Implementing a model organism for studying vault function and application as smart adjuvant for fish vaccination.
Project lead: Michael Dondrup
Institution: University of Bergen
Partner: Geffen School of Medicine at UCLA
Funding: The Research Council of Norway within the FRIMEDBIO program
Duration: September 2019–August 2023
Inside your cells, and the cells of many other organisms, are a hundred thousand tiny structures with beautiful, cathedral-like scaffolds and hollow inner spaces called “vault organelles”. The function of these vaults is one of the last big enigmas of cell biology. Since their discovery in 1986, researchers have found evidence that vaults might be involved in drug resistance, cell signaling, and transporting molecules around the cell — but nobody knows for sure. Recently, a team of researchers in Bergen studying pesticide-resistance in the Atlantic salmon louse, a parasite of salmon, discovered that the lice genome also contains genes for vaults. This made the researchers wonder if the lice could be the key to beating resistances in both lice and cancers and unlocking the secret function of vaults. They started this new project called LiceVault to find out.
Salmon lice are parasites that feed on the blood of salmon. The Norwegian aquaculture industry spends five billion NOK each year fighting them with treatments like medicine, warm water, and using cleaner-fish.It was believed that salmon lice, like most arthropods, do not have vaults but researchers at LiceVault discovered that not only do they have vaults, their small genome contains four duplicates of the gene that codes for vaults. The high gene ratio and the louse’s co-evolution with pesticides makes them an ideal organism to apply cellular biology techniques to study the function of vaults.
Previous experiments suggested that cells produce more vaults when under stress. LiceVault will test if this is the source of their drug resistance by interfering with vault gene expression in louse larvae and measuring how that effects their resistance to commonly used pesticides. They have already identified several compounds that could overcome this resistance and help control the lice. Computational methods to model gene expression and understand the 3D structure of the vaults will aid the researchers in refining the structure of these molecules.
Researchers at LiceVault are using their contacts in the Norwegian fishing and aquaculture industry from their previous work at the Sea Lice Research Centre, to understand how vaults are connected to the lifestyle of the louse and the salmon they feed on. They will work with these stakeholders to create applications for their research and the data will be placed in a public data repository so other louse researchers can build on their work.
Each new discovery is a clue to understanding vault function. That basic research may translate into a more potent vaccine against salmon parasites and could eventually produce more effective cancer treatments. Solving the mystery of vault organelles will open the door to almost endless new translational research.