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Master Thesis: Understanding the effect of toxic metabolites of a rare metabolic disorder in minibrains
Patients with the rare metabolic disorder argininosuccinate lyase deficiency (ASLD) often develop severe neurological outcomes. Our aims:
1. test the impact on brain of toxic metabolites specific to ASLD
2. test if creatine (Cr) has protective effects.
If proved, Cr could provide a novel co-therap
The aim of the project is to understand the pathophysiology of the neurological disease in argininosuccinate lyase deficiency (ASLD), a rare metabolic disorder, which often leads to severe neurological disease. ASLD patients accumulate ammonia (it’s effect in brain has been thoroughly studied) and other metabolites, which probably contribute to the neurological phenotype. Our goal is to understand the effect of these other metabolites in the developing brain and to test if creatine, currently used to treat neurodegenerative disorders, has protective effects. To do so, we will use a 3D in-vitro model of rat organotypic brain cell cultures in aggregates to mimic ASLD (this model is already set up in our laboratory), and we will analyse samples by metabolite analyses, immunohistochemistry, western blotting and metabolomics. In a pilot study, we have already obtained promising results. Thus, this project can be immediately started. The research team of Prof. Häberle are world experts in ASLD, and form part of a dynamic metabolic group at the University Children’s Hospital interested in understanding the molecular basis and developing novel treatments for ASLD and other rare metabolic disorders.
The aim of the project is to understand the pathophysiology of the neurological disease in argininosuccinate lyase deficiency (ASLD), a rare metabolic disorder, which often leads to severe neurological disease. ASLD patients accumulate ammonia (it’s effect in brain has been thoroughly studied) and other metabolites, which probably contribute to the neurological phenotype. Our goal is to understand the effect of these other metabolites in the developing brain and to test if creatine, currently used to treat neurodegenerative disorders, has protective effects. To do so, we will use a 3D in-vitro model of rat organotypic brain cell cultures in aggregates to mimic ASLD (this model is already set up in our laboratory), and we will analyse samples by metabolite analyses, immunohistochemistry, western blotting and metabolomics. In a pilot study, we have already obtained promising results. Thus, this project can be immediately started. The research team of Prof. Häberle are world experts in ASLD, and form part of a dynamic metabolic group at the University Children’s Hospital interested in understanding the molecular basis and developing novel treatments for ASLD and other rare metabolic disorders.
The aim of the project is to understand the pathophysiology of the neurological disease in argininosuccinate lyase deficiency (ASLD), a rare metabolic disorder, which often leads to severe neurological disease.
The aim of the project is to understand the pathophysiology of the neurological disease in argininosuccinate lyase deficiency (ASLD), a rare metabolic disorder, which often leads to severe neurological disease.
Dr. Carmen Diez at carmen.diez@kispi.uzh.ch or Prof. Johannes Häberle at Johannes.Haeberle@kispi.uzh.ch.
Dr. Carmen Diez at carmen.diez@kispi.uzh.ch or Prof. Johannes Häberle at Johannes.Haeberle@kispi.uzh.ch.