Research Grant Award

Research Fellowship Award

Wright, Jane, PhD

Friedrich Miescher Institute, Basel, Switzerland
Elucidating the mechanism of ATX-2: the C.elegans ortholog of a protein implicated in human neurodegenerative disease.

Mutations in the human gene SCA2, which encodes the ataxin-2 protein, can give rise to the neurodegenerative disorders spinocerebellar ataxia type 2 and are also associated with Parkinson's disease. The typical biological function of the ataxin 2 protein is currently unknown. Our aim is to uncover this normal function of ataxin-2 in the hope that it will increase our understanding of what may go awry when ataxin-2 is mutated. In order for a gene to be expressed, the DNA of a gene is first transcribed into mRNA molecules. This mRNA can then serve as a template for the synthesis of proteins. Ataxin-2 has been suggested from previous studies (work of several labs including our own) to regulate the expression of mRNA molecules. It is possible that mutations in ataxin-2 may cause neurodegeneration by interfering with the normal regulation of particular mRNAs. We are studying the ataxin-2 protein in the round-worm, C. elegans (homolog, atx-2) to understand precisely how ataxin-2 usually regulates mRNA expression. The main advantage of studying atx-2 in C. elegans is that it is the only model where we already have examples of specific mRNAs whose expression is regulated by ATX-2. Also the ataxin-2 protein shows a high degree of evolutionary conservation making it entirely feasible to study in a model organism such as C.elegans. Future SCA2 therapies will likely be aimed at modulating the function of the ataxin-2 protein. Understanding the normal function of ataxin-2 will greatly aid this process.