Output Catalog
ASAP is committed to accelerating the pace of discovery and informing a path to a cure for Parkinson’s disease through collaboration, research-enabling resources, and data sharing. We created this catalog to showcase the research outputs and tools developed by ASAP-funded programs.
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An ImageJ/FIJI Preprocessing Workflow for Multi-Series Confocal Microscopy Datasets Prior To CellProfiler Analysis
A workflow using ImageJ/FIJI aims to create three-slice MIPs from multi-series .czi files to capture weak signals. It involves extracting datasets, creating projections, and saving images for efficient analysis in CellProfiler.
Extracellular space diffusion modelling identifies distinct functional advantages of archetypical glutamatergic and GABAergic synapse geometries
We modelled extracellular diffusion in super-resolved images of live brain tissue neuropil. We found that extracellular space geometry shapes local diffusion and this has functional implications for signaling arising from synaptic spill-over.
Protocol for efficient CRISPRi-mediated silencing of retrotransposons in human pluripotent stem cells
This methods paper outlines silencing transposable elements in hiPSCs using CRISPRi. Describes gRNA design, validation via multiome approach. Enables functional studies on TE transcription in hiPSC models.
A human lysosomal storage disorder toolkit for decoding proteome landscapes in cortical and dopaminergic-like induced neurons
Lysosomal Storage Disorders impact lysosomal function and can be linked to Parkinson's Disease risk. LSD mutant cells show varied endolysosomal proteomes, with specific disruptions in neuronal cells.
Elevated phosphorylated α-synuclein and phosphorylated tau in Lrrk2 p.G2019S-mutant mice following influenza A pneumonitis
Influenza virus infection does not alter acute sickness in mice with Lrrk2 mutations. Surviving Lrrk2 p.G2019S KI mice, however, had elevated oxidative stress and phosphorylated a-synuclein and tau proteins in their brains six weeks post-infection.
Robust analytical methods for bis(monoacylglycero)phosphate profiling in health and disease
BMP is a crucial phospholipid in lysosomes, impacting metabolic balance and linked to neurodegenerative diseases. LC-MS methods are detailed for accurate BMP analysis, utilizing structural differences and a new CLN5 function for profiling.
A CellProfiler Pipeline for Quantification of p-SNCA in Mouse Striatal Cholinergic and Medium Spiny Neurons V.2
Brain sections stained for pSNCA, DARPP-32, ChAT, and DAPI. Z-stacks processed into MIPs for analysis. Outputs include pSNCA intensity and neuronal mask area, normalised for cell type-specific burden using R script.
Selective loss of Primary Cilia and Neurotrophic Signaling in G51D α-Synuclein Mice Highlights a Common Pathway to Parkinson’s Disease
G51D α-synuclein mice mimic disease symptoms, showing cilia loss in specific neurons and impaired neurotrophic signaling, contributing to disease progression. This highlights the role of ciliary dysfunction in Parkinson’s.
Single cell eQTL mapping reveals convergent glial–neuronal risk architecture in Parkinson’s disease
Population-scale, disease-context aware meta single-nucleus eQTLs mapping (N = 1,197) in nine cell types from cortex and substantia nigra identifies 125 risk genes and cell types for PD GWAS signals.
CREsted: modeling genomic and synthetic cell-type-specific enhancers across tissues and species
CREsted, a sequence-based deep learning model, analyzes genomic regulatory code, decodes enhancer grammar, and designs synthetic enhancers. It preprocesses single-cell data, models chromatin accessibility, and compares cell states across tissues.
ATP13A4 gates extracellular polyamine levels to control excitatory synaptogenesis
Polyamines are crucial for brain function. ATP13A4 is the main polyamine transporter in astrocytes, impacting astrocyte morphology, synapse formation, and neurodevelopment. Mutations in ATP13A4 are linked to neurodevelopmental disorders.
State-dependent modulation of spiny projection neurons controls levodopa-induced dyskinesia in a mouse model of Parkinson’s disease
LID is poorly understood, our research on dyskinetic mice show SPNs' properties oscillate during LID and are influenced by dopamine and acetylcholine signaling. Targeting M1 receptors in iSPNs reduced LID severity and improved levodopa effects.
T cell purification and activation
This protocol details the purification and activation of Mouse Naïve CD8+ T Cell from mouse spleen
Activation of transposable elements is linked to a region- and cell-type-specific interferon response in Parkinson’s disease
Study explores transposable elements role in Parkinson's disease neuroinflammation. TE activation in specific brain regions correlates with innate immune responses, indicating potential involvement in chronic neuroinflammation and PD progression.
Cell-type-resolved somatic variant discovery from bulk long-read sequencing
SniffCell uses DNA methylation on long reads to assign somatic variants to specific cell types, enabling cell-type-resolved variant discovery and revealing recurrent neuron-specific tandem-repeat expansions in human tissues.
