Impaired mitochondrial energy metabolism is recognized as an increasingly relevant cause of human disability in Europe, especially for infants and children.
Besides mutations in the mitochondrial genome, mitochondrial disorders can be the consequence of mutations in numerous nuclear genes encoding factors involved in mtDNA maintenance and expression, and in the formation and regulation of the mitochondrial respiratory chain (MRC). In particular, mutations in genes encoding factors controlling the assembly o f MRC are responsible for severe, early-onset mitochondrial syndromes.
However, in spite of the wealth of information gathered in recent years on the genetic basis of these disorders, neither the detailed molecular mechanisms leading to cell or tissue failure are known, nor are the metabolic consequences ultimately determining the clinical phenotype, completely understood.
The aim of this project is to allow Dr. Erika Fernandez-Vizarra, a researcher with experience in Biochemistry and Molecular and Cellular Biology, to undertake training through research at the Istituto Nazionale Neurologico Carlo Besta in Milan, Italy, with a view to completing her expertise in the mechanisms of formation, structural modulation and functional control of MRC and mitochondria l homeostasis.
In collaboration with the host, she will shed light on the normal function of, and pathogenic mechanisms due to mutations in three disease-associated MRC assembly factors, Surf1, BCS1L and COX15.
The project will be implemented via a multidisciplinary approach including in vitro characterization of mitochondrial proteins, cell biology and cell imaging on normal and mutant cell lines, and in vivo studies based on the creation and investigation of recombinant animals.
Fields of science
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