Fenghua Hu, research scientist at Cornell University in Ithaca, N.Y., was awarded an MDA research grant totaling $360,000 over a period of three years to study the effects of TDP43 gene mutations in a model of amyotrophic lateral sclerosis (ALS).
Mutations in the TDP43 gene have been shown to cause ALS in some instances. Even in individuals with ALS who do not have TDP43 mutations, the TDP43 protein usually clumps together abnormally, forming aggregates within muscle-controlling nerve cells called motor neurons. “This suggests that the misbehavior of TDP43 protein could cause neurodegeneration,” Hu says.
The TDP43 protein found in the aggregates is often just a piece of the whole protein, indicating it has been cleaved. It is also often “tagged” with a smaller protein, called ubiquitin, used by the cell to mark a protein for destruction and recycling. “However, the role of TDP43 fragments and ubiquitination in disease progression is still not clear,” Hu says.
She plans to develop a model of ALS using zebrafish, a small and fast-growing fish used as a lab model for the study of many diseases. In the fish, she will study how TDP43 protein fragments induce toxicity and cause neurodegeneration, which should help researchers develop better targets for therapy in ALS.
Funding for this MDA grant began Feb. 1, 2013.