RNA interference (RNAi) was a relatively new technology when Thomas Tuschl began tinkering with it. RNAi interested Tuschl and others because it presented a new way to silence genes. Tuschl recognized, however, that RNAi, originally developed in the nematode C. elegans, needed some tweaking before it could be employed in mammalian cells. Thanks to his savvy manipulations, which made RNAi work in mammalian cells, thousands of labs worldwide are now using the technique to investigate the function of individual genes.

Considered one of the leaders in this new revolution in mammalian genetics, Tuschl approaches biological problems with a chemist's rigor. He is now studying the regulatory functions of RNA. These include RNA interference, the control of protein synthesis by small bits of RNA known as microRNA (miRNA)—which were discovered by Tuschl, and RNA-guided modifications to the material of the chromosomes, called chromatin. This remodeling of the chromatin makes genes accessible to the cellular components that copy them to the messenger RNA needed to guide protein synthesis.

One of Tuschl's current projects involves developing sensitive techniques to detect where and when cells express miRNAs, which is difficult to determine because of those molecules' small size. He is also studying the biological functions of miRNAs, which are currently unknown for the vast majority of the several hundred mammalian miRNAs.

He and his colleagues are also identifying the miRNAs that human cells express at specific stages of development and in specific tissues, which may be associated with diseases such as cancer. He has discovered that certain viruses also express miRNA, which they use to manipulate host and viral genes. Studies of the targets of these viral miRNAs could enhance understanding of host-virus interactions.

Tuschl is also exploring the links between RNA silencing and genetic disorders such as fragile X syndrome, the most common genetic cause of mental impairment, as well as certain cancers.