EPFL BioEngineering Talks

Weekly BioEngineering Talks (Lunch Provided)

INVITED SPEAKER:

Advancing Multidimensional Single-Molecule localization microscopy: development and applications in nuclear organization
Dr. Bassam Hajj, Institut Curie, Paris
Host: Prof. Aleksandra Radenovic

Abstract:
Single-molecule localization microscopy (SMLM) has revolutionized our understanding of biological processes by providing access to spatial scales beyond the diffraction limit of conventional optical microscopy. In the study of the cell nucleus, SMLM has offered unique insights into its organization and function at the nanoscale. Nuclear architecture is structured across multiple spatial scales in three dimensions and is highly dynamic. Understanding the mechanisms that govern nuclear organization therefore requires imaging approaches capable of capturing molecular dynamics across a broad range of spatial and temporal scales and in diverse biological contexts. Although SMLM can routinely achieve spatial resolutions in the tens-of-nanometers range, many biologically relevant structures and processes remain beyond its reach. For example, resolving the precise organization of DNA at the molecular scale remains challenging, as it would require a substantial improvement in spatial resolution over conventional SMLM, while also addressing the high density and degree of molecular compaction within the nucleus. 
Over the years, we have developed complementary strategies to address these challenges by introducing additional dimensions and observables into SMLM measurements. In this presentation, I will first discuss our approaches to three-dimensional single-molecule imaging, including multifocus microscopy and volumetric light-sheet excitation, which enable fast and sensitive imaging over extended volumes and in complex biological samples such as cell colonies. While these approaches provide access to the three-dimensional and temporal dimensions required to investigate nuclear organization, spatial resolution alone is not always sufficient to distinguish molecular arrangements. We have therefore extended SMLM further by implementing polarization-resolved multifocus microscopy (PolMFM), which combines three-dimensional localization with information on molecular orientation.
I will illustrate how these multidimensional approaches can provide new insights into nuclear organization, with examples spanning different biological systems. In particular, I will present evidence for a long-range, crystal-like organization of DNA within the nuclei of mature sperm cells from crickets, demonstrating how multidimensional imaging can reveal structural features that remain inaccessible to conventional localization microscopy.
Finally, I will discuss the challenges and opportunities associated with visualizing, analyzing, and interactively exploring the multidimensional datasets generated by these approaches. Together, these developments illustrate how extending SMLM beyond conventional two-dimensional localization can provide new ways to interrogate the organization and dynamics of biological systems at the nanoscale.


Bio:
Bassam Hajj is a physicist and CNRS researcher at Institut Curie in Paris, where he is a member of the Physics of Cells and Cancer unit and co-leads the “Light-based Observation and Control of Cellular Organization” team. His research focuses on the development of advanced optical microscopy techniques, particularly single-molecule localization microscopy, 3D imaging, and multidimensional approaches for studying cellular organization at the nanoscale.
After completing his PhD at École Normale Supérieure de Cachan on electro-optical microscopy, Bassam joined Janelia Research Campus as a postdoctoral researcher, where he worked on multifocus microscopy for fast and sensitive single-molecule imaging. He subsequently returned to Institut Curie and joined the CNRS as a permanent researcher in 2016.
His current research combines innovative microscopy, quantitative image analysis, and data visualization to investigate molecular organization and dynamics, with a particular focus on nuclear organization.

STUDENT SPEAKER:

Transcription Factor Dose in Stem Cell Reprogramming: Insights from Single-Cell Multi-Omics
Angelika Gebhart, Deplancke Lab


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