In the Jagtap Lab, we delve into the intricate world of protein-RNA complexes involved in human health and diseases. The current focus is on RNA helicases, essential enzymes that unwind cellular RNAs, driving numerous cellular processes. While their dysregulation is implicated in a range of human diseases, developing targeted drugs remains a significant challenge due to their shared ATP and RNA binding sites with other cellular proteins.

 

We are tackling this challenge head-on by investigating regulation in these helicases to find new, transient drug binding sites. For this, we focus on a specific subset of auxiliary domains called RNA binding domains (RBDs) within these vital enzymes. Building on our recent breakthrough in understanding the role of RBDs in switching ON or OFF the function of the RNA helicase MLE, we hypothesise that similar regulatory principles are conserved across other helicases containing these accessory domains.

 

Our multidisciplinary approach, integrating structural, biochemical, and cellular studies, aims to:

• Understand how auxiliary RBDs influence helicase functions.

• Identify changes in their RNA targets upon changing dynamic regulation by RBDs .

• Explore how RBD regulation alters the protein network of these helicases.

 

We are actively seeking to discover small-molecule modulators that can precisely target dysregulated RNA helicases. Our ultimate goal is to translate our fundamental understanding of these helicases into innovative therapeutic strategies for diseases associated with their dysfunction, thereby advancing human health.

 

Through collaborative efforts and cutting-edge methodologies, we are committed to uncovering the fundamental principles governing RNA helicase regulation and their far-reaching implications in human health and diseases!