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Novartis Institutes for BioMedical Research

5 ARTICLES PUBLISHED IN JoVE

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Medicine

Utilizing Murine Inducible Telomerase Alleles in the Studies of Tissue Degeneration/Regeneration and Cancer
Takashi Shingu 1, Mariela Jaskelioff 2, Liang Yuan 1, Zhihu Ding 3, Alexei Protopopov 4, Maria Kost-Alimova 4, Jian Hu 1
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.

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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 Eggan 2,3, Ajamete Kaykas 1
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.

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Cancer Research

Generation of High-Throughput Three-Dimensional Tumor Spheroids for Drug Screening
Lesley Mathews Griner 1, Kalyani Gampa 1, Toan Do 2, Huyen Nguyen 2, David Farley 2, Christopher J. Hogan 2, Douglas S. Auld 2, Serena J. Silver 1
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.

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Neuroscience

A High-throughput Calcium-flux Assay to Study NMDA-receptors with Sensitivity to Glycine/D-serine and Glutamate
Fred Yeboah 1, Hongqiu Guo 1, Anke Bill 1
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.

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Biology

Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity
Adeline Unterreiner *1, Ratiba Touil *1, Daniele Anastasi 1, Nicolas Dubois 1, Satoru Niwa 1, Thomas Calzascia 1, Frederic Bornancin 1
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.

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