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

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

VIB-KU Leuven Center for
Brain & Disease Research
VIB-KU Leuven Center for Brain & Disease Research - Science & People 2018
LET’S KEEP ON PUSHING THE
      BOUNDARIES OF KNOWLEDGE
      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
                                                                                                                             CONTENTS
      impactful. Let’s keep on pushing the boundaries of knowledge to achieve our mission:                                    4   MEET THE NEW GROUPS
      a breakthrough in the cure of neuronal and neurodegenerative disorders.
                                                                                                                              7   CBD IN NUMBERS
      Patrik Verstreken
                                                                                                                              8   OUR RESERACH GROUPS
      Director
                                                                                                                             14   SCIENCE OUTPUT
                                                                                                                             16   TECH TRANSFER

                                                                                                     2018 will be the year
                                                                                                                             18   OUTREACH
                                                                                                                             20   PROFESSIONAL DEVELOPMENT ASSOCIATIONS

                                                                                                     of reaching out         22
                                                                                                                             26
                                                                                                                             29
                                                                                                                                  PHDS
                                                                                                                                  EXPERTISE UNITS
                                                                                                                                  AWARD-WINNING STUDENTS
                                                                                                                             30   ALUMNI
                                                                                                                             33   SUPPORT
                                                                                                                             34   CBD IN ACTION

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VIB-KU Leuven Center for Brain & Disease Research - Science & People 2018
Why did you want to join our center?         Conversely, why are you or your             team. I think this mutual advantage was
                                                                                                                            What makes it a good place to start          group a good fit for our center?            clear also to others at our center. Even
                                                                                                                            or lead a lab?                                                                           at meetings abroad, people tell me how
                                                                                                                                                                         STEIN: Research in my lab combines          Leuven is fertile ground for familial
                                                                                                                            STEIN: It is a fantastic place to lead       computational biology with single-          Alzheimer’s research.
                                                                                                                            a research group, embedded within            cell genomics. I think they selected us     PIERRE: Several CBD groups are very
                                                           Sha Liu
                                                                                                                            the KU Leuven, but adding significant        because the CBD recently decided to         interested in some of the approaches
                                                                                                                            flexibility, research opportunities,         invest in single-cell technologies, and     that we developed, in particular human/
                                                                                                             Thomas Voets   a collaborative network, and                 because there is an increasing need for     mouse chimeric brain models.
                                                                                                                            international attractiveness.                bioinformatics expertise. And because       THOMAS: I am convinced that ion
                                                                                                                            SHA: For me, in one way it was by            gene regulation is cool of course!          channel biology deserves a place at a life
                                                                                                                            chance. When I came across the flyer for                                                 science institute like VIB. Ion channels
                                                                                                                            an open PI position, I did not know VIB.                                                 are a very important class of proteins
                                                                                                                            But the more I learned about this place,                                                 with an enormously broad potential
                                                                                                                            the more I realized it would be a good                                                   for therapeutic applications, not only
                                                                                                                            fit. There are lots of fly neurobiologists                                               in neuroscience but also in the cancer
                                                                                                                            here, which is really helpful, especially
                                                                                                                            for a new PI – the existing expertise is
                                                                                                                                                                         It always struck me                         field. We don’t work exclusively on
                                                                                                                                                                                                                     neurobiological topics, but a lot of our
                  Stein Aerts                                                                                               a big support while I get things up          as a group of very                          work is very complimentary, especially
                                                                                                                            and running.
                                                                                                                            LUCIA: No doubt, this center is one of
                                                                                                                                                                         talented scientists                         for peripheral neuropathies.

                                                                                                                            the best in Europe. Probably in the States   with genuine                                Several of you joined with an entire

                                                                                                                                                                         scientific curiosity
                                                                                                                            there are places with a similar vibe,                                                    team. How do you think they can
                                                                                                                            but in Europe I think it is quite unique.                                                benefit from being part of our center?
                                                                         Pierre Vanderhaeghen                               Plus, I already know the place very well     and hunger for
                                                                                                                            obviously. I have developed a lot of tools                                               STEIN: The team benefits from flexible
                                                                                                                            here and I already had established a         novel technologies                          funding, new collaborative efforts,

      WE’RE GROWING!
                                                                                                                            small group, so staying here meant I did                                                 training, core facilities, and from the
                                                                                                                            not have to start from scratch.                                                          strong support in Drosophila as a model
                                                                                                                            THOMAS: I have always been impressed                                                     system for neuroscience.
                                                                                                                            with the research going on at VIB. I knew                                                LUCIA: Our research is quite in vitro,

      MEET THE NEW CBD GROUPS
                                                                                                                            about the possibilities, also in terms of                                                focused on mechanistic problems. By
                                                                                                                            the available expertise and facilities.      SHA: Why we need sleep is still a huge      being part of a neuroscience center, we
                                                                                                                            I knew there were aspects in which my        mystery, even though it is one of the       keep the context of the disease and the
                                                                                                                            group could improve and I felt that          most important animal behaviors, with       expertise that goes with it within close
                                                                                                                            VIB would enable us to do so.                broad applications in neurodegenerative     reach. That is also one of the reasons
                                                                                                                            PIERRE: I have had great interactions        and neurodevelopmental disease. For         I did not go to a purely biochemical
                                                                                                                            with members of this center over the         that reason, I believe I can contribute     research department for example.

      Since starting off as the Center for Brain & Disease Research in January 2017,                                        years, and it always struck me as a
                                                                                                                            group of very talented scientists with
                                                                                                                                                                         a lot to ongoing research here. My
                                                                                                                                                                         background is not in molecular biology,
                                                                                                                                                                                                                     Complex problems require complex
                                                                                                                                                                                                                     approaches and this environment
      we attracted five new group leaders to join our ranks: Stein Aerts, Sha Liu,                                          genuine scientific curiosity and hunger      which in this case is a plus, I think.      offers that.

      Thomas Voets, and Lucia Chavez-Gutierrez were all appointed in 2017,                                                  for novel technologies. In recent years
                                                                                                                            our lab has leaned more and more
                                                                                                                                                                         There are lots of molecular biologists
                                                                                                                                                                         here that are doing a great job.
                                                                                                                                                                                                                     THOMAS: I think VIB offers enormous
                                                                                                                                                                                                                     opportunities for training and I
      Pierre Vanderhaeghen joined at the start of 2018. Some of them already had an                                         towards neuronal cell biology, which         They don’t need another one.                encourage everyone in my team to take
      established group and were close collaborators, others are building a team from                                       is a great strength of the center and a      LUCIA: Bart De Strooper and Wim             full advantage. I know some members of
                                                                                                                            great appeal for us to push our projects     Annaert already lead excellent groups       my team eagerly started to use facilities
      scratch. From bioinformatics to neural circuits, each of them brings a unique set                                     forward. Also the critical mass around       for presenilin biology. My group            since we joined. Another important
      of skills and expertise that will help us build even stronger collaborative research                                  the center, including the KU Leuven          can bring the extra expertise to            benefit is the opportunity to get critical

      lines across our center.                                                                                              Department of Neurosciences,
                                                                                                                            the other VIB centers and NERF
                                                                                                                                                                         make the presenilin program more
                                                                                                                                                                         comprehensive, all the way from kinetics
                                                                                                                                                                                                                     and constructive feedback on our own
                                                                                                                                                                                                                     work, for example by joining the CBD
                                                                                                                            are a strong incentive for us.               to cell biology. Together, we are a power   seminars and meetings.
                                                                                                Lucia Chavez-Gutierrez

