BMOL Seminar Series: Dr. Aleksandar Necakov

Presenter Information

Speaker: Dr. Aleksandar Necakov, Assistant Professor of Biological Sciences at Brock University

Short Description of Research: The central theme of our research program is the Notch signaling pathway. The Notch pathway is a cell-to-cell communication system used by multi-cellular animals to ensure the correct cell types form at a precise time and location in the body. In recent years, our understanding of the mechanisms that govern Notch signaling has grown significantly and provided insights into the cellular and genetic requirements for Notch. In particular, endocytic trafficking, the process by which cells internalize, sort, integrate, process, and secrete intercellular signaling components, has emerged as a critical regulator of Notch signaling. However, the complex, interconnected architecture of cellular signaling networks has posed formidable challenges to disentangling how cells process and integrate information. To circumvent these challenges, we apply a combination of genetic engineering, high resolution live imaging, and Optogenetics to precisely visualize and control components of the Notch pathway and the endocytic trafficking machinery with light.

Seminar Details

Host: Dr. Allan Albig, Biological Sciences

Title: Self-assembly of Notch1 transcriptional condensates facilitates target gene expression

Abstract: The Notch receptor is a titratable, context-specific counter of intercellular contacts that translates productive interactions with ligands on neighbouring cells into corresponding changes in gene expression via the nuclear localization of the Notch intracellular Domain (NICD). Using a combination of immunohistochemistry, RNA in situ, Optogenetics and super-resolution live imaging of transcription in human cells, we show that the N1ICD activates gene expression through spontaneous self-assembly into transcriptional condensates driven by an Intrinsically Disordered Region (IDR) of the N1ICD. We show that the N1ICD undergoes Phase Separation Coupled Percolation (PSCP) into transcriptional condensates, which recruit, enrich, and encapsulate a broad set of core transcriptional proteins, thereby promoting super enhancer-looping and concomitant activation of MYC oncogene expression. We introduce a model of Notch1 activity in which discrete changes in nuclear N1ICD abundance are translated into precise increases in target gene expression through the assembly of dynamic, transcriptional condensates that catalyze gene expression by enriching essential transcriptional machineries at target genomic loci.

Publication Related to Talk: Notch1 forms nuclear transcriptional condensates that drive target gene expression