Epigenetics and network excitability related to autism and dementia
|Interdisciplinary Areas:||Data and Engineering Applications, Engineering-Medicine
Emerging studies have shown that epigenetic alternations underlie a wide range of neurological diseases spanning from neurodevelopmental disorders (e.g., autism) to neurodegenerative disorders (e.g., Alzheimer’s disease and other dementia). It is found that changes in epigenetic landscape, impaired neuronal excitability and activation of microglia could be convergent mechanisms of these otherwise very different diseases. Indeed, it is recently discovered that genetic mutations in a key epigenetic gene DNMT1, lead to devastating disease symptoms including dementia, neuropathy, and seizures of affect patients. However, the disease mechanisms are unknown. Yang lab and Yuan lab have established multiple mouse models, iPSCs derived neurons/organoids and microglia models to study the interactions of neurons and microglia underlying these disease phenotypes. Questions to be addressed includes: what’s the role of microglia in the maladaptation of altered firing of neurons? What are the neurons or microglia specific epigenetic changes that can be identified in the disease models? Can epigenetics factors by targeted to alleviate these diseases? Combining the expertise from both labs, cutting-edge technology including CRISPR mediated activator and inhibitors, single-cell RNA-sequencing and spatial transcriptomics, high-density in vitro and in vivo electrophysiology, optogenetics and chemogenetics will be used to tackle these questions
Ideal candidate should have a background in neuroscience, molecular biology, bioengineering or physiology. We welcome candidate who is motived to learn new skillsets, and is enthusiastic about multidisciplinary research.
Chongli Yuan, Davidson School of Chemical Engineering, https://engineering.purdue.edu/ChE/people/ptProfile?resource_id=65069
Yang Yang, Medicinal Chemistry and Molecular Pharmacology, https://www.yangyanglab.org/
Bill Skarnes, the Jackson Laboratory
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