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VIB-KU Leuven Center for Brain & Disease Research - Science & People 2018
CBD IN NUMBERS
      PIERRE: Overall, I believe together we               PIERRE: Our lab discovered a                 our research. After all, that is the final    together for dinner or drinks. On those
      will create a critical mass of groups                surprisingly simple way to make              goal of every biomedical researcher.          occasions, tradition dictates that every
      interested in complementary topics and               neurons of the cerebral cortex in a          We will always keep investing in clinical     new member in our team tells a
      technologies: the resulting synergy is               dish, using pluripotent stem cells. This     applications and in collaborations that       dirty joke.
      what I am hoping for, as it will create
      unique opportunities of new discoveries
                                                           started as a very exploratory project,
                                                           and results came out of the blue to
                                                                                                        help us work towards that goal.
                                                                                                        LUCIA: The same goes for me, I really
                                                                                                                                                      SHA: I would like to write a book about
                                                                                                                                                      the origin of all the Drosophila mutant
                                                                                                                                                                                                     ACCOMPLISHMENTS IN OUR FIRST YEAR AS CBD
      for everyone involved.                               us. I think it illustrates the importance    want to contribute to finding a cure          names. There are so many funny stories
                                                           of basic research for biotechnology          for Alzheimer’s disease. It might sound       behind these strange names. Maybe
      What are you most proud                              and medicine: we were initially driven       cliché, but it has been my motivation         I’ll do it when I retire? I also like to eat
      of professionally?                                   by our mere curiosity about neural           from the start – and I also think we can      weird food when I travel and have tried
                                                           development, but now pluripotent stem        do it. We will continue building on our       all kinds of meat. To other culinary
      THOMAS: Good question. I think our                   cell-based models of corticogenesis          current results but I also want to find       explorers I can recommend viper or
      group is well known for generating                   are used worldwide in academia and           other options, a plan B, C and D…             meat from a camel’s bump.
      better insights into temperature                     industry for brain disease modelling         PIERRE: I want to study the specificities     PIERRE: As for me, well when I’m not in
      sensing. We have become somewhat                     and drug discovery.                          of the human brain at the neuronal            the lab my main thrill is to sing in a rock

                                                                                                                                                                                                            127                           5
      of an international reference and that                                                            level, from genes to neural circuits, that    band. We are called the Fucking Come
      is something I am personally quite                                                                is our main goal. This is obviously a very    Back. Who knows, maybe we’ll come
      proud of. I am also very happy to see we                                                          challenging endeavour, but if successful,     over one day for a gig at a CBD party!
      have succeeded to attract talent, also                                                            it is likely to reveal exciting insights on
      from other departments in terms of
      collaboration. We have become a local                Together we will
                                                                                                        what makes us humans, whether in
                                                                                                        health or disease.
                                                                                                                                                      We’re already looking forward to it!
                                                                                                                                                                                                          PUBLICATIONS                NEW GROUPS
      hotspot for translational research.
      STEIN: I’m most proud of all the PhD
                                                           create a critical mass                       What should the rest of our center
      students that graduated in my lab and                of groups interested                         know about you or your team? Any
      continue enjoying scientific research.
      Research-wise, I’m proud of our
                                                           in complementary                             mottos, traditions or fun facts you
                                                                                                        would like to share?
      computational inventions that are used               topics and
                                                                                                        STEIN: That we are proud of our “humid
                                                           technologies
      world-wide by the community, such as
      iRegulon and SCENIC. Service-wise I’m                                                             lab”, based on three pillars: the wet-

                                                                                                                                                                                                              9                        306
      most proud of founding the Fly Cell Atlas                                                         lab, the computational lab, and the
      community and hosting its first meeting                                                           technology & microfluidics lab. That
      in Leuven, thanks to strong support of                                                            we are engaged towards open access
      the CBD.                                             Now that you have joined our center,         and open science. That hypothesis-
      SHA: My biggest contribution has been                what are your plans for the future?          free research is great fun. And that
      my Cell paper. Not because of the                                                                 computational thinking rules!                                                                 ERC GRANTS RUNNING             PEOPLE IN TOTAL
      journal it was published in, but because             STEIN: Our mission is to decipher the        PIERRE: People in our lab come from all
      of how it has challenged existing views              genomic regulatory code, and to exploit      over the world, from Japan to Linkebeek:
      on how sleep drive is generated in the               that knowledge to predict and modulate       this diversity is a lot of fun and a great
      brain. There are many papers of which                biological processes.                        strength as well.
      you could have predicted the outcome,                SHA: I’ll focus more of my lab’s effort      LUCIA: Hopefully people at our center
      that confirm what you or others already              on studying the function of sleep and        are aware of our strong expertise on
      thought, but this study generated a real             on defining sleep at the cellular level. I   kinetics and structure-function, and
      change in thinking, and I am                         have also come to realize that studying      maybe we can help out with some
      super proud of that.                                 the circuits one by one is maybe not         problems. Besides biochemistry, we
      LUCIA: I feel proud that I kept my drive             ideal. I would like to start using more      could also help with cocktails! Especially,
      and passion for science, while balancing             systematic approaches.                       but not limited to, piña colada.
      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.
                                                           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
                                                                                                        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
                                                                                                                                                                                                             17
                                                                                                                                                                                                         PHD DEFENSES
                                                                                                                                                                                                                                        38
                                                                                                                                                                                                                                     NATIONALITIES

CE NTER FO R BRA I N & DI S E AS E RE SE A R C H 2 0 1 8                                                                                                                                                                                               7
VIB-KU Leuven Center for Brain & Disease Research - Science & People 2018
RESEARCH GROUPS                                                                                                                    LOOKING BACK, MOVING FORWARD

                                                           STEIN AERTS                                                                 BART DE STROOPER
                                                           LABORATORY OF COMPUTATIONAL BIOLOGY                                         LABORATORY FOR THE RESEARCH OF
                                                           Our highlights of 2017 include the start of an ERC Consolidator Grant;      NEURODEGENERATIVE DISEASES
                                                           the publication of our new bioinformatics method SCENIC, which              After about 20 years of work and in collaboration with Lucia Chavez-
                                                           was quickly adopted by the community; our single-cell sequencing            Gutierrez, we have finally cracked the mystery how mutations in
                                                           of the entire adult fly brain that we accomplished in one year and          presenilin cause Alzheimer’s. We established a novel mouse/human
                                                           that lead to exciting collaborations with the Verstreken and Liu labs;      chimeric model for Alzheimer’s and got single cell sequencing up
                                                           our involvement in the Human Cell Atlas and our leading role in the         and working: ready to move into the study of the cellular phase of
                                                           foundation of the Fly Cell Atlas consortium.                                Alzheimer’s disease.
                                                           We look forward to more single-cell data, which will provide an             This year, we will provide the single cell analysis of the inflammatory
                                                           exciting foundation to discover new regulatory “recipes” of cell types,     component and the spatial transcriptomic profile of the full cellular
                                                           during development and aging. In our human research line we are             component of Alzheimer’s in a knock-in model for the disease. We
                                                           building a large “single-cell systems biology” resource of cancer cell      have been able to transplant human microglia in mouse brain and
                                                           state transitions. We are also creating new microfluidics solutions for     will now be able to establish the role of human microglia in the
                                                           single-cell migration studies and are exploring the possibilities           neurodegeneration of Alzheimer’s disease.
                                                           of organ-on-chip (tumoroid-on-chip).

