José Manuel Horcas Nieto

TABLE OF CONTENTS Chapter 1: General Introduction 7 Chapter 2: Organoids as a model to study intestinal and liver dysfunction in severe malnutrition 33 Chapter 3: Towards Automatization of Organoid Analysis: A Deep Learning Approach to Localize and Quantify Organoids Images 73 Chapter 4: Docosahexaenoic acid prevents peroxisomal and mitochondrial protein loss in a murine hepatic organoid model of severe malnutrition 89 Chapter 5: Establishing a peroxisomal β-oxidation computational kinetic model to understand the effects of amino-acid restriction on peroxisomal β-oxidation 129 Chapter 6: iPSC-derived liver organoids as a tool to study Medium Chain Acyl-CoA Dehydrogenase deficiency 167 Chapter 7: General Discussion 201 Appendices Summary 218 Samenvatting 222 Resumen para público no científico 227 Acknowledgments 232 Curriculum vitae 238 List of publications 240

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