Computational Biology & Genomic Initiatives
Documentation for active research projects, simulation studies, and variant reasoning models. All project output includes explicit evidence classification.
NPC1 Cholesterol Transport Dynamics & Lysosomal Trafficking
Computational modeling of sterol sensing domain mutations in Niemann-Pick disease type C1.
Niemann-Pick C1 (NPC1) is a 13-pass transmembrane lysosomal membrane protein essential for intracellular cholesterol export. Mutations in NPC1 lead to lysosomal lipid accumulation and progressive neurodegeneration. This project investigates variant-level conformational shifts using molecular dynamics simulations and machine learning residue contact graphs.
“How do missense variants in the sterol-sensing domain alter cholesterol transfer kinetics between NPC2 and NPC1?”
Variant-Level Biological Reasoning & Annotation Engine
Combining evolutionary protein embeddings with metabolic network topologies for rare disease variant scoring.
Standard variant effect predictors rely heavily on sequence conservation. This initiative integrates tissue-specific gene expression networks and protein structural dynamics to improve biological interpretability for unclassified variants (VUS).
“Can structural contact graph features resolve ambiguous VUS designations in lysosomal storage disorder genes?”
Computational Pathway Flux & Organelle Homeostasis
Systems-level dynamic ODE modeling of lysosomal lipid recycling.
Simulating whole-organelle lipid fluxes to determine how disruption in single transporters cascades into cellular stress responses, autophagy inhibition, and mitochondrial dysfunction.
“At what critical threshold of cholesterol accumulation does lysosomal membrane permeabilization trigger cell death pathways?”