Follow the Leader: Forecasting Collective Cancer Dynamics (ASUF 30007809)

Project: Research project

Project Details

Description

Follow the Leader: Forecasting Collective Cancer Dynamics (ASUF 30007809) Follow the Leader: Forecasting collective cancer dynamics Background: Cancer invasion by an organoid, a group of cells, is directed by leaders. Leaders are phenotypically distinct cells that degrade the extracellular matrix (ECM) at the periphery of the organoid, providing microtracks that other cells may follow. The leaders role is transient, and little is known about how tumor organoids elect a leader or establish and update the hierarchy amongst followers. Overarching Goal: Here we will screen novel metabolic and rheological markers for all cells within the organoid (Milestone 1); use a combination of theory and experiments to predict hierarchical roles and changes (Milestone 2). Milestone 1 Screen for rheological markers and build a statistical framework that predicts cell roles in the hierarchy on the basis of those markers. Tasks 1) We will measure cytosolic water dynamics within cells of an organoid using the solvato-chromic properties of ACDAN and LAURDAN (and NADH if time allows). 2) We will identify rheological marker from imaging. Repeat the experiments as a function of the organoid size. 3) Use the data to (soft) cluster cells according to types and determine at what critical size (if any) an organoid begins exhibiting cells of distinct types. Milestone 2 To predict who is elected as leader by artificially rebooting the hierarchy. Tasks 1) To stress the hierarchy, laser ablate the leader cell or introduce hypoxia and see if this induces a hierarchical remodeling (if time allows, poison the extracellular matrix in which organoid is located in order to introduce a penalty to the leader that consumes the matrix to create a path for followers). 2) On the basis of the markers obtained from milestone 1, predict the remodeling that will occur by building a posterior probability map of the role that a cell may adopt.
StatusFinished
Effective start/end date9/13/174/1/19

Funding

  • Gordon and Betty Moore Foundation: $56,250.00

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