Our research activities are divided into four work packages and are all headed by a work package leader.
Work package 1: Target Discovery
Leader: Dr. Stephan Schulte-Merker; Hubrecht Institute, Utrecht.
Members: Hubrecht Institute
This work package will use innovative approaches to uncover genes essential for the function of osteoblasts (bone cells)and thus for bone formation.
There are three goals:
To identify highly validated targets in the area of bone formation, using a zebrafish model;
To explore the role of microRNAs and their effector genes in osteoblast function;
To generate 250 different GPCR (G-protein coupled receptors) mutant zebrafish — providing a library of pharmaceutically relevant test cases for all consortium members to test their specific assays.
This powerful resource will be unique in the world, and would be impossible without the national-level funding provided by the Smart Mix program.
Work package 2: Screen Technology
Leader: Prof. dr. Christina Vandenbroucke-Grauls; Vrije Universiteit Medisch Centrum, Amsterdam.
Deputy: Dr. Wilbert Bitter; Vrije Universiteit Medisch Centrum, Amsterdam.
Members: Vrije Universiteit Medisch Centrum Amsterdam, ZF-Screens BV, Fytagoras BV, Leiden University IBL (Institute of Biology Leiden), Leiden University LIACS (Leiden Institute of Advanced Computer Science).
This work package has the task of developing tools for the automation of zebrafish screens, particularly at the sorting, induction and readout stages. Using its expertise in software design and image analysis, this work package will transform our screens into efficient, high-throughput assays. Initially, our screening technologies will be perfected on zebrafish models within the expertise field of the work package members, namely infection and inflammation. The inflammation assays will add to the objectives of work package 4 on inflammatory bone and joint disease. The screen technologies, and the screens themselves, will be patented and licensed. Furthermore, they will be available to other work packages of this consortium (notably WP 1 and 3).
Work package 3: Drug Discovery
Leader: Prof. E. Ronald de Kloet; Leiden-Amsterdam Center for Drug Research (LACDR), Leids Universitair Medisch Centrum (LUMC).
Deputy: Dr. Marcel Schaaf, Leiden University IBL (Institute of Biology).
Members: Leiden-Amsterdam Center for Drug Research (LACDR), Progentix BV, Leiden University IBL (Institute of Biology), Leiden University LIC (Institute of Chemistry), GlaxoSmithKline (United Kingdom), Serpo, Radboud University Nijmegen.
This work package is tasked with developing and validating phenotype-based assays, and the screening of pre-selected compound libraries from an industrial partner. One of the principal aims is to show that established mammalian assays can indeed be transferred successfully to the zebrafish. An additional partner company is involved in developing novel bone implants for orthopedic surgery and will use this work package’s bone-formation assays to develop new products. The bone assay of WP 1 and the inflammation assay of WP 2 will be taken, further validated, and used for the screening of pre-selected compound libraries. Further, this work package will spin-off towards other disease areas by developing behavioural assays.
Work package 4: Clinical Development
Leader: Dr. Richard Janssen; BioFocus DPI BV
Members: BioFocus DPI BV, Academic Medical Center (AMC) Amsterdam, Agendia BV, Arthrogen BV.
This work package seeks to develop disease-modifying drugs against two major bone and joint diseases: rheumatoid arthritis (RA) and osteoarthritis (OA). Several partners will be involved in this work package each with their own task. Galapagos BV and its sister organization BioFocus DPI will develop oral drugs for the treatment of OA and Arthrogen will develop gene therapy for the treatment of various forms of arthritis, including RA and inflammatory OA. Agendia provides tools for validation of targets and compounds and develops prognostic and predictive tests for RA. AMC will provide patient specimens for target and drug validation and perform a phase I/II clinical trial in RA.
