HERMIEN: This is a difficult question, as the experience of doing a PhD is different for everyone.

I was quite lucky with my project, my supervisors, the colleagues and the available equipment, all of which have a high impact on your PhD experience. What I think is important is to always think one step ahead and not lose sight of the bigger picture. Try to involve as many people as possible in your research. Try to develop your soft skills: defining the problem (this is sometimes already half of the work), explaining the science (also to non-experts), making other people enthusiastic about your work, building your network... These skills are important in every job!

LAURA: My advice to other PhD students is to exploit the many opportunities at VIB and KU Leuven to strengthen not just your scientific but also your soft skills. Those will be useful later on, whatever you decide to do. STEVEN: I would say, don’t stress out too much, it will work out. ROELAND: My advice would be to define what your passion is and look for opportunities that are out there that can help you get there. Importantly, you will need to take action, don’t just wait until opportunities come to you, create your own.

JOE: Stay motivated and focused. In the end, things always work if you do.

It always seems impossible until it’s done. Once you have reached that milestone of obtaining your PhD, how do you look back and what new adventures await? We asked some of our recent graduates. Where do you work now and what do you do exactly? HERMIEN: I am a product specialist at Biognost. We distribute products, mainly in the field of autoimmunity and infectious serology. Our customers are hospital labs, private labs, but also contract research organizations. My job is to give presentations and workshops, to train people how to work with our products, and to maintain a good relationship with our customers.

Next to the general portfolio, my specialty within the company is neurodegeneration, which is still quite new. LAURA: I am currently working for a pharma company in Switzerland. I entered the intellectual property field, my aim is to become a European patent attorney. This requires a training period (which is what I am doing now) and to pass exams for the qualification.

STEVEN: I started a postdoc at Stanford University in the lab of Aaron Gitler. ROELAND: I also work at Stanford University, in the lab of Xinnan Wang. I work on two projects: one on developing an early biomarker for Parkinson’s disease and another in which we develop a specific inhibitor for Miro, since several Parkinsonrelated mutations impair Miro removal and delay mitochondrial degradation. JOE: I have started a post-doc at Baylor College of Medicine, researching neurodegenerative diseases using large screening platforms and mouse models of disease.

WENTING: I am working as a postdoctoral researcher at CBD as well as the stem cell institute at KU Leuven.

ISABEL: I’m currently still in the CBD but looking for post-docs abroad. Preferably in a different field to be able to learn different approaches and points of views. How do you look back on your PhD experience? HERMIEN: With a smile! Knowing what I know now, I would definitely do it again. The people I met and the skills I developed were important for shaping me into who I am now. LAURA: I think the PhD was a very interesting experience, definitely helpful for the next professional steps. STEVEN: I am very satisfied. I think I got the most out of it.

ROELAND: My time as a PhD-student was both exciting and frightful. Exciting, learning how to handle a project, trying out new techniques, discussing and troubleshooting, etc. Frightful, will I ever finish this project, get it published and be able to graduate? I look back with a lot of appreciation for my colleagues and for my mentors that enabled me to work in such an excellent scientific environment. A scientific discovery is never made by one individual, it takes a hard working team. JOE: My PhD was challenging but very rewarding. It was a time of a lot of personal and professional growth.

ISABEL: Even when the PhD could look at some point very frustrating and you may feel that you are stuck without doing or learning anything new; once you start talking with people from other fields or institutes you realized how much experience you actually acquired. Something I took for granted when I was in the lab!


THEFACSCOREISGROWING VIB is investing in a FACS Core facility, with a site in Leuven and a site in Ghent. On January 1st, the existing Leuven FACS Core became the VIB-KU Leuven FACS Core, jointly hosted by the Center for Cancer Biology and the Center for Brain & Disease Research. Adrian Liston remains the core’s director and Pier Andrée Penttila the core manager. From our Center, Christèle Nkama is a technician at the core and Matthew Holt and Susan Schlenner are on the user committee.

