Partnership Opportunities

Systems Biology to Study Peroxisomal Diseases

Applying a systems approach to the molecular mechanisms of rare diseases

Technology overview

John Aitchison        Dr. John Aitchison

Dr. Aitchison and his team have a long-standing interest in the basic biology of peroxisomes. These eukaryotic cell organelles are essential for metabolizing lipids and neutralizing damaging oxidizing agents. Defects in peroxisomal function are linked to aging as well as to diabetes, obesity, metabolic syndrome, and cancer.

Inherited defects in genes required for peroxisomal formation and activity result in neuropathologies such as infantile Refsum disease, neonatal adrenoleukodystrophy, and Zellweger spectrum disorders. Similar to mitochondrial myopathies, children with these rare inherited peroxisomal diseases may have low muscle tone, hearing or vision difficulties, and seizures. Progression is often rapid, with death occurring in infancy or childhood.

The Aitchison group is applying a comprehensive, systems biology approach to studying peroxisomes. The lab can carry out wet-lab purification of organelles and cell complexes as well as high-throughput analyses by transcriptomic, proteomic, and metabolomic techniques. The group also develops computational methods that incorporate these diverse data sources to model cellular processes. The scientists often use yeast as a model organism because it grows easily and rapidly, and the genes involved in generating and maintaining peroxisomes have homologs in the human genome.

Results from this research are providing a fundamental understanding of the genetics, functions, regulation, and dynamics of peroxisomes. The findings are identifying drug and treatment targets for the rare peroxisomal diseases. The methods from the Aitchison group can also be applied to other cellular structures and processes to learn about human health issues from inherited to infectious diseases and from chronic to acute conditions.

Stage of Development

  • Preclinical in vitro

Partnering Opportunities

  • Collaborative research opportunity
  • Sponsored research agreement
  • Consultation agreement

Publications

  1. Mast FD, Herricks T, Strehler KM, Miller LR, Saleem RA, Rachubinski RA, Aitchison JD. ESCRT-III is required for scissioning new peroxisomes from the endoplasmic reticulum. J Cell Biol. 2018;217:2087-2102.
  2. Mast FD, Jamakhandi A, Saleem RA, Dilworth DJ, Rogers RS, Rachubinski RA, Aitchison JD. Peroxins Pex30 and Pex29 dynamically associate with reticulons to regulate peroxisome biogenesis from the endoplasmic reticulum. J Biol Chem. 2016;291:15408-15427.
  3. Mast FD, Rachubinski RA, Aitchison JD. Signaling dynamics and peroxisomes. Curr Opinion Cell Biol. 2015;35:131-136.

Learn more

To learn more about partnering with Seattle Children’s Research Institute on this or other projects, email the Office of Science-Industry Partnerships.