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Mechano-regulation of cellular interplay between mesenchymal, hematopoietic and vascular systems in the bone marrow microenvironment
Bone marrow tissues are essential for sustained production of blood cellular components, the continuous remodeling of bone and efficient immune responses. This project aims to investigate the mechano-regulation of mesenchymal, hematopoietic and vascular systems in the bone marrow microenvironment.
Keywords: 3D confocal microscopy, in vivo micro-CT, bone marrow microenvironment, stem cells, niche, mechano-regulation
Bone marrow tissues are essential for the sustained production of blood cellular components, the continuous remodeling of bone surfaces and the mounting of efficient immune responses. The sophisticated regulation of these biological processes is achieved through the complex cellular interplay established between bone marrow mesenchymal (bone-forming), hematopoietic and vascular systems present. A key unresolved question is how mechanical forces acting on bone shape the tissue microarchitectural organization, the cellular composition and the function of underlying bone marrow tissues. To address these questions, global approaches are needed that enable the registration of mechanical effects in bone morphology, the visualization of subsequent vascular remodeling and changes in extracellular matrix structure and the analyses of cellular content in single bones. The aim of this project is to combine powerful multidimensional imaging and cytometry technologies developed in the laboratory of Prof. Ralph Müller (ETH) and Prof. César Nombela-Arrieta (UZH, USZ) to provide such comprehensive data. The student will work in integrating imaging data from bone surfaces obtained using dynamic in vivo micro-CT, with 3D fluorescence confocal microscopy of bone and marrow tissues at subcellular resolution, and advanced flow cytometric techniques. Ultimately, the student will perform an exploratory analysis on how mechanical loading modifies the microenvironment and hematopoietic stem cell regulation in murine bone marrow. Students with strong interest in state of the art imaging technologies and computational analyses are encouraged to apply.
Bone marrow tissues are essential for the sustained production of blood cellular components, the continuous remodeling of bone surfaces and the mounting of efficient immune responses. The sophisticated regulation of these biological processes is achieved through the complex cellular interplay established between bone marrow mesenchymal (bone-forming), hematopoietic and vascular systems present. A key unresolved question is how mechanical forces acting on bone shape the tissue microarchitectural organization, the cellular composition and the function of underlying bone marrow tissues. To address these questions, global approaches are needed that enable the registration of mechanical effects in bone morphology, the visualization of subsequent vascular remodeling and changes in extracellular matrix structure and the analyses of cellular content in single bones. The aim of this project is to combine powerful multidimensional imaging and cytometry technologies developed in the laboratory of Prof. Ralph Müller (ETH) and Prof. César Nombela-Arrieta (UZH, USZ) to provide such comprehensive data. The student will work in integrating imaging data from bone surfaces obtained using dynamic in vivo micro-CT, with 3D fluorescence confocal microscopy of bone and marrow tissues at subcellular resolution, and advanced flow cytometric techniques. Ultimately, the student will perform an exploratory analysis on how mechanical loading modifies the microenvironment and hematopoietic stem cell regulation in murine bone marrow. Students with strong interest in state of the art imaging technologies and computational analyses are encouraged to apply.
The goal is to establish computational methods to correlate data obtained by multiple imaging approaches using registration techniques previously developed in the Müller lab. By means of these techniques we aim to quantify the effects of mechanical loading in the mesenchymal, hematopoietic and vascular components of the marrow.
The goal is to establish computational methods to correlate data obtained by multiple imaging approaches using registration techniques previously developed in the Müller lab. By means of these techniques we aim to quantify the effects of mechanical loading in the mesenchymal, hematopoietic and vascular components of the marrow.
Prof. Dr. Ralph Müller, ram@ethz.ch, Institute for Biomechanics, ETH Zürich, Professorship Ralph Müller;
Prof. Dr. César Nombela Arrieta, Cesar.NombelaArrieta@usz.ch, Department of Experimental Hematology, University Hospital Zurich and University of Zurich
Prof. Dr. Ralph Müller, ram@ethz.ch, Institute for Biomechanics, ETH Zürich, Professorship Ralph Müller; Prof. Dr. César Nombela Arrieta, Cesar.NombelaArrieta@usz.ch, Department of Experimental Hematology, University Hospital Zurich and University of Zurich