The recent identification of the gene asssociated with Friedreich's ataxia (FA) has provided an exciting opportunity to learn more about the molecular pathenogenesis of this devastating, progressively debilitating disease. The gene, termed X25, was found to contain an expanded GAA trinucleotide repeat within the first intron in the vast majority of FA patients, which presumably leads ultimately to an absent or severely reduced level of its coded protein """"""""frataxin"""""""". However, no direct studies have yet been reported on frataxin. Unffl this occurs, the cellular pathophysiology leading to the disease wffl remain a mystery, and the development of specific treatment strategies will be hindered. The experiments outined in this proposal are therefore directed toward understanding the normal cellular function of frataxin.
In Specific Aim 1, we propose to develop and characterize affinity- purified polyclonal antisera which specifically recognize frataxin. Preliminary studies have already demonstrated that antibodies raised to recombinant frataxin recognize proteins in human tissue homogenates that may correspond to ftataxin.
In Specific Aim 2, we will utilize the antibodies developed in Specific Aim 1 to determine the tissue, cellular, and subcellular distribution of frataxin in mice and human control tissues. Since protein function is largely determined by protein-prqtein interactions, we will attempt to identify frataxin- associated proteins in Specific Aim 3. In addition to these research activities, this proposal is being submitted as part of an overall career development plan. As such, additional clinical and didactic activities are outlined which will provide the principal investigator an excellent opportunity to continue his development as an academic neurologist and help to ensure his success as a research scientist.
