Over the past year Friends has been communicating with Neil Camarta of FSHD Canada Foundation regarding co-funding projects that both our groups agree are of top importance. This process not only doubles the value of your contributes by splitting the cost 50-50, but also allows for additional critical review of research proposals to ensure your donations are only used on the most promising research. We have so far agreed on three, which you may have seen previously posted:
Identification of small RNAs generated from the D4Z4 Array [Galina Filippova & Daniel G Miller]
These same researchers have previously shown that multiple transcripts and small RNAs are expressed from D4Z4. They now hypothesize that small RNAs generated from D4Z4 long non-coding transcripts are involved in heterochromatin formation and therefore DNA methylation that result in DUX4 epigenetic silencing. They propose to identify these RNAs by deep sequencing of small RNA populations in cells from FSHD-affected and unaffected people.
Identification of Chromatin Modifier Genes Important for DUX4 Silencing [Daniel G Miller & Galina Filippova]
This proposal builds on the hypothesis that epigenetic modification of D4Z4 chromatin structure is an important strategy for disease treatment. They propose to construct a library of siRNA’s (artificial RNA’s) that target genes involved in chromatin modification and examine the effect of reducing transcript levels on DUX4 gene expression to determine integral components of the DUX4 transcriptional silencing machinery.
Generating FSHD-affected human muscle in mice for testing therapeutic strategies [Maura H Parker]
Maura proposes to generate human FSHD-affected muscle within mice. She will do this by transplanting muscle stem cells from FSHD-affected individuals into the regenerating muscle of mice. Based on her current studies, she expects to generate a muscle within the mouse that is 90% human-derived. These mice will be important for studying the disease in the context of an individual, yet sparing patients the pain of multiple muscle biopsies. Most importantly, these mice will be essential for pre-clinical testing of potential therapies.