2018 DANDRITE ANNUAL REPORT 2018 DANDRITE ANNUAL REPORT Words from the Director 01 3 Organization Structure Organization Structure Hosting Departments Executive Board Management Steering Committee Monthly Extended Steering Committee Meeting Monthly Coordination Meeting Administrative Support Team Technician Network Young DANDRITE The Ph WORDS FROM THE DIRECTOR 3 Words from the Director It is with great pleasure I welcome you to our 2018 annual report from DANDRITE the Danish Research Institute of Translational Neuroscience funded by the Lundbeck Foundation, and at the same time the Danish node of the Nordic EMBL Partnership for 4 ORGANIZATION STRUCTURE 01 Organization Structure ORGANIZATION STRUCTURE 5 6 ORGANIZATION STRUCTURE Organization Structure EXECUTIVE BOARD DIRECTOR EMBL Partners Scientific Advisory Board STEERING GROUP COMMITTEE ADMINISTRATIVE SUPPORT GROUP LEADERS Poul Nissen Structural Biology Anders Nykjær Receptor Biology Poul Henning Jensen Neurodegenerative Diseases CORE ORGANIZATION STRUCTURE Hosting Departments DANDRITEs executive hosting institution is Aarhus University and with neuroscience research being an innately interdisciplinary endeavor DANDRITE is placed as an Interfaculty center at the university and hosted fruitfully by the two departments: Departmen 8 Executive Board Chair: Clinical Professor Jens Chr. Hedemann Sørensen, Department of Clinical Medicine, Aarhus University (chair from December 2016) Professor Poul Henning Jensen, DANDRITE Dean Niels Christian Nielsen, The Faculty of Science and Technology (from February 2019, Dean Lars Henrik 9 Management STEERING COMMITTEE The steering committee meets every Monday at 10-11 AM and consists of the director, the core group leaders and two representatives of the group leaders (internally elected for two-year terms). DANDRITEs administrative personnel also attends the meetings. The steerin 10 ORGANIZATION STRUCTURE ADMINISTRATIVE SUPPORT TEAMS TASK-MATRIX Who to contact? Subject Maria T. Jensen Karen Bech-Pedersen Susanne S. Sjøgaard Research Group support Group support: Nabavi, von Philipsborn, Kvitsiani, Yonehara, Denham, Jensen, and Takeuchi Group support: Nissen, Pou ORGANIZATION STRUCTURE DANRITE Christmas get-together 2018 with many of the true young DANDRITEs having a blast with our very own Santa (postdoc Michael Clausen) Young DANDRITE The PhD & Postdoc association at DANDRITE The PhD & Postdoc Association at DANDRITE, Young DANDRITE (recently renamed t 12 ORGANIZATION STRUCTURE Scientific Advisory Board The scientific advisory board convenes biannually and provides independent advice on scientific and strategic matters, and evaluations of achievements, ideas and strategies. SAB members are international, highly reputed researchers. The third DA ORGANIZATION STRUCTURE 13 DANDRITE Affiliated Researchers DANDRITE is proud to enter year 2019 with ten active Affiliated Researchers: JØRGEN KJEMS Nanomedicine The Kjems lab investigates the function and biomarker potential of non-coding RNA in brain and peripheral nervous system. In particular, 14 Former PhD student Toke Jost Isaksen receives Aarhus University Research Foundation PhD Award. Using mice tests Isaksen has localised a defect in the sodium-potassium pump found in brain cells. The discovery may affect future treatment of neurological disorders.... MORTEN SCHALLBURG NIELSEN Rec 15 ically modified SORL1 pig as a model of Alzheimers disease (EP Application No. 18199331.2; TECH-2018-631-120) THOMAS BOESEN Cryo-EM on membrane transporters and receptors I am involved in research projects