Research team
From Tear Drops to Diagnostics: Profiling Tear RNA for Early Biomarker Discovery in Alzheimer's Disease.
Abstract
The rising prevalence of Alzheimer's disease (AD) increasingly demands faster and unambiguous diagnosis. Due to their developmental and physical relatedness to the brain, tear fluid presents itself as an ideal non-invasive biomarker candidate. Although the tears' RNA content could fill this dire biomarker gap, they remain surprisingly underexploited. Therefore, this project aims to tackle this unmet need by mapping the total RNA content of tear fluid and employing these results to detect improved early AD biomarkers. We hypothesize that tear fluid offers a unique, non-invasive view into the brain and that the RNA within these tears provides signs of early AD and other neurodegenerative disorders that can be employed as a future non-invasive biomarker. This project builds on the expansive experience of the promoter in RNA analysis and on the AD expertise of the Sleegers Lab at VIB-CMN. In Task 1, we will extract and sequence the RNA of tears from 100 elders who are included in a separate longitudinal study. In Task 2, we will analyze these samples' circular RNA and linear RNA content and find transcriptomic differences related to dementia risk factors, genetic risk scores, and cognitive test scores. This project will (1) develop a new tool for sequencing the total tear-derived transcriptome, (2) provide the first line of evidence for phenotype-induced changes in the tear RNA, and (3) generate unique datasets ready for valorization. In its role as a seed project, the granting of this proposal would carve out a unique niche to kick-start the promoter's career and initiate a promising line of up-and-coming research in the lab.Researcher(s)
- Promoter: Verwilt Jasper
Research team(s)
Project type(s)
- Research Project
Discovering novel RNA and DNA biomarkers for non-invasive liquid biopsy-based diagnosis of Alzheimer's disease through innovative long-read sequencing approaches.
Abstract
The rising prevalence of Alzheimer's disease (AD) increasingly demands faster, more accurate non-invasive diagnosis. Although extracellular nucleic acids can fill this gap as prime biomarker candidates, they remain surprisingly underexploited. Therefore, this project aims to tackle this unmet need by mapping the extracellular RNA (exRNA) and DNA content of non-invasive liquid biopsies and employ these results to detect improved AD biomarkers. I hypothesize that AD patients' biofluids reflect transcriptional and epigenetic alterations in their brains and that we can use those changes to improve AD diagnosis. This project builds on my expansive experience in long-read exRNA sequencing and the expertise on AD of the Sleegers Lab at VIB-CMN. In WP1, I will develop a novel long-read sequencing method for total exRNA sequencing and apply it to case-control AD blood plasma, CSF, urine, and tear fluid. In WP2, I will determine differentially abundant circRNA in the AD liquid biopsies and establish their complete sequence. Finally, in WP3, I will sequence the extracellular epigenome of these biofluids and discover AD-specific methylation signatures. This project will (1) develop innovative tools to analyze exRNA; (2) present the first evidence for non-invasive linear RNA, circRNA, and DNA AD biomarkers; and (3) generate unique datasets ready for valorization. In the future, this will drive novel discoveries on AD's inner workings and translate toward its early, unambiguous diagnosis.Researcher(s)
- Promoter: Sleegers Kristel
- Fellow: Verwilt Jasper
Research team(s)
Project type(s)
- Research Project