ALZHEIMERS RESEARCH PROJECT: RNA Transport and Local Translation in Alzheimer's and Related Dementias (ADRD)

National Institute On Aging

Investigators

Abstract

We will use the iPSC Neurodegenerative Diseases Initiative (iNDI) cell lines and harmonize mRNA localization and local translation datasets with datasets generated through that initiative. As a pilot project, we knocked down RBPs using CRISPRi and performed transcriptomics and proteomics on fractionated axons. The CARD Advanced Analytics team generated pipelines for data analysis based on this pilot project, that we will move forward to the full analysis on the iNDI lines. This pilot project was recently published. Work is ongoing to characterize the effect of FTD/ALS mutations on mRNA transport and local translation in the iNDI lines. We have obtained RNA sequencing data for about half of the planned mutations and another 1/3 are in process, the remaining 1/3 of cell lines are not yet available. Data analysis is ongoing using pipelines from the pilot project with modifications for the increased complexity in the data due to increased sample number and batching. Additionally, work is in process to characterize the local transcriptome in the parental cell line, to identify the most impactful experiments to test for changes due to FTD/ALS mutations. We are also optimizing image analysis pipelines for upcoming microscopy experiments. As data is analyzed and new code generated, these resources will be made available to the neurodegenerative disease research community.