Molecular dissection of hippocampal inhibitory interneuron circuits
Glioblastoma multiforme (GBM), which represents the most prevalent type of malignant brain tumor in adults, is highly resistant to current medical interventions. The high resistance is associated with the relentless infiltration of the brain by the tumor cells.
The purpose of this project is to identify the cellular mechanism underlying the infiltration of glioblastoma in the brain. Specifically, we will transplant patient-derived tumor cells into the mouse brain. We will (1) manipulate genes that control the nuclear integrity of tumor cells and determine the effect of these manipulations on the spread of tumor cells in the host brain; (2) analyze neuron and cancer cell interaction in the host brain.
To avoid the rejection of transplanted tumor cells, we will use 90 immunodeficient mice (45 SCID mice, stock No: 001913 from the Jackson laboratory and 45 NOD SCID mice, Strain Code: 634, Charles River). To maintain the integrity of the 3Rs of animal research, we have conducted preliminary experiments by transplanting tumor cells into neuronal cultures (Replacement). These in vitro results have already identified several potential molecular mechanisms underlying the tumor infiltration, thereby allowing us to reduce the number the in vivo experiments with appropriate experiment design. Finally, we will take advantage of state-of-the-art approaches to minimizing the pain and suffering associated with the experiments (Refinement).
We are aware that the proposed experiments are associated with moderate harmful effects in terms of animal welfare. However, this factor is well compensated for by the high gain. Specifically, the proposed project has a strong potential to open new therapeutic avenues for combating the most malignant brain tumor in human patients. Through a close interaction with local veterinarians, we aim for finding a good balance between improving public health and the welfare of animals in research.
The purpose of this project is to identify the cellular mechanism underlying the infiltration of glioblastoma in the brain. Specifically, we will transplant patient-derived tumor cells into the mouse brain. We will (1) manipulate genes that control the nuclear integrity of tumor cells and determine the effect of these manipulations on the spread of tumor cells in the host brain; (2) analyze neuron and cancer cell interaction in the host brain.
To avoid the rejection of transplanted tumor cells, we will use 90 immunodeficient mice (45 SCID mice, stock No: 001913 from the Jackson laboratory and 45 NOD SCID mice, Strain Code: 634, Charles River). To maintain the integrity of the 3Rs of animal research, we have conducted preliminary experiments by transplanting tumor cells into neuronal cultures (Replacement). These in vitro results have already identified several potential molecular mechanisms underlying the tumor infiltration, thereby allowing us to reduce the number the in vivo experiments with appropriate experiment design. Finally, we will take advantage of state-of-the-art approaches to minimizing the pain and suffering associated with the experiments (Refinement).
We are aware that the proposed experiments are associated with moderate harmful effects in terms of animal welfare. However, this factor is well compensated for by the high gain. Specifically, the proposed project has a strong potential to open new therapeutic avenues for combating the most malignant brain tumor in human patients. Through a close interaction with local veterinarians, we aim for finding a good balance between improving public health and the welfare of animals in research.