Principal Investigator, Chair in Biochemistry
Prof. Dr. Günter Schwarz and his team are investigating metabolic disorders, focusing on molybdenum cofactor deficiency. Using biotechnology to produce a precursor of molybdenum cofactor, the team has developed a treatment for this inborn error of metabolism. They are also focusing on mechanisms of synaptogenesis and its function in the pathogenesis of epilepsy. In addition, they are trying to ascertain how changes in metabolism cause Huntington’s disease.
Our research: Research by Prof. Schwarz’s team focuses on two areas. First, the scientists are investigating metabolic disorders such as molybdenum cofactor deficiency, an autosomal recessive disease which presents in neonates with severe seizures that are difficult to treat. The second focus is on neurodegenerative processes, for example, the mechanisms of synaptogenesis and their function in the development of epilepsy.
Our successes: The development of treatment for children with molybdenum cofactor deficiency is one of the group’s great successes to date. In the past, these patients could only be treated symptomatically and died in early childhood. Compassionate use of a precursor of molybdenum cofactor, produced in bacteria, has now been successfully used in several patients. Results of this study were accepted for publication in the high-impact journal The Lancet. In their research into neurodegenerative disorders, the scientists have discovered new mechanisms of synaptogenesis in inhibitory neurons. The group also identified a new nitric oxide synthase in mitochondria and is looking now at its function in the nitrite-dependent regulation of blood pressure. In 2010, Prof. Schwarz was awarded the North Rhine-Westfalia Prize for Innovation.
Our goals: The aim of the neurobiological research carried out by the team is to understand which biochemical/molecular processes regulate the formation and elimination of inhibitory synapses. A further aim is to investigate how altered sulfur metabolism impacts the pathogenesis of various diseases. Conditions such as Huntington’s disease have been associated with cysteine degradation, as has longevity.
Our methods/techniques: The Schwarz laboratory combines protein biochemistry techniques with methods used in cell and structural biology. Relevant metabolic processes are investigated in proteins, structural or functional changes are analyzed in cell cultures, usually neurons, and the effects of these changes on the morphology of synapses and neuronal development are further observed and verified in various animal models.
Figure 1: Magenetic resonance images of a molybdenum cofactor deficient patient recorded at an age of 12 and 27 days showing rapidly progressing brain damage resulting in brain atrophy and cystic changes in the cerebral cortex.
Figure 2: Model for palmitoylation-mediated regulation of gephyrin clustering and plasticity. Gephyrin is palmitoylated by the palmitoyl transferase DHHC-12, which localized to Golgi outposts in primary dendritic shafts. At the synapse, palmitoylated gephyrin stabilizes GABA type A receptors. Silencing of GABAergic transmission leads to gephyrin depalmitoylation via gephyrin nitrosylation, membrane release, and decrease in cluster size.