Analysis of MLIV patient fibroblasts for contact dynamics and calcium uptake

Clinical Score: 0.850 Price: $0.50 mucolipidosis type IV human patient fibroblasts Status: proposed

What This Experiment Tests

Clinical experiment designed to assess clinical efficacy targeting MCOLN1 in human patient fibroblasts. Primary outcome: mitochondria-lysosome contact dynamics and calcium uptake defects

Description

Patient-derived fibroblasts from individuals with mucolipidosis type IV (MLIV) were analyzed to examine mitochondria-lysosome contact dynamics and contact-dependent mitochondrial calcium uptake. Since MLIV results from loss of TRPML1 function, these patient cells served as a disease model to validate the functional importance of TRPML1 in mitochondria-lysosome contact-mediated calcium transfer. The study compared contact site formation, stability, and calcium transfer efficiency between MLIV patient fibroblasts and control cells. This experiment aimed to demonstrate the pathophysiological relevance of the mitochondria-lysosome contact mechanism discovered in the primary cell biology experiments and to show how TRPML1 dysfunction in human disease affects these critical interorganelle interactions.

TARGET GENE
MODEL SYSTEM
human patient fibroblasts
ESTIMATED COST
$0
TIMELINE
0 months
PATHWAY
mitochondrial calcium signaling
SOURCE
extracted_from_pmid_32703809
PRIMARY OUTCOME
mitochondria-lysosome contact dynamics and calcium uptake defects

Scoring Dimensions

Info Gain 0.00 (25%) Feasibility 0.00 (20%) Hyp Coverage 0.00 (20%) Cost Effect. 0.00 (15%) Novelty 0.00 (10%) Ethical Safety 0.00 (10%) 0.850 composite

📖 Wiki Pages

MCOLN1 — Mucolipin-1 (TRPML1)geneMitochondriaentityExperimentsindexAMPK (AMP-Activated Protein Kinase)entityAMPK Agonist Therapy for NeurodegenerationideaLysosomal Calcium Dysregulation in NeurodegeneratimechanismMembrane Trafficking Pathway Dysfunction in Neurodmechanism

Protocol

comparison of patient vs control fibroblasts using live-cell microscopy and calcium imaging

Expected Outcomes

MLIV patient cells should show altered contact dynamics and defective calcium transfer

Success Criteria

measurable differences in contact formation and calcium uptake between patient and control cells

Related Hypotheses (1)

Lysosomal Calcium Channel Modulation Therapy0.697

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