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Cell Atlas

intracellular architecture

Part of our Cell Atlas Initiative, the Leonetti group is interested in mapping the internal architecture of human cells. While the human genome sequence provides us with the list of molecular machines (the proteins) that make up our cells, we are still far from understanding how all of these molecular components come together to generate living systems. By combining recent advances in gene editing, fluorescence microscopy and proteomics, Leonetti and his team aim to understand how cells are internally organized in space and time. Their shared objective is to unravel the changes at play when diseases strike.




We are interested in describing and understanding how human cells are built as ecosystems of molecular machines. We are motivated not only by how this will help characterize fundamental mechanisms in physiology and diseases, but also by the process of “reverse engineering” a cell – understanding the details of how it is built to be able to predictably tune its properties and behavior.

To start, we are asking: Where are all the proteins in a cell localized, and how do they interact with each other? For this, we develop and deploy a variety of technologies to “illuminate” proteins and manipulate them:

  • We specialize in the development of scalable CRISPR gene editing methods to create genome-scale libraries of fluorescently labeled cell lines.
  • We build software and hardware automation to streamline the design, execution, and analysis of our experiments.
  • We use high-throughput live cell fluorescence microscopy to map protein localization in space and time.
  • We use proteomics mass-spectrometry to profile protein-protein interactions and delineate functional networks.

Our goal is to build open datasets, software, and protocols for the entire community to use and explore.

More about our project in this recent talk




You can view our publications here.