Novartis Institutes for BioMedical Research 5 articles published in JoVE Biology Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity Adeline Unterreiner*1, Ratiba Touil*1, Daniele Anastasi1, Nicolas Dubois1, Satoru Niwa1, Thomas Calzascia1, Frederic Bornancin1 1Autoimmunity, Transplantation and Inflammation, Novartis Institutes for BioMedical Research MALT1 regulates innate immunity but how this occurs remains ill-defined. We used the selective MALT1 paracaspase inhibitor MLT-827 to unravel the contribution of MALT1 to innate signaling downstream of Toll-like or C-type lectin-like receptors, demonstrating that MALT1 regulates the production of myeloid cytokines, and downstream of C-type lectin-like receptors, selectively. Cancer Research Generation of High-Throughput Three-Dimensional Tumor Spheroids for Drug Screening Lesley Mathews Griner1, Kalyani Gampa1, Toan Do2, Huyen Nguyen2, David Farley2, Christopher J. Hogan2, Douglas S. Auld2, Serena J. Silver1 1Oncology Drug Discovery: Molecular Pharmacology, Novartis Institutes for Biomedical Research, 2Chemical Biology and Therapeutics, Novartis Institutes for Biomedical Research Across a wide variety of disease indications, more physiologically relevant models are being developed and implemented into drug discovery programs. The new model system described here demonstrates how three-dimensional tumor spheroids can be cultured and screened in a high-throughput 1536-well plate-based system to search for new oncology drugs. Neuroscience A High-throughput Calcium-flux Assay to Study NMDA-receptors with Sensitivity to Glycine/D-serine and Glutamate Fred Yeboah1, Hongqiu Guo1, Anke Bill1 1Chemical Biology and Therapeutics, Novartis Institutes for BioMedical Research The goal of this protocol is to facilitate the study of NMDA-receptors (NMDAR) at a larger scale and allow the examination of modulatory effects of small molecules and their therapeutic applications. Neuroscience Modelling Zika Virus Infection of the Developing Human Brain In Vitro Using Stem Cell Derived Cerebral Organoids Max R Salick*1, Michael F Wells*2,3, Kevin Eggan2,3, Ajamete Kaykas1 1Department of Neuroscience, Novartis Institutes for BioMedical Research, 2Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, 3Department of Stem Cell and Regenerative Biology and Harvard Stem Cell Institute, Harvard University This protocol describes a technique used to model Zika virus infection of the developing human brain. Using wildtype or engineered stem cell lines, researchers may use this technique to uncover the various mechanisms or treatments that may affect early brain infection and resulting microcephaly in Zika virus-infected embryos. Medicine Utilizing Murine Inducible Telomerase Alleles in the Studies of Tissue Degeneration/Regeneration and Cancer Takashi Shingu1, Mariela Jaskelioff2, Liang Yuan1, Zhihu Ding3, Alexei Protopopov4, Maria Kost-Alimova4, Jian Hu1 1Department of Cancer Biology, UT MD Anderson Cancer Center, 2Novartis Institutes for Biomedical Research, 3Sanofi US, 4Institute of Applied Cancer Science, UT MD Anderson Cancer Center Telomere and telomerase play essential roles in ageing and tumorigenesis. The goal of this protocol is to show how to generate two murine inducible telomerase knock-in alleles and how to utilize them in the studies of tissue degeneration/regeneration and cancer.
