Navigation auf uzh.ch

Suche

URPP ITINERARE

Research project on Remethylation Disorders

Epigenetic changes in remethylation disorders: a novel target

Inherited disorders of remethylation represent inborn errors of folate and vitamin B12 metabolism. Clinically, patients show life threatening disease and have impaired neurological development. Since remethylation is required for the production of S-adenosylmethionine (SAM), the primary substrate for epigenetic methylation of DNA and histones, there is clear reason to expect the epigenome to be disturbed in these disorders. Further, given the importance of the epigenome to neuronal development, we suspect that epigenetic disturbance may contribute to neurological disease. Our project will examine whether neuronal differentiation is dependent on the affected pathways, and whether disturbed epigenetic modifications contribute to neurological dysfunction in these disorders. To do so, we will use induced pluripotent stem cell (iPSC)-to-neuron differentiation in vitro. This will be used to develop a better understanding of whether epigenomic disturbances throughout neuronal development can help predict disease progression and improve clinical treatments. Further, using patient material, we will identify whether individuals with remethylation disorders have altered global and loci-specific epigenetic status, whether this varies between patients, and whether this correlates to the overall disease state.

Weiterführende Informationen

Lead

Dr. Sean Froese
Division of Metabolic Diseases
University Children's Hospital Zurich

Collaborator

Prof. Ferdinand von Meyenn
Department of Health Science and Technology, ETH Zurich