centered on nanodisc technology and structural biology of membrane protein transporters an 16 RESEARCH ACTIVITIES 02 Research Activities RESEARCH ACTIVITIES 17 18 RESEARCH ACTIVITIES Nissen Group Structural and Functional Studies of Membrane Transporters in Brain Professor Poul Nissen The Nissen lab investigates molecular mechanisms of membrane transport processes and higher-order structures of neuronal membranes. Activities are mainly focused on cryo RESEARCH ACTIVITIES Figure 1: Schematic diagram showing a mechanism of action of dimethyl fumarate (DMF in yellow), a potent drug used in the treatment of multiple sclerosis and psoriasis. A high-resolution crystal structure revealed the binding site of DMF on the RSK2 kinase, where it forms a cova 20 RESEARCH ACTIVITIES Jensen Group Neurodegenerative Disease The Jensen group is studying how α-synuclein contributes to the neurodegenerative processes in Parkinsons disease, Lewy body dementia and multiple systems atrophy, which are hallmarked by prion-like spreading of intracellular aggregate RESEARCH ACTIVITIES Jensen group members at the project day when Denmark played 1:1 against Australia in the World Cup. Photo by PH Jensen Selected highligts 2018 A decreased cytosolic calcium concentration as an early decisive effect of cellular α-synuclein aggregate stress due to SERCA calcium p 22 RESEARCH ACTIVITIES Nykjær Group Receptor Biology Research activities of the Nykjær Group are focused towards the functional characterization of a family of neuronal type-1 receptors denoted Vps10p-domain receptors or sortilins. Members of this gene family, which comprises sortilin, SorCS1, S RESEARCH ACTIVITIES 23 In situ hybridization of a receptor in sections of embryonic mouse brain. Specific brain regions are indicated. Illustration by Peter Lund Ovesen Pallium/Cortex LGE MGE HIP Nykjaer group members Photo by Else Magård Selected highligts 2018 In 2018, the Center of Excellen 24 RESEARCH ACTIVITIES Denham Group Stem Cells Group Leader Mark Denham We study how the human nervous system develops and the processes involved in neurodegeneration. To do this, we use human pluripotent stem cells, which have the unique ability to give rise to all cell types of the body, and RESEARCH ACTIVITIES 25 Fig 1: (A) 30 day sendai virus reprogramming protocol used to convert human patient fibroblast cells into induced pluripotent stem cells in defined media. (B) Image shows human fibroblast cells prior to reprogramming, (C) and right image shows a successfully reprogrammed iPS 26 RESEARCH ACTIVITIES Kvitsiani Group Neuronal basis of decision-making in fruit flies and mice We investigate genetic and neural circuit mechanisms of foraging decisions. The methods we use include molecular genetics, psychophysics, behavioral electrophysiology, optogenetics and computational m RESEARCH ACTIVITIES 27 Fig. 2: Generating focus using the SLM- spatial light modulator and CCD camera. Left panel, schematics of experimental setup consisting of laser, ISO-otical isolator, GTP-light polarizer, M-mirror, L lenses for beam expansion, SLM, PH-pinhole, Objective- focusing light onto 28 RESEARCH ACTIVITIES Nabavi Group Circuit mechanisms of learning and memory Group Leader Sadegh Nabavi Synaptic plasticity remains an (almost) indisputable candidate for learning and memory. For this reason, a large body of works is devoted to the mechanisms underlying plasticity; with the ma 29 RESEARCH ACTIVITIES # of cells in 106um 3 AON AON *** 0.5 0.4 0.3 0.2 0.1 # of cells in 106um 3 0.4 T AON AON *** 0.5 Control TM PB S 0.0 20x AON 20 Figure 