Description of the PhD project
Super-resolution optical microscopy, awarded by the Nobel Prize 2014, represents a true revolution in biology. Their ultimate sensitivities, allowing the tracking of unique molecules, as well as their nanometric resolution, unveil, for the first time, the organization and intracellular mechanisms at the molecular level.
Diffraction has long been considered as a fundamental limitation to the spatial resolution of optical imaging systems. Numerous biological applications were thus excluded by the impossibility of imaging molecular structures smaller than 200 nm. Recent developments in super-localization microscopy techniques (dSTORM / PALM) make it possible to achieve a lateral positioning accuracy of about 10 nm, by acquiring at different times the emission of fluorophores which lie in the response function of the microscope. In our group at Langevin Institute, we are developing innovative strategies to improve both lateral and axial resolution to optimize the acquisition of biological information at the nanoscale (Nature Photonics 2015, Nature Communications 2015, ACS Nano 2017). We also focus on the ability to retrieve additional information at the single molecular level like the orientation or the chemical local environment.
Accessing the local environment at the scale of an individual molecule within a cell would represent a true breakthrough in biology by allowing one to go beyond statistical averaged measurements. Despite the efforts of many research teams in this field, this remains very difficult, if not impossible. This project will use an innovative concept to retrieve information at the single molecule level without compromising the localization precision. It provides a direct access to this information through the acquisition of the molecule fluorescence lifetime. Being compatible with standard super-resolution microscopy, without degrading their performance, this concept takes advantage of the whole set of photons emitted by the molecule to extract information. Inter-molecular variability will become a new and extraordinary source of information for the understanding of cellular mechanisms. This interdisciplinary project involves the active collaboration of several groups.
The first part of this project consists in implementing this new microscopy. After a step of validation of the performances of the device on calibrated samples, the observations of samples of biological interest will be performed in collaboration.
Description of the research Unit/subunit
UMR7587 Langevin Institute
The candidate will be hosted at the Langevin Institute.
The Langevin Institute is a research unit affiliated with ESPCI Paris and CNRS. The researches conducted at the Institute aim at developing at the best world-level the physics of waves bringing together high level fundamental research, applied research, and company start ups in a thoroughly cross-disciplinary way.
This project is directly connected to several key enabling technologies (photonics, nanotechnology, biotechnology with biochemistry and molecular labelling. The outcome of the project is of direct interest for this industrial partner Abbelight which cofund this PhD program. Abbelight is an innovative company in super-resolution microscopy that is interested in getting licensed for this patented technology.
This project has a very strong interdisciplinary component and involves optics, biochemistry, image processing and biology. The success of this project is based on the active collaborations with several groups, experts in the different fields.
This interdisciplinary project involves several international collaborations in particular strong exchanges with the Tjian & Darzacq Group at Berkeley. Probable visits and exchanges with this group (to perform experiments) will take place during the project.