PD Functional Genomics | 2020
Understanding Inherited and Acquired Genetic Variation in Parkinson’s Disease through Single-Cell Multi-omics Analyses: A Unique Data Resource
Study Rationale: Parkinson’s disease (PD) is a disorder that not only affects the function of the brain, but also of the gut, which are both complex tissues composed of functionally diverse types of cells that need to cooperate for organ function. Around 90 regions of the DNA that we inherit from our parents, show differences between people with and without PD. Furthermore, as we develop and age, new, non-inherited DNA mutations may also be acquired in part of our body cells. How such inherited and newly acquired DNA variants function in increasing the risk of developing PD remains however largely unknown.
Hypothesis: Team Voet hypothesizes that these DNA variants can increase or decrease the activity of key (un)known genes in particular types of cells of the brain and the gut, which in turn increases the risk of developing PD.
Study Design: Team Voet will use the expertise of their consortium in analyzing single cells to study the brain and gut from individuals who lived with and without PD. Specifically, gene expression profiling of over 4,500,000 single cells will allow the team to discover the genes of which the expression is altered by the DNA variants, and importantly, also in which type of brain and/or gut cells the expression of the gene is disturbed. Team Voet will next analyze how these DNA variants change the functioning of these specific cell types, by using their existing models of the fruitfly, and of cultured human nerve and immune gut cells.
Impact on Diagnosis/Treatment of Parkinson’s Disease: This study will provide crucial mechanistic insights into how faults in our DNA change the functioning of specific cells in our brains and guts, and thus cause a predisposition to PD.
Leadership
Project Outcomes
By disclosing the Parkinson's disease (PD)-relevant genes and cell (sub)types in the brain and gut, and the molecular mechanisms of their gene expression (dys)regulation in the normal condition, with aging and in PD, Team Voet will advance their understanding of the etiopathogenesis of the disease and pave the path for devising new treatment modalities. View Team Outcomes.
Team Outputs
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Overall Contributions
Here is an overview of how this team’s article findings have contributed to the PD field as of November 2023. There are two different categorizations of these contributions – one by impact to the PD community and a second by scientific theme.
Impact
Theme
Featured Output
Below is an example of a research output from the team that contributes to the ASAP mission of accelerating discoveries for PD.
Nova-ST: Nano-Patterned Ultra-Dense platform for spatial transcriptomics
Spatial transcriptomics workflows using barcoded capture arrays are commonly used for resolving gene expression in tissues. However, existing techniques are either limited by capture array density or are cost-prohibitive for large-scale atlasing. Nova-ST, a dense nano-patterned spatial transcriptomics technique derived from randomly barcoded Illumina sequencing flow cells, enables customized, low-cost, flexible, and high-resolution spatial profiling of large tissue sections. Benchmarking on mouse brain sections demonstrates significantly higher sensitivity compared to existing methods, at reduced cost.
Team Accolades
Members of the team have been recognized for their contributions.
- Open Science Champions: Stein Aerts Lab, Thierry Voet, Florian De Rop, Shinjini Mukherjee, Bernard Thienpont
- Network Spotlights: Sara Salama, Zane Jaunmuktane, Ester Kalef-Ezra
- Awards
- COSA 2022: Natalie Kaempf (Reviewers Second Place Prize Winner)
Other Team Activities
- Working Groups:
- Single Cell Multi(Omics) – Thierry Voet (Co-Chair), Stein Aerts (Subgroup Lead)
- 10X Genomics Steering Committee – Thierry Voet (Chair)
- ANALYSE Neuropathology – Thomas Warner (Co-Chair)
- Interest Groups: Sequencing/Omics – Thierry Voet (Co-Chair)
In the News
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