2. Exposure to an innately avers ity-dependent tracing from the cortica 0.3 retrograde labeling shows anterior olfa acti 30 RESEARCH ACTIVITIES Philipsborn Group Behavioral Genetics and Circuit Neuroscience We are interested in how the nervous system generates and controls behavior- at the level of genes and molecules, cells and neuronal circuits. Our model system is Drosophila melanogaster, which has a relatively RESEARCH ACTIVITIES 31 Philipsborn group members in the old library. Photo by Maria Thykær Jensen, DANDRITE sequence. We discovered that dependent on the state of the animal and the behavior it is engaged in, activation of neuronal classes has drastically different motor outcomes. By using optoge 32 RESEARCH ACTIVITIES Yonehara Group Spatially Asymmetric Neural Circuits in Visual System The Yonehara group investigates how spatial asymmetry in the neuronal circuits arises during development and support neural computation in adults using mouse visual system as a model. Team Leader Keisuke RESEARCH ACTIVITIES Yonehara lab photo taken August 2018. Photo by Szilard Sajgo. MOLECULAR MECHANISMS UNDERLYING THE SPATIALLY ASYMMETRIC NEURONAL CONNECTIVITY Spatially asymmetric neuronal connectivity is the fundamental building block of neuronal computation. We use retinal direction-selective 34 RESEARCH ACTIVITIES Kjærgaard Team Synaptic Plasticity and Intra-cellular Signaling Complexes in Memory Formation Team Leader Magnus Kjærgaard We are interested in understanding how proteins in the post-synaptic density modulate the dynamics of synaptic proteins and signalling pathways. We s RESEARCH ACTIVITIES Fig 1: Liquid-liquid phase separation by synaptic scaffolding proteins. Picture by: Postdoc Xavier Warnet Kjærgaard team members on stairs in lab building. Photo by Karen Bech-Pedersen 35 36 RESEARCH ACTIVITIES Poulsen Team Electrophysiology of Electrogenic Transporters and Ion Channels We study membrane proteins important for neuronal signaling and transport in order to understand their basic mechanisms and the pathophysiological consequences it has if they do not function optima RESEARCH ACTIVITIES 37 Fig 1: Structural context of S779. Left: An overview of the Na,K-ATPase with the alpha subunit in grey, the beta subunit in blue and the gamma subunit in red. The two potassium ions are yellow spheres, S779 is in orange stick, and the ion-coordinating transmembrane helices a 38 Takeuchi Team Memory selectivity and knowledge updating Team Leader Tomonori Takeuchi Knowledge plays a central role in human life. Indeed, we are who we are largely because of what we learn and what we remember. Our knowledge structure (called schema) consists of our past experiences and fac 39 Figure 1: An event arena in rats. Photo by Tomonori Takeuchi). Figure 2: Takeuchi team members. Photo by Kim Henningsen). Publications 2018 Duszkiewicz AJ, McNamara CG, Takeuchi T, Genzel L (2018) Novelty and Dopaminergic Modulation of Memory Persistence: A Tale of Two Systems. Trends in Neuro 40 EVENTS, VISITORS, GUESTS & SEMINARS 03 01 Events, Visitors, Events, Visitors, Guests & Seminars Seminars EVENTS, VISITORS, GUESTS & SEMINARS 41 42 EVENTS, VISITORS, GUESTS & SEMINAR EVENTS, VISITORS, GUESTS & SEMINARS 03 01 DECEMBER SEMINAR: DANDRITE Topical Seminar, PhD Student Kota Tokuoka, Kyoto University, Role of midbrain cholinergic inputs to the superficial layer of superior colliculus Anatomical and electrophysiological studies EVENTS, VISITORS, GUESTS & SEMINAR 06 10 11 12 13 14 09 10 11 11 11 13 SEMINAR: Distinguished iNANO Lecture, Professor Jay T. Groves, College