                                                           WIM ANNAERT                                                                 JORIS DE WIT
                                                           LABORATORY FOR MEMBRANE TRAFFICKING                                         LABORATORY OF SYNAPSE BIOLOGY
                                                           We developed, with imec, magnetic nanoparticles that can be targeted        We uncovered new cell surface interactions regulating synaptic
                                                           to lysosomes and allow for their subsequent isolation. The high yield       identity and synaptic function in hippocampal circuits. A new
                                                           and purity permits lysosomal proteome and lipidome profiling and            challenge will be to start exploring how these mechanisms regulate
                                                           the identification of disease-related alterations in this key subcellular   connectivity, synaptic transmission and information processing in
                                                           compartment. Given that abnormalities in endo-lysosomal flux are            cortical circuits.
                                                           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.

                                                           LUCIA CHAVEZ-GUTIERREZ                                                      MARK FIERS
                                                           LABORATORY OF PROTEOLYTIC MECHANISMS MEDIATING                              BIOINFORMATICS EXPERTISE UNIT
                                                           NEURODEGENERATION                                                           Last year a number of successful collaborations on diverse topics
                                                           Our research substantially advanced our understanding of the                lead to great publications; a trend we hopefully will continue in the
                                                           mechanisms operating in familial Alzheimer’s disease and put                coming year. We aim to focus on the establishment of state of the art
                                                           forward a novel conceptual framework for the study of both familial         automated work flows and many diverse collaborations, with a focus
                                                           and sporadic forms of the disease. As next steps, we will depart from       on single cell and spatial transcriptomics.
                                                           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.

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VIB-KU Leuven Center for Brain & Disease Research - Science & People 2018
RESEARCH GROUPS                                                                                                                 LOOKING BACK, MOVING FORWARD

                                                           ROSE GOODCHILD                                                              ADRIAN LISTON
                                                           LABORATORY FOR DYSTONIA RESEARCH                                            TRANSLATIONAL IMMUNOLOGY LABORATORY
                                                           Last year we welcomed several new lab members in our growing                Last year we have made major advances in identifying and treating
                                                           team and published a pair of review articles on TOR1A-dystonia              primary immunodeficiencies. Through developing new mouse
                                                           and lipid synthesis. We also published the first results from a             models of these diseases and testing treatments already approved
                                                           long-running collaboration on striatal electrophysiogical defects in        for human use, we have been able to move straight to clinical trials.
                                                           dystonia mouse models. Overall, new data from several projects is           Over the next years we will get the clinical trial results back, and
                                                           continuing to point to abnormal lipid metabolism in TOR1A-dystonia.         hopefully will be able to make recommendations on changing the
                                                           We hope to start publishing these in 2018, as well as our research on       current therapeutic approach for these patients.
                                                           the mechanisms underlying a newly identified severe congenital form
                                                           of TOR1A disease.

                                                           NATALIA GUNKO                                                               SHA LIU
                                                           ELECTRON MICROSCOPY EXPERTISE UNIT                                          LABORATORY OF SLEEP AND SYNAPTIC PLASTICITY
                                                           Our highlights of 2017 include having a new “two-in one” combined light     For us, 2017 was a big year: the start of the lab and an ERC grant!
                                                           and electron imaging device (SECOM) installed and running, and Katlijn      We are excited that a pre-print of the first collaborative project with
                                                           Vints winning the image competition at the Crick Electron Microscopy        the CBD (the single cell atlas of the fly brain, with the groups of Stein
                                                           Opening symposium in London. We also co-authored 6 scientific               Aerts and Patrik Verstreken) is already out. This year, I look forward
                                                           papers. For this year, we are excited to do push things further using the   to expanding our team and our output as we explore the role and
                                                           new SECOM and with our new 3D imaging approaches, together with             mechanisms of sleep in the brain.
                                                           the light microscopy expertise unit.

                                                           MATTHEW HOLT                                                                SEBASTIAN MUNCK
                                                           LABORATORY OF GLIA BIOLOGY                                                  LIGHT MICROSCOPY EXPERTISE UNIT
                                                           Last year we made significant progress in understanding the degree          We are looking back on a prosperous 2017, where we reached out
                                                           of molecular heterogeneity between astrocytes in the CNS. This year,        to the community by organizing an Analysis Conference in Portugal
                                                           we hope to start investigating the functional consequences of this          (NEUBIAS), trained many students in our summer school and image
                                                           heterogeneity for CNS development and neuronal function.                    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.

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VIB-KU Leuven Center for Brain & Disease Research - Science & People 2018
RESEARCH GROUPS                                                                                                                   LOOKING BACK, MOVING FORWARD

                                                           DIETMAR SCHMUCKER                                                            PIERRE VANDERHAEGHEN
                                                           NEURONAL WIRING LABORATORY                                                   STEM CELL AND DEVELOPMENTAL NEUROBIOLOGY
                                                           In the continuous effort to elucidate basic mechanisms of neuronal           Last year was very fruitful for our ERC project: we identified a specific
                                                           wiring specificity my group excelled in 2017 and majorly advanced on         repertoire of more than 30 human-specific genes expressed during
                                                           all our projects. I am looking forward to help them to reap the benefits     human brain development, and now follow up on their functional
                                                           of their outstanding work in publishing important stories in 2018. This      characterization, which is already quite promising. For us, 2018 brings
                                                           includes work on CNS synapse formation, human/vertebrate DSCAM, a            a new start, as our lab joins the CBD. We are excited to intensify our
                                                           novel protein network controlling axon branching, evolution and function     existing collaborations within the center, for example on humanized
                                                           of protocadherin diversity, as well as our first work on axon regeneration   models for neurodegenerative diseases and on studying the
                                                           mechanisms. We are also looking forward to collaborating with the            temporal and spatial control of synaptic patterning.
                                                           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.

                                                           FREDERIC ROUSSEAU & JOOST SCHYMKOWITZ                                        PATRIK VERSTREKEN
                                                           SWITCH LAB                                                                   LABORATORY OF NEURONAL COMMUNICATION
                                                           The incorporation of Aelin Therapeutics is without a doubt the               We have made important discoveries that uncover how
                                                           biggest highlight of 2017 for our laboratory. In 2018 we look forward        neurodegenerative conditions, both pathogenic mutations in
                                                           to helping to make this company a success and to continue to                 Parkinson’s disease and tauopathies, affect synaptic cell biology.
                                                           develop the targeted aggregation platform that we created at the             We will now step up our efforts assess the functional consequences
                                                           Switch Laboratory. In particular, we have high hopes for novel               of these discoveries in vivo by starting to use mouse human brain
                                                           applications, such as in cancer or viral infections.                         chimera models as well as define the most vulnerable cell types
                                                                                                                                        in a living Drosophila brain using single cell RNA sequencing.

                                                           LUDO VAN DEN BOSCH                                                           THOMAS VOETS
                                                           LABORATORY OF NEUROBIOLOGY                                                   LABORATORY OF ION CHANNEL RESEARCH
                                                           Last year, we discovered that selective inhibition of histone                In 2017, we elucidated the molecular basis of noxious heat sensing,
                                                           deacetylase 6 (HDAC6) has a therapeutic effect on inherited as               by identifying the full set of heat sensors (all TRP channels!) that are
                                                           well as acquired neuropathies. Moreover, these inhibitors also               involved, and by developing a mouse model that is fully devoid of
                                                           reverse the axonal transport defects in motor neurons obtained               heat-induced pain. For 2018, we aim to specifically pinpoint where
                                                           from ALS patients. In 2018, we will further investigate the molecular        and when these channels become activated in vivo, and how they can
                                                           mechanisms responsible for the selective motor neuron death using            be specifically targeted to treat chronic pain. In addition, we foresee
                                                           motor neurons derived from induced pluripotent stem cells.                   important progress in the clinical translation of our research with the
                                                                                                                                        initiation of three clinical studies related to pain, bladder overactivity
                                                                                                                                        and diabetes.

