WHAT WE DO
All organisms must control when to turn on (express) or turn off (silence) specific genes according to their developmental stage and environmental conditions. There are many ways in which cells can control gene expression. The Transgenerational Brain Initiative is studying a gene regulatory process that can turn off a gene not only in an animal but also 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 study this method of transgenerational gene regulation using conditions that more closely match animal physiology. We are also creating a collection of different genes to test the more than 100 types of neurons in our model animal to determine which neurons are best able to control gene expression in the next generation of worms.
WHY IT MATTERS
In took 20 years since the discovery of RNA interference (RNAi) to the development of a new class of pharmaceutical based on small interfering RNAs. In August 2018, the first RNAi drug was approved by the FDA. This drug is a modified RNA that must travel through the circulatory system to the target 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
Students will learn basic skills and methods routinely used in biology research labs. They learn molecular biology techniques to create a fluorescent reporter gene using polymerase chain reaction (PCR) and restriction enzymes. We will use the CRISPR/Cas9 genome editing system to insert these reporter genes into the genome of our model animal, C. elegans.