Research
What we do
We ask fundamental questions about how the cell organizes gene expression.
We are particularly interested in biomolecular condensates, a class of membraneless cellular compartments that concentrate factors involved in nearly every step of RNA metabolism, from transcription to decay. Condensates include some of the oldest cellular landmarks identified by the first modern light microscopes— including the nucleolus, identified in the early 1800s, and the Cajal body, named for Santiago Ramón y Cajal who first described them as dense structures in neurons. However, despite the long history of their study, defining the functional role of condensates has remained exceptionally challenging.
Our understanding of biomolecular condensates was transformed in the last decade by the discovery that many may form through biological phase transitions— providing a new paradigm for intracellular organization. Phase transitions are often driven by low-affinity, multivalent interactions between nucleic acids and proteins, many of which contain intrinsically disordered regions. The dynamic nature of these interactions gives rise to an array of fascinating emergent features. We are particularly interested in the distinctively dynamic biophysical features of condensates, which can manifest across scales: from the dynamic exchange of molecules within and at condensate surfaces, to the mesoscale material properties of a condensate as a whole. We want to understanding the principles that give rise to these dynamic features and, importantly, how the biophysical features of condensates influence their molecular function.
For an intro to phase transitions, please visit this wonderful overview by Janet Iwata’s lab, University of Utah.
Why we do it
We are basic scientists that believe fundamental discoveries are essential for promoting human health.
While we are motivated by understanding fundamental questions about biomolecular condensate function, we also know that understanding these basic mechanisms is critical to uncovering those that drive disease. It has long been observed that condensates are disrupted in degenerative diseases and cancers, but their contribution to pathogenesis is poorly defined.
We hope that by better understanding the form and function of condensates in homeostasis, we will illuminate novel vulnerabilities in disease.
How we do it
We adapt our toolbox to our question.
We believe that the study of condensate function is fundamentally one that spans scales and disciplines. Therefore, we take an interdisciplinary approach including structural biology, biochemistry, molecular and systems cell biology to mechanistically uncover how biomolecular condensates and their assembly features influence RNA metabolism in the cell. We embrace tool-building for the purpose of better addressing our biological question. And we are always looking for avenues to collaborate!