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VIB-KU Leuven Center for Brain & Disease Research - Science & People 2018
TALKING 2017 RESEARCH
                                                                                                                                                                realized that the data we were collecting                states or regulators that were later                 easier to stay motivated when surrounded
                                                                                                                                                                was correlating with the age of onset of                 confirmed to be clinically relevant.                 by passionate scientists. We could rely on
                                                                                                                                                                the disease. I was running around the                    STEPHANIE: This work can be seen                     the expertise present at the center to help
                                                                                                                                                                lab searching for my supervisor to share                 as translational medicine, with direct               us mature our ideas, especially to push
                                                                                                                                                                the news. It gave us enormous energy to                  therapeutic benefit for the patients. Of             through during the revision process.
         Publishing an important discovery                        Can you summarize the significance             Why do you think the paper made it             keep on digging and understand what was                  course this is very rewarding. The fact
                                                                  of your findings for people outside            to such a good journal?                        really going on.                                         that we were able to better understand
       is hard work. Sara Aibar (postdoc in                       your field?                                                                                   STEPHANIE: When I started to work with                   the mechanism of the disease was also                Keep your eyes on the goal but most of
        the Aerts lab), Maria Szaruga (PhD                                                                       SARA: Although single-cell RNA-seq has         this model I already knew which gene was                 valuable to me.
                                                                                                                                                                                                                                                                              all enjoy the journey!
                                                                  SARA: We have developed a                      become a more broadly used method,             mutated (the one encoding the Artemis
      student in the Chavez-Gutierrez and                         computational method to infer the gene         and many researchers are interested in         protein). However, when I saw the mice                   How did the expertise (units) in our

          De Strooper labs) and Stephanie                         regulatory networks underlying the cell
                                                                  types present in a single-cell RNA-seq
                                                                                                                 learning about the regulatory mechanisms
                                                                                                                 in their systems, there were still no
                                                                                                                                                                for the first time I could tell that they were
                                                                                                                                                                developing the exact same symptoms
                                                                                                                                                                                                                         center make a difference for this story?             Do you have any advice for others?

           Humblet-Baron (postdoc in the                          dataset. This information provides a           analysis tools that exploited the higher       that we see in the clinic. I knew that other             SARA: Several groups started adopting                STEPHANIE: Always envision your

                    Liston lab) tell us about                     better understanding of the cell types or
                                                                  states, and highlights “master regulators”
                                                                                                                 resolution of scRNA-seq data to easily
                                                                                                                 address these questions. That’s why the
                                                                                                                                                                mouse models working on this gene had
                                                                                                                                                                never shown leaky SCID symptoms, so we
                                                                                                                                                                                                                         single-cell genomic methods in early
                                                                                                                                                                                                                         phases. Their experience and comments
                                                                                                                                                                                                                                                                              project as a story to write and tell. When
                                                                                                                                                                                                                                                                              you find a new result ask what would
                           their experience.                      that can be used as potential drug targets.    publication of our method was so timely.       needed to explore the model in depth.                    about the analysis of the data were very             be the next question and continue to
                                                                  MARIA: We have elucidated the                  MARIA: Getting the study into a journal        The other key moment was after treating                  useful when we were starting the project.            explore it further.
                                                                  pathogenic basis of Familial Alzheimer’s       with such a broad readership depended          our mice with the drug (CTLA4-Ig) – it                   In addition, although in the paper we only           MARIA: Keep your eyes on the goal
                                                                  disease caused by mutations in Presenilin,     heavily on the fact that we were answering     completely blocked disease, making this a                present the results on public data, the              but most of all enjoy the journey! The
                                                                  the catalytic core of the γ-secretase          one of the significant open questions in       very valuable project with new therapeutic               availability of in-house datasets to test            process of untangling complex questions
                                                                  protease, or in Amyloid Precursor Protein      the Alzheimer’s field and that it generated    opportunities for patients.                              and refine our method enabled us to get              and learning can be as rewarding as
                                                                  (APP), its substrate. Processing of APP by     insights that may hopefully guide future                                                                very relevant feedback.                              showing what you found to the world.
                                                                  Presenilin generates Aβ peptides, and we       drug discovery studies. The rest is            What are you personally most proud of?                   STEPHANIE: The FACS core was
                                                                  demonstrated that mutations destabilize        good timing.                                                                                            instrumental, as this project relied heavily         Aibar et al. Nature Methods 2017
                                                                  the γ-secretase-APP interactions and           STEPHANIE: We provide strong pre-              SARA: It is a very useful method! Many                   on this technique.                                   Humblet-Baron et al. J Allergy Clin Immunol 2017
                                                                  promote the ‘premature’ dissociation of        clinical evidence of drug efficiency to        people are interested in applying SCENIC                 MARIA: On a more general note, the                   Szaruga et al. Cell 2017
                                                                  the substrate thus generating longer,          treat a rare disease, directly proposing       to their own dataset, and in several                     whole community at our center made us
                                                                  more aggregation-prone Aβ peptides.            patient clinical trials. Since the treatment   studies it has already provided cellular                 feel supported and backed up. It is much
                                                                  Our results suggest that stabilizing the       is already approved for arthritis, it
                                                                  interactions between γ-secretase and           could be rapidly repurposed for leaky
                                                                  APP-derived substrates could become            SCID patients. In addition, our model is
                                                                  a therapeutic approach to tackle Aβ            available for further pre-clinical assays,
                                                                  production in Alzheimer’s disease.             including gene therapy.

                                                           We provide strong pre-clinical evidence of drug
                                                                                                                 When did you realize you were on to
                                                                                                                 something really interesting?
                                                                                                                                                                      RESEARCH OUTPUT IN NUMBERS
                                                                          efficiency to treat a rare disease

                                                                                                                                                                               127 = 2.54
                                                                                                                 SARA: The initial idea of the project
                                                                                                                 already sounded very interesting.
                                                                  STEPHANIE: Working in the field of             However, it wasn’t until we tested the full
                                                                  primary immunodeficiency disorders,            pipeline, and it recovered the relevant
                                                                  we described a new mouse model for             cell types plus some known regulators,
                                                                                                                                                                                publications in 2017                                publications per week
                                                                  severe combined immunodeficiency               that we confirmed it could actually work.
                                                                  (SCID), which recapitulates the key clinical   It was also very exciting when we saw
                                                                  features of SCID patients suffering of both    that our tool (SCENIC) was much better at
                                                                  immunodeficiency and autoimmunity              identifying cancer-related cell states than

                                                                                                                                                                               34%                                                  35%
                                                                  (leaky SCID). Importantly our model            regular clustering methods.
                                                                  proposed a novel efficient therapeutic         MARIA: Very early on, the feeling of
                                                                  approach for this disease.                     excitement surrounded us mostly because
                                                                                                                 we were answering a question that we
                                                                                                                 had all been extremely curious about.                          In top 5% of all journals in the field              In top 25% of all journals in the field
                                                                                                                 However, I still remember the day when I                       (Nature, Cell, eLife, Neuron, EMBO...)              (HMG, EMBO Reports, JBC, FASEB...)

