Julius Lucks Unraveling the RNA sequence/structure/function code for biology, medicine, & biotechnology

Research Interests

The Lucks Group is interested in unraveling the design principles that underlie the relationship between the sequence, structure and function of RNA molecules. Once thought to be a passive carrier of genetic information, RNAs are now understood to be essential for regulating and defending the genomes of all organisms. This broad array of function is hypothesized to be mediated by specific RNA structures that selectively interact with the molecular machines of the cell. It is our goal to understand and design these structures so that we may more deeply understand how RNAs fold and function in living systems, and to use this knowledge to engineer biomolecular systems as solutions to challenging problems in biology, medicine and biotechnology.

A major theme in the laboratory is to develop technologies called SHAPE-Seq that can characterize RNA structures in massively high throughput using next generation sequencing. This technology in turn opens new doors through which we can ask fundamental biological questions such as how specific RNA structures mediate cellular processes. Of particular recent interest is our study of how RNA molecules fold as they are being synthesized in the cell (co-transcriptional folding). With SHAPE-Seq we have recently been able to characterize the folding of an RNA molecule exiting actively transcribing RNA polymerase at nucleotide resolution for the first time. This is affording us unprecedented insights into how natural RNAs perform their function. For example, we have recently been able to uncover how riboswitches ‘make regulatory decisions’ in response to specific ligands. With these fundamental investigations, we also learn new RNA design principles that then feed back into our engineering methodology. Of particular interest is how we can learn new rules for RNA design that can be used to create a new class of molecular smart diagnostics to cheaply and quickly assess water quality in diverse settings.

Selected Publications

Elements of RNA Design. Carlson PD and Lucks JB. Biochemistry. 2019 March 19;58(11):1457-1459.

High-throughput determination of RNA structures. Strobel EJ, Yu AM, and Lucks JB. Nature Reviews Genetics. 2018 October;19(10):615-634.

Cotranscriptional folding of a riboswitch at nucleotide resolution. Watters KE, Strobel EJ, Yu AM, Lis JT, and Lucks JB. Nature Structural & Molecular Biology. 2016 December;23(12):1124-1131

Using in-cell SHAPE-Seq and simulations to probe structure–function design principles of RNA transcriptional regulators. Takahashi MK, Watters KE, Gasper PM, Abbott TR, Carlson PD, Chen AA, and Lucks JB. RNA. 2016 June;22(6):920-933.

Simultaneous characterization of cellular RNA structure and function with in-cell SHAPE-Seq. Watters KE, Abbott TR, and Lucks JB. Nucleic Acids Research. 2016 January 29;44(2):e12.

View all publications by Julius B. Lucks in the National Library of Medicine (PubMed).