of Chemistry, UC Berkeley, Biochemical signaling on membrane surfaces: the roles of space, force, and time, Host: Group Leader Poul Nissen EVENT: 44 18 15 SEMINAR: DANDRITE Topical Seminar, Postdoc Erica Ehrhardt, Janelia HHMI Research Campus & University of Cologne, The VNC project: generating a cell-type specific driver line library targeting ventral nerve cord of Drosophila melanogaster, Host: Grop Leader Anne von Philipsborn 19 AUGUS 45 17 18 20 20 19 21 EVENT: Group Leader and Team Leader Retreat Day, Program: Research in depth and Leadership. Venue: AROS Art Museum 22 SEMINAR: DANDRITE Topical Seminar, Dr. Jan Clemens, European Neuroscience Institute, Göttingen, From song to behavior in Drosophila, Host: Group Leader 46 28 29 SEMINAR: MBG Focus Talk, Professor Todd R. Graham, Vanderbilt University, Flippase-gate: Explorations Into How P4-ATPases Recognize Their Lipid Substrate, Host: Poul Nissen MAY EVENT: DANDRITE Mini Symposium, Aarhus University Lectures by: Professor Benjamin Eaton, University of Texas He 47 SAB MEETING & RETREAT 88 participants attended the 2018 Retreat and SAB meeting at Sandbjerg Manor in southernmost Denmark. DANDRITEs third Scientific Advisory Board (SAB) meeting were held on Monday May 13th to15th and was combined with the yearly retreat. The meeting took place at the confer 48 A vibrant part of the Retreat program was The Elevator Talk Session. All PhD and Postdoc made a two-minutes presentation of their research. From left top: PhD student Josephine Dannersø Nissen, PhD student Monica Dahlstrup Sietam, Postdoc Dongik Park, Postdoc Ana Oliveira, PhD student Mariam Gam 49 PROMEMO April 4th was the Official inauguration of PROMEMO: Center for Proteins in Memory - a Danish National Research Foundation Center of Excellence. PROMEMO is a brilliant example of a DANDRITE spin-off activity. The core researchers of PROMEMO are all related or directly part of DANDRITE. Th 50 Neuroscience Day 2018 Participants. Photo by Lars Kruse, AU Photo NEUROSCIENCE DAY EVENT: Neuroscience Day 2018: Rewarding Neuroscience. Organized by NeuroCampus Aarhus (NCA). NCA is a cross-disciplinary research network at Aarhus University and Aarhus University Hospital open for all intereste 51 Group Leader Duda Kvitsiani question from audience at Neuroscience Day 2018. Photo by Lars Kruse, AU Photo VIDEO PRODUCTIONS AND TWITTER Our dissemination and outreach efforts have in 2018 resulted in several video productions and with lively twitter activity via our account: twitter.com/dandri 52 PERSONNEL 04 Personnel PERSONNEL 53 54 PERSONNEL Personnel Each one of the five young group leaders during 2018 continued the successful establishment and build-up of their groups with students, technical support staff, and promising postdoctoral fellows. Additionally, all groups have attracted several summer students, interns, and PERSONNEL 35 Figure 3. Graphic representation of the personnel counts for 2018 (numbers grouped by appointment category and gender). The count is excluding affiliated researchers. 30 25 20 15 10 5 Female 0 Male Professor Senior Researcher Postdoc PhD Other staff Fig 4: Graphic representat 56 PERSONNEL Awards Award of the Carlsberg Foundation Research Prize 2018. From the Left Secretary-General of the Royal Danish Academy of Sciences and Letters Lars Arge, Minister of Higher Education and Science Tommy Ahlers, Prize winner Professor Tim Bollerslev, HRH Crown Princess Mary, Prize wi PERSONNEL 57 Grants 8 11 13 14 17 1. Group Leader Keisuke Yonehara: Infrastructure grant, DKK 0.15 million, Carlsbergfondet 