CE NTER FO R BRA I N & DI S E AS E RE SE A R C H 2 0 1 8                                                                                                                                                                                                                                                                         15
VIB-KU Leuven Center for Brain & Disease Research - Science & People 2018
TECH TRANSFER

                                                           +                                        +
                1.3 M €
                     INDUSTRIAL
                                                                              5
                                                                  PATENT APPLICATIONS
                                                                                                                            1
                                                                                                                        SPIN-OFF
                   REVENUE IN 2017                                      IN 2017

                                                                                                                                                      Frederic Rousseau                                                                                                  Joost Schymkowitz

                 Truly innovative research leads to        We foster creative partnerships with         The risk-averseness of private investors
              the build-up of valuable intellectual        clinical and basic investigators at KU       and the poor reputation of investing in
       property, but whether it is the discovery           Leuven or other research centers.            the neurological disease field means
                of a new therapeutic target or the         We aim for long-term strategic               that forging partnerships is more             AELIN THERAPEUTICS
              development of a novel technology,           partnerships with the pharmaceutical         challenging than ever. That is why we         The research from the lab of Frederic Rousseau and Joost         for new antibiotics or in cancer treatment. The technology,
             bringing it to the clinic or industry is      industry with a mutual interest in           want to explore different, less traditional   Schymkowitz (Switch lab) is the foundation of VIB’s newest       branded Pept-ins™, harnesses the power of protein
          not always trivial. We constantly work           translating fundamental insights into        models of collaboration, through joint        and largest-ever spin-off company Aelin Therapeutics. The        aggregation to specifically induce the functional knockdown
          together with the Technology Transfer            hypotheses that can be tested in the         ventures, patient charity partnerships        team secured an investment of 27 million € to pioneer a novel    of a target protein.
        team at VIB, mainly through Floor Stam             clinic. We are convinced that target         and mixed models. We have also hired          modality in drug development to induce cell death, for example
                and Wim Grunewald, and with VIB            validation and drug discovery should         a ‘flying’ research technician, Alfonsa
       Discovery Sciences to make this happen.             be steered with deep mechanistic             Laragione, who will support translational
                                                           biology insights, especially in the          research projects at our center,
                                                           early stages.                                wherever opportunities arise.                 BACE1 TARGETING
                                                                                                                                                      BACE1 is one of the enzymes involved in the production           to develop new therapeutics for Alzheimer’s disease.
                                                                                                                                                      of amyloid-beta in Alzheimer’s disease. BACE1 antibodies         A biomarker test for BACE1 was also licensed to ADx
                                                                                                                                                      developed in the lab of Bart De Strooper were licensed to        and is currently being commercialized.
                                                                                                                                                      Denali, a San Francisco-based pharmaceutical company,

                                                                                                                                                      TECHNOLOGY DEVELOPMENT AND DRUG DISCOVERY
                                                                                                                                                      Our labs are a breeding ground for ideas and collaborations      cell biology. We are also developing partnerships for
                                                                                                                                                      with pharma partners. We are for example collaborating with      drug discovery and development projects, for example
                                                                                                                                                      industrial partners on single-cell sequencing and on synaptic    to identify gamma-secretase stabilizers and inhibitors.

      Floor Stam                                           Wim Grunewald                                Alfonsa Laragione

CE NTER FO R BRA I N & DI S E AS E RE SE A R C H 2 0 1 8                                                                                                                                                                                                                                     17
VIB-KU Leuven Center for Brain & Disease Research - Science & People 2018
Cupcakes for ‘Stichting
                                                                                                                                                                     Alzheimer Onderzoek”

                                                                            Bart De Strooper baking
                                                                            200 cupcakes                                                               Mendelcraft workshop at the Kids University

                                                                                                                                    Policy makers visit to
                                                                                                                                 discuss animal research

                                                                                                                                                                     Running at the
                                                                      News crew in our labs                                                                            Warmathon

                                                                                                      Princess Astrid visits
                                                                                                      the Voets lab

CE NTER FO R BRA I N & DI S E AS E RE SE A R C H 2 0 1 8
                                                           OUTREACH                                                            The Van Den Bosch lab at the
                                                                                                                               Amsterdam City Swim for ALS

                                                                                                                                                                                               19
SCIENTIFIC SUPPORT                                                                                                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,

      ASSOCIATION
                                                                                                                        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!

      The Scientific Support Association (SSA) is run by and for technicians

      GOALS                                                                                                             VIB POSTDOC COMMITTEE
      • Exchange know-how between labs                                                                                  Represents all postdocs and staff scientists at VIB CBD representatives:
      • Inform about expertise and services of the scientific                                                           Vinoy Vijayan (Verstreken lab) & Emanuela Pasciuto (Liston lab)
        facilities and units at our center                                                                              • Monthly networking in Brussels with postdoc representatives of
      • Build bridges between the center management and the                                                                different VIB Centers
        scientific support staff, including all lab managers and                                                        • Yearly postdoc day on career development
        lab technicians                                                                                                 • Stay up to date via facebook.com/VIBPostDocs
      • Have a positive impact on the research center and VIB
        by sharing ideas and solutions

      IMPLEMENTATION
      THE SSA ORGANIZES:
                                                                                            SSA                   PDA   CBD POSTDOC ASSOCIATION
      • Monthly meetings about a specific topic, ranging from safety                                                    Represents all postdocs and staff scientists at the CBD
        policy to new technologies                                                                                      President: Vinoy Vijayan (Verstreken lab) & Anupam Das
        - we invite speakers who share their expertise on innovative
           technologies such as single cell analysis, RNA Scope, CRISPR-
           Cas technology or electrophysiology.
                                                                               GET INVOLVED                             (Goodchild lab)

                                                                                                                        • Organization of Tuesday progress seminars and pizza lunch:
        - Speakers may also provide a basic introduction to specific           Meetings are every first Tuesday           Aleksandra Brajic (Liston lab), Luis Ribeira (de Wit lab) &
           topics such as statistics or first aid.                             of every month (unless indicated           Dan Dascenco (de Wit lab)
      • Discussions between scientific support staff about particular          differently) at noon in room             • Lunches with speakers of the Thursday distinguished
        experimental issues                                                    07.339.                                    lectures series:
      • Ad hoc working groups that can help putting new ideas and                                                         Emanuela Pasciuto (Liston lab) & Annerieke Sierksma
        initiatives into action                                                Get in touch with questions and            (De Strooper lab)
                                                                               suggestions or let us know if            • Coordination of the monthly happy hour:
      The SSA is also involved in the organization of the VIB seminar and      you want to join the organizing            Vinoy Vijayan (Verstreken lab)
      provides input for VIB trainings tailored to technical support staff,    committee: ssa@kuleuven.be.              • All CBD postdocs and staff scientists are automatically
      such as the VIB CRISPR User meeting that took place on Jan 31st,                                                    included on the postdoc mailinglist
      2017.

CE NTER FO R BRA I N & DI S E AS E RE SE A R C H 2 0 1 8                                                                                                                                                    21
THE ANNUAL PHD WEEK ORGANIZED BY THE VIB-KU LEUVEN
      CENTER FOR BRAIN & DISEASE RESEARCH AND NERF WAS
      ON TO ITS 6TH EDITION IN 2017.
      ACCORDING TO THE STUDENTS IT WAS AGAIN A
      TREMENDOUS SUCCESS!

