Genetic mutations causing neurodegenerative diseases remain silent for decades before disease develops. How does the brain resist the toxic protein for so long and why do these mechanisms eventually fail?
To address these questions we developed a transgenic mouse line dubbed Tagger (Kaczmarczyk, et al., 2019) to study neuron-specific changes of gene expression at multiple levels of control. We will apply Tagger to knock-in mouse models of Huntington’s and other neurodegenerative diseases to study their mechanisms. We are also planning to extend the Tagger functionalities to other animal models using CRISPR/Cas9 technology.
You will embark on a project combining cell type-specific capture of translating mRNAs (Ribo-Tag) with SH-linked alkylation and metabolic labeling of RNA sequencing (SLAMseq) using Tagger. Established techniques will be used to expand our recent surprising findings using Ribo-Tag in the context of acquired neurodegenerative disease (scrapie). You will also participate in developing new models.
You will have access to cutting edge infrastructure including two Illumina RNA sequencers and multiple core facilities (FACS, microscopy, bioinformatics). Previous experience with RNA immunoprecipitation, nucleic acid analysis techniques and Next Generation Sequencing is required. Previous experience with CRISPR-Cas9 tools and/or bioinformatic skills in analyzing NGS data will be an asset, but are not required.