Drug modulation of microglia to treat neurodegenerative and neurodevelopmental disorders
Microglia are CNS-privileged innate immune cells deeply implicated in the etiology of Alzheimer’s disease (AD), frontal temporal dementia and Parkinson’s. They are responsible for rapid immune response to pathogens and molecular patterns of danger; changing their transcription profile to enact an aggressive phagoctyic response accompanied by massive oxidative bursts and release of pro-
inflammatory cytokines. In AD, microglia become increasingly inefficient in their response to accumulating toxins in the AD brain and while stuck in a long-term dysregulated state contribute to neuronal loss in the decades between onset of pathology and dementia. Receptors that modulate their action are now the most targeted genes by the pharmaceutical industry in AD therapeutic development with potential applications in the treatment traumatic brain injury, schizophrenia, and Parkinsons’s disease.
We are looking for students to work on discovery of small-drug and biologic inhibitors of a human microglial receptor. The work is designed to teach the drug discovery process from target rationale, bioinformatics, receptor production, ligand screening and functional studies that constitute a contemporary drug discovery campaign not exclusive to neurological disorders. An interest in neurodegeneration or innate immunity would be valuable.
Dr Leah Beauchamp