LabEx Cell(n)Scale
Search

Scientific objectives

LabEx CelTisPhyBio
10/16/2019
Partager
Since 2012, the LabEx CelTisPhyBio has been promoting research at the interface betweeen physics, chemistry and cell biology along original research axes with the ultimate aim of developing novel innovative technologies and potential therapeutics. Its scientific strategy is structured along three axes, based on a multiscale approach.
actin sunflower
  • Axis 1. Supramolecular assembly & subcellular structures

supramolecular assemblies

The large variety of cellular functions emerge as a result of the proper distribution and synchronization in time and space of a multitude of components. This "orchestration" relies for a large part on the formation of local assemblies of molecules that form clusters at the cell membranes, in the cytoplasm or in the nucleus, leading to spatiotemporal heterogeneities that play a crucial role in controlling the distribution, amplitude and dynamics of exchanges between cellular organelles, or in organizing and remodeling cytoskeleton components. Identifying these protein assemblies and deciphering the biochemical and physical origins of these local heterogeneities is thus particularly important for understanding cellular functions such as adhesion, signaling, trafficking, gene expression or DNA replication. Moreover, at a more coarse-grained level, the cell is made of many different types of internal organelles with specific biochemical "identities" that are precisely distributed in space. How sub-cellular heterogeneity emerges from intracellular exchanges and biochemical reactions and from cytoskeleton organization is still an open question. Teams of the LabEx Cell(n)Scale will tackle these challenging issues, leveraging their cross-disciplinary experience and a wide arsenal of techniques ranging from cryo-EM and super-resolution to optogenetics and micromanipulation, the development of reconstituted systems and theoretical modeling.

 

  • Axis 2. Regulation of cellular functions

regulation of cellular functions

The cellular scale has a peculiar role in biology. Indeed, it is the smallest scale at which autonomous biological systems are found. In addition, in metazoans, cells are the building blocks for tissues and organs. Molecular and cellular processes such as signaling, membrane trafficking or cytoskeletal dynamics cannot be studied in separation but should be considered as integrated events at the cell scale. Biochemical and biophysical cues from the extracellular environment (from neighbor cells, the extracellular matrix…) or cell autonomous signals influence cells’ genomic, transcriptomic and proteomic status and impinge on cell fate and functions. Thus, it is essential to understand how coordination of elementary cell mechanisms and regulation by cell and environmental cues contributes to homeostasis and to fundamental cell functions such as cell migration or cell division. Reciprocally, cells’ biomechanical and biophysical properties influence the organization and function of the tissues they belong to and modify their environment. Also, of tremendous importance, dysregulation of biophysical and mechanical properties of cells and their environment can contribute to disease initiation and progression such as in life-threatening cancers. Thus, it is of great opportunity for biologists and physicists within this LabEx to pursue the understanding of how cellular functions emerge as a coordination of molecular and supramolecular processes and how cells develop an internal representation of their environment to adapt and interact with it. The challenge for this interdisciplinary action focused on cellular functions is to develop new tools and approaches to integrate the complex interplay between the numerous chemical and physical processes that compose the cell at different scales. From the biological point of view, we still lack an understanding of how the diverse subcellular activities, such as gene regulation, protein trafficking, signaling, are coordinated in space and time to achieve the cellular functions. We also have little knowledge about how a combination of diverse environmental cues is mapped into specific cellular states. From the physical perspective, we investigate how global cellular processes are self-organizing from a complex mixture of elementary molecular events. We address these challenges around three main directions: cell migration, cell division and cell plasticity.

 

  • Axis 3. Multicellular assemblies

multicellular assemblies

Intercellular communication is a key property of organized living systems. It leads to transfer of information and coordinated regulation of key biological functions within cell populations, and the development of normal tissues or tumors is characterized by both biochemical and mechanical patterning. Here, we focus on describing in a quantitative manner how the physical cues of tissues impact their normal and tumorigenic states - for instance in the context of collective cell migration, tissue proliferation and morphogenesis, or cell interactions with the microenvironment and cell competition. To do so, we use novel technological developments and interdisciplinary approaches that involve developmental and cell biology, as well as experimental and theoretical physics. Our research projects rely on different systems, from whole organisms to organoids or “organs on chips”, as well as on theoretical modelling, whether based on continuous approaches or numerical simulations.

    LabEx_Logo_bottom_white

    The onset of the project, 2012 - 2019

    Research at the interface between physics and cell biology has been a focus at Institut Curie over the past decades. It is on this basis that the LabEx CelTisPhyBio was founded in 2012. It has enabled researchers at Institut Curie, ESPCI and more broadly at PSL to develop a quantitative cell biology approach based on the physical properties of cells, not only at the single cell level but also at the level of the collective behavior of cells within a tissue. The long-term aim of these studies has been to apply the results to cancer and tumor growth research and to the development of new therapeutic approaches.

    The project renewal, 2020 - 2024

    Following successful 2018 evaluation of the LabEx CelTisPhyBio by the ANR, the LabEx has been renewed from 2020 to 2024, and renamed Cell(n)Scale. The LabEx scientific strategy is built in continuity with the initial 2012-2019 project. Two dimensions will however be strengthened: the interface with computational biology and mathematical modelling-to go a step further in the comprehension of biological processes, and chemical biology approaches-to enhance the synthesis of small molecules key for the development of several research projects.