                                                           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
CE NTER FO R BRA I N & DI S E AS E RE SE A R C H 2 0 1 8   sessions and company workshops.                                                                                                                        23
WHEN YOUR PHD IS FINISHED – WHAT COMES NEXT?
      It always seems impossible until it’s                                       developing an early biomarker for                                  Frightful, will I ever finish this project, get
      done. Once you have reached that                                            Parkinson’s disease and another in                                 it published and be able to graduate?
      milestone of obtaining your PhD,                                            which we develop a specific inhibitor                              I look back with a lot of appreciation
      how do you look back and what new                                           for Miro, since several Parkinson-                                 for my colleagues and for my mentors
      adventures await? We asked some of                                          related mutations impair Miro removal                              that enabled me to work in such an                                                     STEVEN: My friends, the great                                      science and social interaction. For                                    all of which have a high impact on
      our recent graduates.                                                       and delay mitochondrial degradation.                               excellent scientific environment. A                                                    atmosphere, the happy hours.                                       myself, I find basic research very                                     your PhD experience. What I think is
                                                                                  JOE: I have started a post-doc at Baylor                           scientific discovery is never made by one                                              ROELAND: Happy hours with the                                      interesting, but it can also be very                                   important is to always think one step
      Where do you work now and what                                              College of Medicine, researching                                   individual, it takes a hard working team.                                              Verstreken lab and others!                                         slow and frustrating. So I wanted to go                                ahead and not lose sight of the bigger
      do you do exactly?                                                          neurodegenerative diseases using                                   JOE: My PhD was challenging but very                                                   JOE: The state-of-the-art equipment,                               for more applied science. Having the                                   picture. Try to involve as many people
                                                                                  large screening platforms and mouse                                rewarding. It was a time of a lot of                                                   and the many networking events.                                    sales aspect in my job was actually not                                as possible in your research. Try to
      HERMIEN: I am a product specialist                                          models of disease.                                                 personal and professional growth.                                                                                                                         planned, but I like to try new things.                                 develop your soft skills: defining the
      at Biognost. We distribute products,                                        WENTING: I am working as a                                         ISABEL: Even when the PhD could look                                                   What do you like most about your                                   Another factor was the location, as I was                              problem (this is sometimes already
      mainly in the field of autoimmunity                                         postdoctoral researcher at CBD as well                             at some point very frustrating and you                                                 new job?                                                           looking for a job close to home.                                       half of the work), explaining the science
      and infectious serology. Our                                                as the stem cell institute at KU Leuven.                           may feel that you are stuck without                                                                                                                       STEVEN: Because of the exciting                                        (also to non-experts), making other
      customers are hospital labs, private                                        ISABEL: I’m currently still in the CBD                             doing or learning anything new; once                                                   HERMIEN: I meet a lot of people, with                              research environment.                                                  people enthusiastic about your work,
      labs, but also contract research                                            but looking for post-docs abroad.                                  you start talking with people from other                                               all kinds of different jobs. I like making                         ROELAND: Deciding what to do after my                                  building your network… These skills are
      organizations. My job is to give                                            Preferably in a different field to be                              fields or institutes you realized how                                                  and giving presentations, teaching                                 PhD was not easy. At the SfN meeting                                   important in every job!
      presentations and workshops, to train                                       able to learn different approaches and                             much experience you actually acquired.                                                 people and this is also an important                               in San Diego, I talked with Xinnan                                     LAURA: My advice to other PhD
      people how to work with our products,                                       points of views.                                                   Something I took for granted when I                                                    part of my job. My colleagues are also                             Wang, and she invited me to her lab                                    students is to exploit the many
      and to maintain a good relationship                                                                                                            was in the lab!                                                                        very nice.                                                         at Stanford to present my work. We                                     opportunities at VIB and KU Leuven to
      with our customers. Next to the                                             How do you look back on your PhD                                   WENTING: It was an exhausting but also                                                 LAURA: What I like of this job is the                              continued discussions over the following                               strengthen not just your scientific but
      general portfolio, my specialty within                                      experience?                                                        fruitful process. I gained a lot of new                                                possibility to exploit my scientific                               months, and since I am very interested                                 also your soft skills. Those will be useful
      the company is neurodegeneration,                                                                                                              knowledge in science and technology                                                    background and build up new                                        in translational research, we worked                                   later on, whatever you decide to do.
      which is still quite new.                                                   HERMIEN: With a smile! Knowing what                                and also developed my soft skills. As                                                  knowledge in the patent law field. Plus,                           out an exciting project, where I am able                               STEVEN: I would say, don’t stress out too
      LAURA: I am currently working for                                           I know now, I would definitely do it                               a complete foreigner, I had to adapt                                                   working for a pharma company is very                               to collaborate with companies but still                                much, it will work out.
      a pharma company in Switzerland.                                            again. The people I met and the skills I                           to a completely new environment and                                                    exciting.                                                          develop my own ideas.                                                  ROELAND: My advice would be to
      I entered the intellectual property                                         developed were important for shaping                               culture and made some good friends                                                     STEVEN: The absolute freedom I get to                              JOE: They are leaders in their field                                   define what your passion is and look for
      field, my aim is to become a European                                       me into who I am now.                                              from totally different backgrounds. All                                                pursue whatever I think is interesting,                            and experts in research areas and                                      opportunities that are out there that can
      patent attorney. This requires a                                            LAURA: I think the PhD was a very                                  of these enriched my life and enhanced                                                 and the extremely collaborative                                    techniques that compliment my                                          help you get there. Importantly, you will
      training period (which is what I am                                         interesting experience, definitely                                 my career.                                                                             environment.                                                       research interests.                                                    need to take action, don’t just wait until
      doing now) and to pass exams for the                                        helpful for the next professional steps.                                                                                                                  JOE: The fact that it builds upon the                                                                                                     opportunities come to you, create your
      qualification.                                                              STEVEN: I am very satisfied. I think I                             Is there something you already miss                                                    skills from my PhD to further develop                              Any advice for other PhD students?                                     own.
      STEVEN: I started a postdoc at                                              got the most out of it.                                            about the CBD?                                                                         my long-term research goals                                                                                                               JOE: Stay motivated and focused. In the
      Stanford University in the lab of Aaron                                     ROELAND: My time as a PhD-student                                                                                                                                                                                            HERMIEN: This is a difficult question,                                 end, things always work if you do.
      Gitler.                                                                     was both exciting and frightful.                                   HERMIEN: The international                                                             Why did you choose that job,                                       as the experience of doing a PhD is
      ROELAND: I also work at Stanford                                            Exciting, learning how to handle a                                 environment, the enthusiasm about                                                      company or lab?                                                    different for everyone. I was quite lucky
      University, in the lab of Xinnan                                            project, trying out new techniques,                                science, the good mix of scientific                                                    HERMIEN: A combination of reasons:                                 with my project, my supervisors, the
      Wang. I work on two projects: one on                                        discussing and troubleshooting, etc.                               discussions and healthy gossip…                                                        I was looking for a job that combines                              colleagues and the available equipment,

                CALLAERTS LAB CALLAERTS LAB
                      (CENTEROF
      (CENTER FOR THE BIOLOGY FORDISEASE)
                                   THE BIOLOGY OF DISEASE)            DE STROOPER LAB DE STROOPER LAB                                VAN DEN BOSCH LAB
                                                                                                                      VAN DEN BOSCH LAB                                             VAN DEN BOSCH LAB
                                                                                                                                                                     VAN DEN BOSCH LAB                               VERSTREKEN LAB VERSTREKEN LAB                     VERSTREKEN LAB VERSTREKEN LAB                 VAN DEN BOSCH LAB
                                                                                                                                                                                                                                                                                                                                    VAN DEN BOSCH LAB         CHAVEZ-GUTIERREZCHAVEZ-GUTIERREZ
                                                                                                                                                                                                                                                                                                                                                                                AND DE STROOPERAND
                                                                                                                                                                                                                                                                                                                                                                                                LABSDE STROOPER LABS           DE STROOPER LAB DE STROOPER LAB

