Grant: Operating Grant

Our proposal addresses fundamental aspects of molecular, cellular and developmental biology relevant to our understanding of human disease. We are determining how molecular complexes control the architecture of the outer membrane that surrounds each individual cell found in the body. This outer membrane is critical for the cell shapes and cell-cell interactions underlying the development and maintenance of tissues and organs. The outer membrane is controlled by cellular signals that organize molecular cables to pull on the membrane from within. By pulling the membrane inward, cells can divide to grow tissues, and they can pull on neighbouring cells to re-shape tissues. We recently discovered a novel molecular mechanism for keeping these molecular cables in check. We hypothesize that this restraint mechanism physically removes the cellular signals for cable formation from the outer membrane. In this way, abnormally strong pulling forces can be avoided so that cells divide and interact properly. To test this hypothesis we are using the experimental work-horse Drosophila melanogaster (the fruit fly). The molecules that organize cells and tissues in Drosophila are equivalent to those that organize cells and tissues in humans, and Drosophila has major advantages experimentally. Thus, Drosophila is an important model for discovering and studying molecules that contribute to human disease. The molecules we study are conserved from flies to humans and have been implicated in cancer progression. The cellular processes we study are also relevant to cancer. Abnormal cell division leads to gene loss or gene gain with changes to gene expression that can promote cancer growth. Abnormal cell-cell interactions can allow cancer cells to detach from their neighbours promoting cancer spread and metastasis. Our fundamental research will provide novel strategies for the control of cancer.