WHAT WE DO
All organisms must control when to turn on (express) or turn off (silence) specific genes over their lifetimes as they grow and respond to changes in their environment. The Transgenerational Brain Initiative (TBI) studies a recently discovered gene regulatory process that can turn off a gene because of an RNA made in neurons. These neuronal RNAs can alter the genes expressed in the animal and in its offspring for multiple generations. The previous work on this phenomenon used older methods that have severe limitations. FIRE-TBI will use the latest methods of CRISPR/Cas9 genome editing to better examine this method of transgenerational gene regulation using conditions that more closely match animal physiology. We are also creating a collection of genes to test more than 100 types of neurons in our model animal to determine which neurons are best able to control gene expression in future generations.
WHY IT MATTERS
In August 2018, just 20 years since the discovery of RNA interference (RNAi), a new class of pharmaceuticals based on RNAi was approved by the FDA. This drug is a modified RNA that must travel through the circulatory system to cells in the liver. What we learn from how an animal synthesizes double-stranded RNA (dsRNA), processes dsRNA for export and how the dsRNA moves from one cell to a distant recipient cell could reveal clues that can be used to further improve RNAi-based therapies.
WHAT YOU LEARN
Our students learn the basic skills and methods routinely used in biology research labs such as polymerase chain reaction (PCR) and molecular cloning with restriction enzymes. They use these skills to create a fluorescent reporter gene to insert into our model animal, C. elegans. Students who return to be peer research mentors learn advanced techniques such as Gibson assembly, CRISPR/Cas9 genome editing and fluorescence microscopy to create and study our mutant worms.