                  10/01/2017      10/01/2017 16/01/2017      16/01/2017 23/01/2017      23/01/2017 26/01/2017   26/01/201704/05/2017    04/05/201718/05/2017  18/05/201723/05/2017    23/05/2017 24/05/2017 24/05/201709/06/2017 09/06/201714/06/2017         14/06/2017 01/09/2017     01/09/201702/10/2017   02/10/201704/10/2017    04/10/201709/10/2017       09/10/2017 20/10/2017     20/10/201709/11/2017       09/11/2017 01/12/2017    01/12/2017
                   MARIJKE         MARIJKE SIMON               SIMON HERMIEN             HERMIEN LAURA            LAURA STEVEN            STEVEN LALEH           LALEH     ANKE          ANKE      LADAN      LADAN ROELAND       ROELAND DEAN                   DEAN      JOSPEH         JOSPEH MIRIAN         MIRIAN WENTING          WENTING SANDER             SANDER SARAH               SARAH EMRE                 EMRE ISABEL              ISABEL
                  VERSTEVEN       VERSTEVENWEINBERGER        WEINBERGER ACX                ACX PAPARELLI         PAPARELLI BOEYNAEMS    BOEYNAEMSKHODAPARAST KHODAPARASTWOUTERS        WOUTERS KHODAPARAST KHODAPARAST
                                                                                                                                                                                                                   VANHAUWAERT VANHAUWAERTFRANCKAERT          FRANCKAERT MCINNES         MCINNES SAIZ RUBIO    SAIZ RUBIO GUO             GUO       BEEL             BEEL VEUGELEN           VEUGELEN ETLIOGLU          ETLIOGLU SALAS             SALAS

                                            HASSAN LAB HASSAN LAB                          ANNAERT AND MUNCK
                                                                                                         ANNAERT
                                                                                                             LABSAND MUNCK LABS                    SWITCH LAB   SWITCH LAB                       SWITCH LAB   SWITCH LAB                         LISTON LAB    LISTON LAB                         SWITCH LAB   SWITCH LAB                    VAN DEN BOSCH LAB
                                                                                                                                                                                                                                                                                                                                                            VAN DEN BOSCH LAB                       SCHMUCKER LAB SCHMUCKER LAB
                                 (CENTER FOR THE BIOLOGY
                                                 (CENTEROF
                                                         FORDISEASE)
                                                              THE BIOLOGY OF DISEASE)
CE NTER FO R BRA I N & DI S E AS E RE SE A R C H 2 0 1 8                                                                                                                                                                                                                                                                                                                                                                                                     25
SINGLE CELL AND MICROFLUIDICS
                                                                                                           Suresh Poovathingal
                                                                                                                                                               THE FACS CORE IS GROWING
                                                                                                                                                      VIB is investing in a FACS Core facility, with a site      Christèle Nkama is a technician at the core and
                                                                                                                                                      in Leuven and a site in Ghent. On January 1st, the         Matthew Holt and Susan Schlenner are on the user
                                                                                                                                                      existing Leuven FACS Core became the VIB-KU Leuven         committee.
                                                                                                            Have you met Suresh                       FACS Core, jointly hosted by the Center for Cancer         Thanks to some exciting recent and upcoming
                                                                                                            Poovathingal? He joined the CBD           Biology and the Center for Brain & Disease Research.       investments, the core continues to grow. These new
                                                                                                            in 2017 to lead our newest single         Adrian Liston remains the core’s director and Pier         investments make the FACS core the best-equipped
                                                                                                            cell expertise unit.                      Andrée Penttila the core manager. From our Center,         one in Belgium, and one of the very top in Europe!

      What is your background and how did                  What do you like about this new               In terms of equipment, what are you
      you end up as our single-cell analytics              challenge of starting up the expertise        hoping to add?
      and microfluidics expert?                            unit at our center?
                                                                                                         From my experience, we are well
      I’m a chemical engineer by training and              I’m interested in technology                  equipped. The core has access to a
      did my PhD in computational biology.                 development and this is exactly what          broad range of tools, either via VIB
      My PhD focused on mitochondrial                      I like about my new position here.            or KU Leuven. VIB’s tech watch also
      biogenesis and the role of mitochondrial             Our single cell expertise unit is not         helps us get access to some of the key
      genome drift in aging and degenerative               just about servicing, we also want to         emerging technologies on the market.
      diseases. It is intriguing to observe a              develop new methods. Together with            Single cell analytics is a new field and
      mosaic pattern of mitochondrial DNA
      mutations in seemingly homogeneous
      tissue. Some cells have a high load of
                                                           the group of Stein Aerts, we are trying
                                                           to develop novel assays for single
                                                           cell transcriptome, epigenome and
                                                                                                         many technologies are still under
                                                                                                         development. What I want for next year
                                                                                                         doesn’t exist yet. We hope to develop
                                                                                                                                                      NEW INVESTMENTS IN 2017
      mutations, whereas the neighboring ones              proteome profiling based on droplet/          some of these technologies ourselves!        BD Symphony, a 5-laser/28-color flow cytometry             Amnis ImageStream, which combines the analysis
      don’t. My project took computational                 nanowell platforms. If you have a related     Spatial transcriptomics is something         analyzer, currently the most powerful analyzer on the      of flow cytometry and microscopy into one machine;
      approaches using stochastic modeling                 research problem, we can always discuss       that we want to set up soon, with            market, and the only one in an academic setting in         acquired via a KU Leuven small and medium equipment
      techniques to understand the origin of               it, even if it means developing new           funding from a Hercules grant. Single        Belgium; acquired via a Hercules grant (promoter Adrian    grant (promoter Adrian Liston, co-promoters include
      this heterogeneity.                                  methods.                                      cell proteomics is another technique         Liston, co-promoters include Matthew Holt and Bart De      Wim Annaert)
      That project was the beginning of my                                                               I am hoping to add. Oligo-tagged             Strooper)
      single cell interest and it also made                You also collaborate a lot with Mark          antibodies are a powerful tool for
      me realize the importance of bridging                Fiers who leads our bioinformatics            protein quantification and we hope to        BD Influx, for Index sorting; equipped with 4 lasers and   FACS Melody, Cancer foundation grant (promoter
      the computational and experimental                   platform.                                     integrate this with droplet-based assays     16 colors, housed under a BSL2 biosafety cabinet to sort   Thierry Voet (KU Leuven), co-promoters include
      domains. I wanted to explore and                                                                   to increase the throughput of single cell    infectious and human samples; acquired via the same        Stein Aerts)
      develop my wet-lab skills. It can be                 Yes, of course. Our projects inherently       proteome profiling.                          Hercules grant
      difficult to switch so radically, but I got          have high computational requirements,
      this opportunity during my postdoc. As               so before actually starting the               You have big plans! How busy are
      part of a knowledge transfer fellowship
      offered by Luxembourg, I had a chance
      to work in a lab at Caltech focusing on
                                                           experiments, I encourage you to discuss
                                                           the bioinformatics with Mark Fiers and
                                                           Stein Aerts. Our analysis pipeline goes
                                                                                                         things at the single cell unit?

                                                                                                         Quite busy, actually! There are several
                                                                                                                                                      NEW INVESTMENTS IN 2018
      single cell proteomics using microfluidics           from the experimental design to sample        collaborative and developmental              • Immunology screening platform available through Stephanie Humblet-Baron (Liston lab)
      technology. The idea of the fellowship               preparation, single cell analysis and         projects underway at the single cell core.   • New equipment from the Center for Cancer Biology is being integrated (AriaIII and Verse)
      was to bring the expertise to Luxembourg             library processing. What comes after –        If you or your team have any questions       • We hope to acquire a CyTOF via a new Hercules grant (promoter Frederik De Smet (KU Leuven), co-promoters
      to set up a single cell analysis facility in a       data analysis and interpretation – is a big   requiring a single cell approach, just get     include Adrian Liston, Matthew Holt, Bart De Strooper and Joost Schymkowitz)
      research institute focusing primarily on             endeavor!                                     in touch with me.
      Parkinson’s disease. When I learned about
      this position, setting up a single cell facility
      at CBD in Leuven, I applied immediately.

