Woodhouse-Sakati syndrome – From a new premature aging disorder towards aging mechanisms

• Applicant: Dr. Daniela Bakula
• Subject Area: Cell Biology
• Term: from 2017 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 393041795

The global increase in the elderly population is one of the greatest and most profound challenges confronting societies worldwide. Since the prevalence of most chronic diseases increases drastically with age it is critical to deepen our understanding of the mechanistic basis of aging. Through in silico analysis, I now report the discovery of a new premature aging disorder called Woodhouse-Sakati syndrome that may represent a unique model for human aging. Woodhouse-Sakati syndrome is a rare autosomal recessive disorder caused by mutation of the DCAF17 gene and characterized by diabetes, hearing loss, hair loss and neurodegeneration. Notably, the function of DCAF17 is so far completely uncharacterized and it is currently unclear how the loss of DCAF17 function contributes to the premature aging phenotype. My preliminary data indicates a function for DCAF17 in DNA repair mechanisms. Thus, I propose that the premature aging phenotype in Woodhouse-Sakati patients is provoked by genomic instability and energetic dysfunction due to the loss of DCAF17. Loss of DCAF17 function will be investigated in DCAF17 knockout mouse model, as well as in human embryonic stem cells differentiated into neuronal lineages. Classical DNA repair assays will be used to elucidate the function of DCAF17 in the DNA damage response. Further, transcriptome, metabolome and proteome analysis will be included to broaden the insight into DCAF17 function causing the premature phenotypes. In sum, I will utilize cutting edge in silico, in vitro and in vivo methodologies to shed light on the central question: What drives aging?

• DFG Programme: Research Fellowships
• International Connection: Denmark
• Host: Dr. Morten Scheibye-Knudsen