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A Genetic Model for Neurofibromatosis Type II

Sarah Hughes

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Canadian Institutes of Health Research (CIHR)
Neurofibromatosis Type II (NF2) is a crippling cancer, mostly of the nervous system. The chance of developing NF2 depends on the genes you inherit. For example, NF2 patients are often born only one functional copy the NF2 gene instead of two. If that functional copy was mutated, tumours may repeatedly develop in the brain and spinal cord. The NF2 gene encodes a protein named Merlin. Merlin acts as a tumour suppressor, a name for proteins that instruct cells not to divide. This activity may be related to a second function for Merlin: it helps cells to "stick together," which is crucial for forming various organs within our bodies. Our laboratory is determining why Merlin is found in almost all cells of the human body, but mutations in the NF2 gene mostly induce cancer in just the brain and spinal cord. Other researchers that study the Merlin protein mostly work with isolated human cells for simplicity, but that approach makes it more difficult to determine how Merlin causes cells to adhere to one another to form tissues like the brain. Animal models such as mice would be vastly preferable for tissue studies, but they are more difficult to work with than isolated cells. At the crossroads between cells and mice is the commonly studied laboratory animal Drosophila or the fruit fly. The fly brain is a reduced version of the human brain, with the same types of cells acting in the same ways. Using flies, we have shown that Merlin needs to work with other proteins to perform its tumour suppressor and cell-adhesive functions. Notably, some of these other proteins are found only in brain cells. We plan to determine how these proteins assist Merlin activity in the fly brain. We already know that related forms of these proteins are found in the human brain. Our goal is to understand how these proteins function with Merlin to control how cells grow and stick together in the nervous system. Our results will aid the development of improved diagnosis and therapies for NF2 tumours.

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