Throughout the RIBOINFLAM project, we explored how cells regulate protein production during immune responses and viral infections. Our research focused on three key questions, leading to the following results:
1. How do ribosomes change during viral infections and immune responses?
During the project, we developed protocols to purify ribosomes in cultured cells and in vivo, allowing us to analyze how their composition changes in response to infections and immune activation. Using these protocols, we identified host cell factors that help or hinder viral replication. In addition, we explored how immune cells adjust their ribosomes when they are activated to fight infections, discovering unexpected factors with potential new roles in immune defense.
2. How does protein production influence the lifespan of genetic messages?
Cells do not uniquely synthesize mRNAs and proteins, they also break them down to maintain balance. Our research aimed to better understand how ribosomes influence the process of mRNA degradation. Scientists knew that translating an mRNA into a protein can also mark it for degradation, but the precise rules governing this were unclear. Using computational and molecular techniques to track how long different mRNAs survive we discovered that certain genetic features—such as how ribosomes interact with an mRNA, the length of regulatory regions, and the composition of genetic "words" (codons), determine how quickly an mRNA is degraded. We also found that translation regulates mRNA stability differently when T lymphocytes are activated, a discovery with potential implications for mRNA vaccine design.
3. How do two different protein-making systems work together in immune cells?
Our cells have two types of ribosomes: cytosolic ribosomes, which produce most cellular proteins, and mitochondrial ribosomes, which produce a small number of proteins essential for energy production. Although these two systems are separated, we explored whether they communicate and influence each other during immune responses. To investigate this, we created genetically modified mice in which mitochondrial ribosome function could be selectively turned off in specific immune cells as well as genetically modified mice in which mitochondrial ribosomes have been modified to include a “handle” that allows their easy purification to study their composition. Our experiments revealed that mitochondrial protein production is crucial for maintaining a special type of immune cell called "Virtual Memory" CD8+ T lymphocytes. We are now working to understand exactly how mitochondrial ribosomes support these cells.
Some of the above mentioned results have been published in peer-reviewed journals or patented, while others are currently being prepared for publications or are still in a preliminary phase, requiring additional research work before being submitted for publication. Finally, during the project, we continuously presented our results at conferences and invited seminars.
