iPSC stained with DAPI (blue, nucleus) and MMUT (green, mitochondria)
courtesy of Baumgartner lab (Matthew Denley)
Director Research & Education, University Children's Hospital Zurich
Head, Division of Metabolism, University Children's Hospital Zurich
Research Focus: Our research focuses on inherited disorders of methylmalonic aciduria, a rare but life-threatening vitamin B12-related disease which usually presents in the newborn or childhood period. We are using many different approaches to understand disease pathomechanisms and develop novel therapeutic options. Fundamentally, we explore structural biology, cellular biology and biochemistry in our cellular and animal models of disease. In one approach, the group has established multiple patient and control iPSC lines. We are using these to investigate the importance of proteins involved in methylmalonic aciduria, including MMUT, to cell growth and mitochondrial health and have established a cortical differentiation protocol to model neural development, as neurological dysfunction is an important aspect of disease. We will further expand our repertoire to include CRISPR-Cas9 derived isogenic controls as well as 2D striatal differentiation and 3D organoids, which will be ideal for high-content screening of therapeutic molecules.
Methods: fibroblast reprogramming, Sendai virus, clonal selection, 2D cortical neuronal differentiation, CRISPR/Cas9 genome editing
Keywords: vitamin B12, methylmalonic aciduria, biochemistry, iPSC, neurons, drug development
Topics: metabolism, rare disease
|Prof. Dr. Ferdinand von Meyenn
Professor of Nutrition and Metabolic Epigenetics
Institute of Food, Nutrition and Health
Research Focus: Changes in cellular metabolism reflect the balance between intrinsic requirements of a cellular state and adaption to varying extrinsic environments. Metabolic pathways are emerging as a key regulatory mechanism to control cellular function, potential, and state through the dynamic regulation of the epigenome. In particular embryonic development is characterised by significant metabolic, epigenetic and cellular changes associated with different developmental stages, suggesting that metabolism may play a key role in regulating cell fate decisions. But until now, the precise molecular interplay between metabolism and the epigenome remains poorly understood.
Our main goal is to understand the mechanisms that link metabolism with epigenetic changes and cellular potential, focusing on pluripotent stem cells and early embryonic development. We are building a comprehensive dataset of metabolic states in human and mouse stem cells and are assessing the impact of induced metabolic changes on PSC potential, histone and DNA methylation, and the relevant epigenetic enzymes. Elucidating these mechanisms will reveal molecular principles involved in the regulation of the epigenome and affecting PSC potential and state. This knowledge will form the basis for novel PSC differentiation strategies for regenerative medicine and will also contribute to our understanding of metabolic disease states and ageing.
Methods: Human and mouse embryonic stem cells; lineage reprogramming; resetting to naive pluripotency; metabolic regulation; epigenetic resetting; next-generation sequencing
Keywords: embryonic stem cells, naive pluripotency, metabolism, epigenetics
Topics: pluripotency, metabolism, epigenetics