Pasteurella multocida toxin as a tool to modulate bone and immune cell differentiation

• Applicant: Professorin Dr. Katharina Hieke-Kubatzky
• Subject Area: Immunology ; Rheumatology
• Term: from 2010 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 169332709

The project will investigate the connection between B-cell and osteoclast differentiation, using the bacterial toxin from Pasteurella multocida (PMT) as a model system. PMT is a potent mitogen with known osteoclastic properties that stimulates differentiation of bone marrow cells into osteoclasts and inhibits osteoblast function, respectively. The aim of the project is to further elucidate the mechanism of PMTinduced osteoclast differentiation and to define the role of B-cells in that process. We aim to characterise the PMT-generated B-cell and osteoclast populations and their interaction or dependence of each other. We will investigate the mechanism of that interaction on a molecular level by characterising the secreted factors and by comparing the secretome and proteome of PMT and IL7, M-CSF/RANKL or LPS derived osteoclasts. In addition, we aim to define the signalling networks involved in the interplay between B-cells and osteoclasts, with a focus on anti-apoptotic signalling through Akt and Pim kinases and the importance of migration and adhesion to further expand our understanding of the regulation of bone destruction by immunological processes.

• DFG Programme: Priority Programmes
• Subproject of: SPP 1468: Osteoimmunology - IMMUNOBONE - A Programme to Unravel the Mutual Interactions between the Immune System and Bone
• Participating Persons: Professor Dr. Thomas Dörner; Dr. Annette Garbe; Professor Dr. Rudolf Manz