|Somatic stem cells require a tight balance between proliferation and quiescence to ensure life-long replenishment of tissues. A disturbance in this balance can have severe consequences. The role of metabolism in this process has only recently gained attention and remains poorly understood. A better knowledge of metabolic stem cell regulation may offer new avenues to control stem cell behavior and may have important clinical implications.|
The main focus of the Laboratory of Stem Cell Metabolism are adult neural stem cells (NSPCs), which give rise to new neurons throughout adulthood. This process is called adult neurogenesis and has been shown to be disturbed in various cognitive diseases. We are interested in the metabolic regulation of neurogenesis in health, aging and disease, covering basic aspects of metabolic regulation as well as extrinsic influences on NSPC metabolism.
Furthermore, we are exploring whether there are common mechanism of metabolic regulation in different somatic stem cell compartments.
We are using innovative techniques such as CRISPR/Cas9 mediated genetic modifications, various transgenic mouse models, virus-mediated gene expression in vitro and in vivo, time-lapse imaging, mass spectrometry imaging as well as proteomic, metabolomic and lipidomic approaches to address the following main topics:
1. Basic biology of lipid metabolism in NSPCs.
We have previously shown that lipid metabolism is indeed crucial for NSPC behavior (Knobloch et al. Nature 2013, Knobloch et al. 2017, in revision). However, why these lipids are so important for NSPCs and how they exert their influence on NSPC behavior remains poorly understood. We will address how lipid metabolism changes during cell cycle, fate choice and differentiation, and what the lipids are used for.
2. Extrinsic influences on metabolism in NSPCs.
Many extrinsic factors are known to influence neurogenesis, such as for instance nutrition, physical activity, aging and various diseases. However, how this pro-and anti-neurogenic stimuli are translated into changed NSPC behavior remains unclear. We will address how NSPC metabolism changes upon these different stimuli.
3. Common mechanisms of metabolic regulation in different somatic stem cell compartments.
It is highly likely that different somatic stem cells share similar mechanisms of metabolic regulation. However, this possibility has not been addressed in depth. We will compare metabolic processes in different somatic stem cells, focusing on lipid metabolism, to determine the degree of conserved stem cell control mechanisms.
Marlen Knobloch, Assistant Professor
Marlen Knobloch has obtained her PhD at the University of Zurich in the Group of Prof. Nitsch, where she developed and characterized a novel mouse model for Alzheimer’s disease. During her PhD, she furthermore contributed to an innovative immunization approach against Alzheimer’s disease, which is currently in a clinical phase 3 trial led by Biogen.
Dr. Knobloch moved on to do her postdoc in the Group of Prof. Jessberger at the University of Zurich, where she has been studying the metabolic requirements of adult neural stem cells. Her work has uncovered important novel mechanisms how lipid metabolism controls neural stem cell activity. She has further been a guest postdoc at EPFL in the Group of Prof. Luetolf.
In 2017, Dr. Knobloch has obtained an assistant professorship in the Department of Physiology at the University of Lausanne where she has established the Laboratory of Stem Cell Metabolism.
Sofia Madsen, PhD student
|Sofia obtained her Bachelor and Master in Biomedicine at Lund University. She did her master thesis in Johan Jakobsson’s lab, where she studied the role of autophagy and miRNA biogenesis in various mutant huntingtin overexpressing models. Thereafter she stayed in Johan Jakobsson’s lab for additional internships where she worked with CRISPR/Cas9 to study epigenetics in neurons. Sofia joined Marlen Knobloch’s group in June 2017 as a PhD student and is currently working on the role of lipid droplets in neural stem cells.|
Justine Vanille Maillard, Lab technician
Vanille joined the Departement of Physiology in 2017. During the two years of her apprenticeship, she were trained by the group of Marie-Gabrielle Zurich, Christian Widmann and the Platform of Metabolomics. Currenty, she is the lab technician working for both Marlen Knobloch’s lab and Marie-Gabrielle Zurich’s lab. She is involving in cell cultures of iPSCs, NPCs, human 3D brain culture, human brain organoid culture, in enzymatic activity analyses, real-time RT-PCR, immunostaining, immunoblotting and in metabolic profiling using Seahorse technology. She manages the lab and is involved in numerous projects with all group members.
Francesco Petrelli, Research Associate
Francesco obtained his Master- and PhD degree in Italy at University of Calabria, studying the roles of glial cells in neuroinflammation and neurodegeneration. Afterwards, he moved as a Post-Doc in Paola Bezzi’s Lab at the University of Lausanne, where he studied the role of astrocytes in the modulation of dopamine levels during postnatal cortex development. Thereafter, he joined the lab of Jean-Claude Martinou at the University of Geneva, as a Research Associate, where he is investigating, in collaboration with Marlen Knobloch’s lab, the effect of Mitochondria Pyruvate Carrier 1 deletion on astrocytes and neural stem cells. Francesco has joined Marlen Knobloch’s lab as a Research Associate in April 2020 and is currently working on lipid metabolism of glial cells in physiological and pathological conditions
Mergim Ramosaj, PhD student
Mergim obtained his Bachelor in Biology and his Master in Molecular Life Science at the University of Lausanne. During his pre-master thesis, he worked on the identification of factors necessary for the survival of primary CD4+ T cells in culture under the supervision of Angela Ciuffi. Then, he joined Nicole Déglon’s lab for his master thesis. During his master, he worked on small interfering RNAs for Huntington’s disease and more precisely on evaluation of lentiviral vector retrograde transport and optimization of cutting edge tools for pre-clinical validation of this approach. Mergim joined Marlen Knobloch’s group in April 2017 as a PhD student and is currently working on the role of lipid droplets in neural stem cells.
Valentina Scandella, PhD student
Valentina obtained her Bachelor in Biology and her Master in Medical biology at the University of Lausanne. As a first step project, she joined Caroline Pot’s group where she worked on the interplay between lipid metabolites and gut flora during experimental autoimmune encephalomyelitis. For her master thesis, she joined Olivier Bonny’s lab. She was interested in the effect of vitamin D on the level of serum and urinary uric acid and on the expression of the different urate transporters. Thereafter, she worked as a scientific collaborator in Dmitri Firsov’s group for 6 months. She started a project to investigate the role of the peroxisomes in the kidney and she joined Marlen Knobloch’s lab in September 2018 as a PhD student. Valentina is working on the metabolic profile of adult neural stem cells.
Daniel Sudria Lopez, PhD student
Daniel obtained his Bachelor in Biomedicine at the University of Barcelona and his master in Neuroscience at the University of Regensburg. During his master’s thesis in Christian Wetzel’s lab, he studied the mitochondrial function of fibroblasts obtained from depressed patients and optimized protocols to convert them into iPSCs and neurons. In addition, Daniel obtained a second master’s degree in Bioinformatics and Biostatistics at the Open University of Catalonia. During this master’s thesis under the supervision of Melchor Sanchez Martinez, Daniel worked on the computational design of molecules with a therapeutic potential for the treatment of Niemann-Pick type C disease. Daniel joined Marlen Knobloch’s lab in July 2018 as a PhD student and is currently working on establishing cerebral organoid systems for the study of lipid metabolism during development.
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