Discovery and manipulation of key regulators of cell identity in the brain through cellular reprogramming and CRISPR

Supervisors: Prof. Dr. Stefan Stricker & Prof. Dr. Magdalena Götz

Enrolled since 2020

Cell specification is a fundamental aspect of various developmental processes. An intriguing example for this process is neurodevelopment, in which neural circuits are fine-tuned in a functional and temporal manner. To uphold the seamless operation of the intricate brain network, predominantly composed of neurons and glial cells, each element must perform its specific role with precision. In the case of astrocytes, the most abundant glial cells in the brain, one single cell type holds a multitude of functions. They regulate processes such as synaptogenesis, neurotransmitter regulation, and neuroprotection. Recognizing the significance of astrocytes in both normal brain function and pathology, our research focuses on unraveling key regulators governing astrocytic cell identity. By employing state-of-the-art technologies, specifically CRISPR Cas9, we aim to manipulate the astrocyte identity in the context of cell replacement therapy. Additionally, utilizing induced pluripotent stem cell (iPSC)-derived cells, we are able to challenge human astrocyte cell identity. This interdisciplinary approach, combining cellular reprogramming and genome editing, holds promise in uncovering novel therapeutic strategies targeting traumatic brain injuries and neurodegenerative diseases.

Publications

  • Roman C et al., Astrocytic-neuronal crosstalk gets jammed: Alternative perspectives on the onset of neuropsychiatric disorders. Eur J Neurosci. 2021;54(5):5717-5729.
  • Zander A et al., Guide-independent DNA cleavage by archaeal Argonaute from Methanocaldococcusjannaschii. Nat Microbiol. 2017 Mar 20;2:17034.