Progetto:Investigating the mechanisms of long-range epigenetic gene regulation (LREGR) at the Friedreich’s ataxia (FRDA) locus.

Dr Mark Pook-Ataxia Research Group, Division of Biosciences, Brunel University, Uxbridge, UK

Since GAA repeat expansions in the frataxin gene were identified as the genetic cause of Friedreich’s ataxia in 1996, research in the field has rapidly progressed and at the same time our understanding of the complexity of the disease mechanisms has increased. In this context, we have recently shown that GAA repeat expansions, in addition to impairing the expression of the frataxin gene, can also impair the expression of a second gene named PIP5K1B and located near the frataxin gene. Based on these findings, we propose that GAA expansions may act at a distance to impair the expression of several surrounding genes, and this could have important consequences in Friedreich’s ataxia. Now, using cells in culture, we would like to pursue this work by:

1) determining which additional genes located near the frataxin gene are indeed affected,

2) understanding the molecular mechanisms responsible for these effects. This work may lead to the identification of additional target genes and novel mechanisms relevant to Friedreich’s ataxia,which might result in the design of new therapeutic strategies to counteract the disease.

GoFAR has come to award an additional research grant of 5.000 £ to Dr.M. Pook.