Title: Decoding Intracellular Organization by Biomolecular Condensation

Abstract: The precise organization of biochemical functions in time and space is essential for cellular life. Intracellular organization is facilitated by the division of biomolecules into subcellular organelles. While classical organelles employ a lipid bilayer membrane to separate materials from the surrounding environment, an emerging class of organelles called biomolecular condensates do not utilize a delimiting membrane. Rather, multivalent interactions among proteins and nucleic acids drive the formation of concentrated, dynamic assemblies. Condensates regulate diverse cellular processes from transcription to signaling, and pathological condensates contribute to cancer and neurodegeneration. The physiological and pathological functions of condensates depend on key physical parameters such as size, subcellular location, and biomolecular composition. However, the mechanisms that control condensate properties and prevent the mixing of functionally distinct condensates remain largely unclear. My work examines how fundamental geometric and physical constraints in cells are exploited to control condensate form and function. In particular, I examine the impacts of restricting condensates to two different kinds of surfaces: lipid bilayer membranes and long noncoding RNA molecules. In this seminar, I will share two stories from my research on how both types of surfaces provide control over condensate size, position, and composition. Given the growing recognition that condensates associate with biological surfaces in diverse contexts, these studies reveal broadly applicable mechanisms for the control of condensate properties. I will conclude by sharing plans for my independent lab, launching May 2025 at Northwestern University Feinberg School of Medicine, where we will work to decipher the “spatial code” of mRNA within cells. In particular, we will uncover the molecular features of mRNAs that drive localization to condensates in the nucleus and cytoplasm. Using a combination of live-cell imaging and bottom-up reconstitution, we will examine the functional impacts of condensate localization on mRNA nuclear export, long-distance transport, and translation. Through our work, we aim to acquire new insights into the molecular origins of human diseases and identify new opportunities for therapy.

Host:  Xingcheng Lin