  • Thanks to some exciting recent and upcoming investments, the core continues to grow. These new investments make the FACS core the best-equipped one in Belgium, and one of the very top in Europe! BD Symphony, a 5-laser/28-color flow cytometry analyzer, currently the most powerful analyzer on the market, and the only one in an academic setting in Belgium; acquired via a Hercules grant (promoter Adrian Liston, co-promoters include Matthew Holt and Bart De Strooper) BD Influx, for Index sorting; equipped with 4 lasers and 16 colors, housed under a BSL2 biosafety cabinet to sort infectious and human samples; acquired via the same Hercules grant Amnis ImageStream, which combines the analysis of flow cytometry and microscopy into one machine; acquired via a KU Leuven small and medium equipment grant (promoter Adrian Liston, co-promoters include Wim Annaert) FACS Melody, Cancer foundation grant (promoter Thierry Voet (KU Leuven), co-promoters include Stein Aerts)
  • Immunology screening platform available through Stephanie Humblet-Baron (Liston lab)
  • New equipment from the Center for Cancer Biology is being integrated (AriaIII and Verse)
  • We hope to acquire a CyTOF via a new Hercules grant (promoter Frederik De Smet (KU Leuven), co-promoters include Adrian Liston, Matthew Holt, Bart De Strooper and Joost Schymkowitz) NEWINVESTMENTSIN2017 NEWINVESTMENTSIN2018 What is your background and how did you end up as our single-cell analytics and microfluidics expert?

I’m a chemical engineer by training and did my PhD in computational biology. My PhD focused on mitochondrial biogenesis and the role of mitochondrial genome drift in aging and degenerative diseases. It is intriguing to observe a mosaic pattern of mitochondrial DNA mutations in seemingly homogeneous tissue. Some cells have a high load of mutations, whereas the neighboring ones don’t. My project took computational approaches using stochastic modeling techniques to understand the origin of this heterogeneity.

That project was the beginning of my single cell interest and it also made me realize the importance of bridging the computational and experimental domains.

I wanted to explore and develop my wet-lab skills. It can be difficult to switch so radically, but I got this opportunity during my postdoc. As part of a knowledge transfer fellowship offered by Luxembourg, I had a chance to work in a lab at Caltech focusing on single cell proteomics using microfluidics technology. The idea of the fellowship was to bring the expertise to Luxembourg to set up a single cell analysis facility in a research institute focusing primarily on Parkinson’s disease. When I learned about this position, setting up a single cell facility at CBD in Leuven, I applied immediately.

What do you like about this new challenge of starting up the expertise unit at our center?

I’m interested in technology development and this is exactly what I like about my new position here. Our single cell expertise unit is not just about servicing, we also want to develop new methods. Together with the group of Stein Aerts, we are trying to develop novel assays for single cell transcriptome, epigenome and proteome profiling based on droplet/ nanowell platforms. If you have a related research problem, we can always discuss it, even if it means developing new methods. You also collaborate a lot with Mark Fiers who leads our bioinformatics platform.

Yes, of course. Our projects inherently have high computational requirements, so before actually starting the experiments, I encourage you to discuss the bioinformatics with Mark Fiers and Stein Aerts.

Our analysis pipeline goes from the experimental design to sample preparation, single cell analysis and library processing. What comes after – data analysis and interpretation – is a big endeavor! In terms of equipment, what are you hoping to add? From my experience, we are well equipped. The core has access to a broad range of tools, either via VIB or KU Leuven. VIB’s tech watch also helps us get access to some of the key emerging technologies on the market. Single cell analytics is a new field and many technologies are still under development. What I want for next year doesn’t exist yet.

We hope to develop some of these technologies ourselves! Spatial transcriptomics is something that we want to set up soon, with funding from a Hercules grant. Single cell proteomics is another technique I am hoping to add. Oligo-tagged antibodies are a powerful tool for protein quantification and we hope to integrate this with droplet-based assays to increase the throughput of single cell proteome profiling.

You have big plans! How busy are things at the single cell unit? Quite busy, actually! There are several collaborative and developmental projects underway at the single cell core. If you or your team have any questions requiring a single cell approach, just get in touch with me. SINGLECELLANDMICROFLUIDICS Have you met Suresh Poovathingal? He joined the CBD in 2017 to lead our newest single cell expertise unit. SureshPoovathingal CENTER FOR BRAIN & DISEASE RESEARCH 2018 27

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