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ERC Starting Grant - Unraveling the mystery of preferential degeneration of midbrain neurons in neurodegerative diseases (oxDOPAMINE)

  • Project leader: Prof. Dr. Lena Burbulla
  • Affiliation: Biomedical Center (BMC)
  • Funding: 2021 to 2026

Over 200,000 people in Germany suffer from Parkinson’s disease, a progressive movement disorder that is characterized by the specific loss of nerve cells that synthesize the neurotransmitter dopamine. The absence of dopamine results in an involuntary tremor and sluggish execution of voluntary movements. Starting from skin biopsy samples obtained from Parkinson patients, Lena Burbulla and her colleagues generated induced pluripotent stem cells and differentiated them into dopamine-producing nerve cells in culture. She went on to show that oxidative stress in patient neurons initiates a pathological cascade of events that primarily affects the functions of mitochondria (the “energy powerhouses” of the cell) and lysosomes (the waste disposal and recycling system of the cell). Over time, oxidized versions of dopamine accumulate further exacerbating this toxic cascade.

In her ERC project entitled “Unraveling the Mystery of Preferential Degeneration of Midbrain Neurons in Neurodegenerative Diseases” (acronym: oxDOPAMINE), Burbulla will attempt to determine why cells in the midbrain in humans are particularly prone to accumulate oxidized dopamine, and hence susceptible to degeneration. Her working hypothesis is that defective dopamine metabolism at the synapses (which transmit nerve impulses), in association with a perturbation of iron metabolism, plays a critical role in this vicious circle. To explore this idea further, she also intends to investigate other, rarer neurodegenerative disorders in which defects in iron metabolism are involved.

Lena Burbulla studied Biology at LMU and earned her PhD at Tübingen University. She then worked as a postdoctoral fellow at Harvard Medical School, and in the Departments of Neurology at Massachusetts General Hospital in Boston and the Feinberg School of Medicine at Northwestern University in Chicago, where she is currently working as Assistant Professor. She was recently awarded a Heisenberg Grant funded by the Deutsche Forschungsgemeinschaft (DFG) and will soon join the SyNergy Cluster of Excellence at LMU, where her ERC project will be carried out.

Source: LMU