10. Affiliated Researcher Olav Andersen: Splice variant in AD, DKK 75.000, Jascha Foundation 2. Affiliated Researcher Olav Andersen: DKK 38.000, New exon structure 58 19 21 21 19. PhD Student Alana Miranda Pinheiro: PhD fellowship: Satellite cells in neuropathic pain, DKK 1.6 million, , Lundbeckfonden 29. Affiliated Researcher Jørgen Kjems: NanoString infrastructure, DKK 0.8 million, Carlsberg Foundation 20. Affiliated Researcher Olav Andersen: Local 59 Patents Affiliated Researcher Jørgen Kjems (together with T.B. Hansen) obtained patent: Circular RNA for inhibition of microRNA, Patent WO/2014/082644. Group Leader Mark Denham obtained patent: Development of an artificial transgene for regulating Alpha-Synuclein in vivo. Passed patentability a 60 PERSONNEL Sadegh Nabavi: Activity-dependent retrograde labeling of brain circuits, SAN2018, Argentina Poul Nissen: Krystalsymmetri og et røntgenblik på livets molekyler, Folkeuniversitetet, Aarhus University, Denmark AUGUST Katherine Gill: Investigating Molecular pathways in Parkinsons disease PERSONNEL Poul Nissen: Enabling structure and mechanism based drug discovery on Ca2+ pumps and SLC6 transporters, Novartis, Basel, Switzerland Keisuke Yonehara: Visual motion processing in mice: cell types, circuits, and disease, Institute of Neuroinformatics, University of Zurich/ETH, Switzerland 62 PUBLICATIONS 05 Publications PUBLICATIONS 63 64 PUBLICATIONS Publications 1 1 Andersen JL, Gesser B, Funder ED, Nielsen CJF, Gotfred-Rasmussen H, Rasmussen MK, Toth R, Gothelf KV, Arthur JSC, Iversen L, Nissen P (2018) Dimethyl fumarate is an allosteric covalent inhibitor of the p90 ribosomal S6 kinases. Nat. Commun., Vol. 9, p. 4344 2 PUBLICATIONS 6 9 65 66 11 13 Duszkiewicz AJ, McNamara CG, Takeuchi T, Genzel L (2018) Novelty and Dopaminergic Modulation of Memory Persistence: A Tale of Two Systems. Trends in Neuroscience, Vol. 42, No. 2, p. 102-114 14 Dyla M, Kjærgaard M (2018) Naturens nanopumper fanget på film. Dansk Kemi, Vol. 8, No. 99, p. 10 67 25 28 Kros L, Lykke-Hartmann K, Khodakhah K (2018) Increased susceptibility to cortical spreading depression and epileptiform activity in a mouse model for FHM2. Sci Rep., Vol. 8, No. 1, p. 16959 29 Kundel F, De S, Flagmeier P, Horrocks MH, Kjaergaard M, Shammas SL, Jackson SE, Dobson CM, Klene 68 32 42 Peyrot WJ, ....Tracy AA. Christensen JH (member of: Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium (2018) Does Childhood Trauma Moderate Polygenic Risk for Depression? A Meta-analysis of 5765 Subjects From the Psychiatric Genomics Consortium. Biological Psy 69 38 54 Sølvsten C, de Paoli FV, Christensen JH, Nielsen AL (2018) Voluntary Physical Exercise Induces Expression and Epigenetic Remodeling of VegfA in the Rat Hippocampus. Molecular Neurobiology, Vol. 55, Issue 1 60 Tranebjærg L, Strenzke N, Lindholm S, Rendtorff ND, Poulsen H, Khandelia H, Kop 70 65 Watanabe T, Takeuchi T, Kubota N, Wainai T, Kataoka K, Nakaya T, Sugimoto A, Sato T, Ohira H, Tsujino I, Kumagai K, Kubota T, Hasegawa C, Tokuyama K, Ueki K, Yamauchi T, Mishina M, Kadowaki T (2018) A transgenic mutant mouse line accompanied by the complete deletion of interleukin-33 showed i FINANCIALLY SUPPORTED BY: DANDRITE IS THE DANISH NODE OF THE NORDIC EMBL PARTNERSHIP FOR MOLECULAR MEDICINE: DANDRITE is located at the following addresses at Aarhus University: Department of Molecular Biology and Genetics Gustav Wieds Vej 10 Building 3130 DK- 8000 Aarhus Department of Biomedicine Ole Worms Allé 8 Building 1182 DK- 8000 Aarhus Department of Biomedicine Høegh-Guldbergs Gade 10 Building 1116