Periodic Reporting for period 4 - PeroxiSystem (Systematic exploration of peroxisomal structure and function)
Reporting period: 2020-03-01 to 2020-08-31
Additionally a large number of peroxisomal disorders with dramatic phenotypes have been described and malfunctions in peroxisomes contribute to the etiology of Alzheimer's and Parkinson's diseases, aging, cancer and type 2 diabetes.
We are using systems cell biology approaches in yeast in an attempt to understand peroxisomes as a complete biological system.
We are specifically interested in:
Identifying new functions of peroxisomes
Discovering new peroxisomal proteins
Identifying peroxisome contact sites with other organelles
Systematically characterizing the peroxisome proteome under different conditions
Further understanding how proteins are targeted to peroxisomes
Identifying the peroxisomal protein quality control machinery
1. Discover many new peroxisomal proteins never before studied
2. Uncover a function for many new peroxisomal proteins
3. Demonstrate that there are subpopulations of peroxisomes in cells
4. Discover a new targeting pathway to peroxisomes (Pex9) and the rules governing substrate selectivity for this pathway
5. Create a whole organelle peroxisome protein-protein interaction map
6. Create mini peroxisome libraries with mutants in all peroxisomal proteins to enable rapid characterization of new peroxisomal proteins.
7. Create a new tool to study contact sites
8. Define the "gold standard" criteria for experimentally defining a contact site tether
9. Uncover all peroxisomal contact sites and name them
10. Find two new contact site tethers for the peroxisome-mitochondria contact
11. Describe the function of the peroxisome-mitochondria contact
In addition, we have made a unique tool for the entire yeast cell biology community that should revolutionize the exploration of gene functions (the SWAT approach). We also wrote several (4) reviews and an opinion piece intended to summarize the field and explore new hypotheses and ideas. We have also created a free online database for use by all researchers in the field of cell biology that should enable exploration of gene functions (dHITS).