Cissé Laboratory

he Cissé laboratory uses physical techniques to visualize weak and transient biological interactions, to study emergent phenomena in live cells with single molecule sensitivity.

In physics, problems involving a system of many interacting particles can be quite intricate to solve from first principles. Even if affinity is very low between individual components, the system can exhibit cooperative functions where the collective is more than the sum of the individuals. Such emergent phenomena underlie complex systems from the macroscopic scale, down to how our genome self-regulates in living cells. However, apprehending emergent phenomena in a laboratory setting is a fantastic challenge. We capture and study these collective behaviors directly in living cells using quantitative approaches based on fluorescence, so called super-resolution, techniques that enable high spatial localization (tens of nanometers; well below the optical diffraction limit) and high temporal resolution (tens of milliseconds).

In Biology, weak and transient interactions are involved in many processes in the cell, but difficult to detect and study by conventional techniques. These are ubiquitous, non-constitutive interactions suspected to play regulatory roles in the molecular mechanisms behind cell proliferation, protein folding, non-coding RNA sense-antisense target recognition and gene expression regulation. These interactions are highly dynamic and usually involve non-covalent bonds with strengths on the order of the thermal energy. They include biomolecular complexes with a dissociation constant (KD) too high to purify intact or reconstitute in vitro, and also those requiring high copy number of proteins which present a detection problem for in vivo fluorescence microscopy. As such, weak and transient interactions have remained relatively under-explored in the biological sciences. The lab aims to overcome these technical limitations by leveraging novel biophysical approaches based on single-molecule imaging.

The approach is to develop and use highly sensitive experimental techniques capable of detecting and quantifying in a meaningful manner weak and transient biomolecular interactions. We have developed biophysical tools to measure weak and transient interactions both among isolated biomolecules (in vitro), and directly inside individual living cells with single-molecule sensitivity. Currently, we set out to understand what roles weak and transient interactions play in regulating genomic processes and nuclear organization at the single-cell level.