Current Research Interests:

I have 2 main research interests: Super Resolution (SR) Microscopy and Nonlinear (NL) Microscopy

Super-Resolution Microscopy by Single Molecule Localization

Single Molecule Localization Microscopy (SMLM) is a powerful method to achieve nanometer resolution in biological samples using a simple optical microscope. It relies on inducing stochastic blinking in the fluorophores used to label the structure of interest by using chemical buffers that affect their photophysics. Our aim is to develop methods to improve super-resolved tissue imaging by focusing on different technical developments:

Multicolor Imaging

Although there has been steady progress in multicolor imaging since the inception of the method, it is still not straightforward to perform high quality multicolor 3D imaging. Our aim is to focus on the chemical buffers used to induce the stochastic blinking in order to achieve improve multicolor imaging. For recent progress on the topic, see [1,2].

Tissue Imaging

Most single molecule imaging is done on cells grown on glass to be in perfect imaging conditions and maximize the signal-to noise ratio. We want to move to tissue imaging by combining work on imaging buffers and dyes used, optical developments such as light-sheet illumination, and computational post-acquisition methods.

Archaea Imaging

In collaboration with Roxane Lestini @ LOB, who previously used live-SIM microscopy to study DNA replication and repair in Haloferax Volcanii we are using STORM microscopy to further our understanding of the DNA replication process to the nanoscale. In particular, we are interested in the relationship between the spatial distributions of different proteins involved in the replication process, and newly synthesized DNA. See [5]

Coherent Nonlinear Microscopy

Coherent nonlinear microscopy techniques such as Second Harmonic Generation (SHG) or Third-Harmonic Generation (THG) provide 3D images of unstained biological tissues (such as skin, cornea, brain tissues or Zebrafish Embryo to name a few tissues studied at LOB), and can be used on their own or to provide context to multiphoton excited fluorescence images of specific markers of interest. In particular, our work focuses on quantitative modelling of THG microscopy, which has particularly complex contrast mechanisms, using numerical methods such as the Finite Difference Time-domain (FDTD) method. For recent progress on the topic, see [6,7]

Other Interrests

Expansion Microscopy

Kate is currently trying to adapt the U-EXM protocol for Haloferax Volcanii.

Extended Depth-of-Field Imaging

I am interested in different approaches to control the depth-of-field, both on the illumination side and detection side.

References:

Super-resolution

1 - An Optimized Buffer for Repeatable Multicolor STORM Vaky Abdelsayed, Hadjer Boukhatem, & Nicolas Olivier (2022). Now also peer-reviewed (paywalled)

2 - Evaluation of Slowfade Diamond as a buffer for STORM microscopy Hadjer Boukhatem, Beatrice Durel, Manon Raimbault, Audrey Laurent, and Nicolas Olivier (2023)

3 - Resolution doubling in 3D-STORM imaging through improved buffers Nicolas Olivier, Debora Keller, Pierre Gönczy, & Suliana Manley (2013)

4 - Simple buffers for 3D STORM microscopy Nicolas Olivier, Debora Keller, Vinoth S. Rajan, Pierre Gönczy, & Suliana Manley (2013)

5 - BrdU Incorporation and Labeling of Nascent DNA to Investigate Archaeal Replication Using Super-Resolution Imaging Roxane Lestini,  Yoann Collien,  Debora Olivier,  Nicolas Olivier, & Hannu Myllykallio (2022). Now also peer-reviewed (paywalled)

Coherent Nonlinear Microscopy

6 - Modeling nonlinear microscopy near index-mismatched interfaces Josephine Morizet, Giovanni Sartorello, Nicolas Dray, Chiara Stringari, Emmanuel Beaurepaire, & Nicolas Olivier (2021)

7 -Third harmonic imaging contrast from tubular structures in the presence of index discontinuity Josephine Morizet, Nicolas Olivier, Pierre Mahou, Arthur Boutillon, Chiara Stringari, & Emmanuel Beaurepaire (2023)