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STUDENTS HUNGRY FOR MORE
                                                                                                                                                    Ben Verpoort and Hannah Walgrave joined the CBD community as MSc students, working on their thesis project in the labs of
                                                                                                                                                    Joris de Wit and Bart De Strooper, respectively. Dries T’Syen did his BSc thesis project in the De Strooper lab as well. One year
                                                                                                                                                    later, all three received awards for their work and stayed with us for their next adventure: a PhD or a technician job.
                                                                                                                                                    How did they catch the bug for research and why did they stick around?

                                                                                                                                                    What was your project about?                     of the disease. That’s why we wanted to       job at our center? The work, the topic,
                                                                                                                                                                                                     explore whether it had the same effects in    the colleagues, or all of the above?
                                                                                                                                                    BEN: In the Laboratory of Synapse Biology        late stages, and if so, whether that might
                                                                                                                                                    (de Wit lab), we focus on the role of            lead to potential therapeutic applications,   DRIES: All of the above! There is still a lot
      BIOINFORMATICS                                       BIOPHYSICS                                   ELECTRON MICROSCOPY                         synaptic cell adhesion molecules in the          for example using Hannah’s approach.          to be learned in the field of neuroscience

      MARK FIERS                                           FREDERIC ROUSSEAU & JOOST                    NATALIA GUNKO                               development of neural connectivity. Cell
                                                                                                                                                    adhesion molecules are cleft-spanning            You were all selected as awardees for
                                                                                                                                                                                                                                                   so it is an exciting field to work in. With a
                                                                                                                                                                                                                                                   broad range of new topics and challenges,
      The bioinformatics platform focuses                  SCHYMKOWITZ                                  The electron microscopy platform fa-
                                                                                                                                                    proteins that engage in trans-synaptic           different prizes. Why do you think your       I’ll have the opportunity to learn new
      on the data analysis and interpre-                   This collaborative technology platform       cilitates ultrastructural imaging of bio-
                                                                                                                                                    complex formation to orchestrate various         work was so well received?                    techniques like CRISPR/Cas to help move
      tation of sequence data, specifically                provides biophysical and structural          logical samples and provides individual
                                                                                                                                                    aspects of synaptogenesis, i.e. the                                                            the research projects in our lab forward.
      spatial and single-cell transcriptom-                insight into biological phenomena            training in scanning and transmission
                                                                                                                                                    formation of new synapses. During my             BEN: I believe I got the award because of     HANNAH: The decision to stay on for
      ics, at different stages of pathology.               that are driven by protein folding,          electron microscopy and in sample
                                                                                                                                                    thesis, I tried to elucidate the intracellular   the quality and quantity of the work that     a PhD was based on a combination of
      The expertise ranges from exper-                     aggregation and interactions. Expertise      preparation. The platform provides
                                                                                                                                                    trafficking itinerary that governs axonal        I was able to present. I talked to a few      factors. For one, I really liked the people
      imental design to data analysis                      spans from structural bioinformatics         expertise in conventional scanning
                                                                                                                                                    targeting of neurexin, perhaps the most          professors that were part of the selection    in the lab and especially the collaboration
      for genomics, transcriptomics and                    to molecular biophysics, including           and transmission electron microscopy,
                                                                                                                                                    well-known cell adhesion molecule. In            committee, each of them complemented          with my supervisor Evgenia Salta. In
      single-cell approaches.                              protein purification, in silico modelling,   immunocytochemistry and advanced
                                                                                                                                                    view of the major role that neurexin plays       me for my writing skills, for which I am      addition, I could continue the work on
                                                           and studying protein conformation,           3D methods, and provides tailored
                                                                                                                                                    in brain function, a better understanding        very grateful.                                the same project of my master thesis
                                                           structure and interactions.                  solutions for the different research
                                                                                                                                                    of how this key synaptic organizer reaches       HANNAH: I think I got the prize because       that I enjoyed working on. And finally, the
                                                                                                        lines and projects at our center.
                                                                                                                                                    its site of action is crucial.                   it was a nice, well-designed project for      opportunity to pursue a PhD in a very well
                                                                                                                                                    HANNAH: My project consisted of                  a master student. The goal was very           established and big lab, that provides all
                                                                                                                                                    finding a clinically relevant way to get         clear and achievable during the period        possible opportunities, was an important
                                                                                                                                                    microRNA-132 into the brain, in a mouse          I was in the lab, using several different     factor as well.
                                                                                                                                                    model for Alzheimer’s, and to evaluate           techniques. Also, the trouble shooting        BEN: I decided to stay because of the very
                                                                                                                                                    if this has any beneficial effects on the        during the optimization made sense and        positive experience I had during those
                                                                                                                                                    disease progression. After several trials,       contributed to the learning process.          9 months of intense research. Great
                                                                                                                                                    I was able to overexpress this microRNA          DRIES: I think it is a combination of         mentorship, both from my supervisor
                                                                                                                                                    in the hippocampus using intranasal              several factors. For starters, the project    Luis Ribeiro and our group leader Joris de
                                                                                                                                                    delivery. This overexpression caused             itself and Alzheimer research more            Wit, certainly played an important role in
                                                                                                                                                    some changes in amyloid β levels and             generally are timely in light of the          successfully finishing and defending my
                                                                                                                                                    tau phosphorylation, the two major               pressing societal challenges of dementia.     thesis work. Moreover, because of the
      ELECTROPHYSIOLOGY                                    LIGHT MICROSCOPY                             MUTAMOUSE                                   pathological hallmarks of the disease.           Next, the goal of my internship was to        cutting-edge technologies available in

      KEIMPE WIERDA                                        SEBASTIAN MUNCK                              SUSAN SCHLENNER, ADRIAN                     DRIES: I also looked at miR-132, more
                                                                                                                                                    specifically at the effect of increasing its
                                                                                                                                                                                                     learn a wide variety of techniques and
                                                                                                                                                                                                     incorporate all the obtained data into a
                                                                                                                                                                                                                                                   this institute and thanks to the support of
                                                                                                                                                                                                                                                   several expertise units, I believe that the
      The electrophysiology platform                       Our light microscopy platform is
                                                                                                        LISTON & LUTGARDE SERNEELS                  levels in old mice representing a late-          fitting story. The lab helped me a lot with   VIB-KU Leuven Center for Brain & Disease
      provides expertise and access to                     part of the VIB Bio Imaging Core,            MutaMouse is a VIB-KU Leuven                stage model for Alzheimer’s disease. Our         achieving those goals.                        Research will grow to be at the forefront
      state-of-the-art electrophysiology                   a dual site facility at Ghent and            core facility that provides a range         lab and others already demonstrated that                                                       of neuroscience research in Europe. So,
      systems. The platform assists                        Leuven. The platform provides the            of mouse genetics services from             increasing the levels of this micro RNA          What in particular convinced you to           the question is: why wouldn’t I stay?
      with the formulation, design and                     expertise and infrastructure for             model creation to embryology,               in young mice improves several aspects           stay and pursue a PhD or a technician
      execution of electrophysiological                    cutting-edge imaging and aims to             including CRISPR/Cas9 genome
      experiments to resolve the                           foster collaborations across our             editing, mouse/embryo production
      functional physiological aspects of                  center. Support ranges from macro            (zygote, blastocyst injections),
      ongoing research projects. Training                  to super-resolution microscopy and           cryopreservation and cryorecovery
      and support is also organized for                    the development of novel schemes             (sperm/embryo and IVF), embryo
      individual researchers, allowing                     for image analysis.                          rederivation, as well as rapid colony
      them to conduct experiments                                                                       development, line rescue and speed
      independently.                                                                                    backcrossing.

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