Quantitative modeling of the PAR polarity network


goehring2

Supervising PI

Nathan Goehring (website)

Project Description

Background

PAR proteins were identified in C. elegans over 20 years ago. However, it remains unclear how the mobilities of and interactions between individual PAR components combine to generate patterns at the cellular scale, let alone how they provide a system that is robust and adaptable to divergent cell types. Understanding these emergent behaviors requires mathematical modeling of the PAR network informed by experimentally determined parameters governing protein mobility and interaction affinities. In this project we will take a systems-level approach to defining the mobilities of, and interactions between PAR proteins and use this data to guide implementation of new models for self-organisation of PAR polarity.

Objectives

  • Define dynamic behavior of PAR proteins in vivo / in vitro.
  • Definite potential interactions between PAR proteins in vitro / ex vivo.
  • Generate comprehensive model for PAR self-organisation.

Methodology

Genome modification, quantitative live cell imaging, single-molecule imaging, biochemistry / in vitro assays, mathematical modeling.

Collaborators

Key publications

(1–3)

  1. Goehring NW. PAR polarity: from complexity to design principles. Exp Cell Res. 2014 Nov 1;328(2):258–66.
  2. Goehring NW, Trong PK, Bois JS, Chowdhury D, Nicola EM, Hyman AA, et al. Polarization of PAR proteins by advective triggering of a pattern-forming system. Science. 2011 Nov 25;334(6059):1137–41.
  3. Goehring NW, Hoege C, Grill SW, Hyman AA. PAR proteins diffuse freely across the anterior-posterior boundary in polarized C. elegans embryos. J Cell Biol. 2011 May 2;193(3):583–94.