Research

The cells you see here have something in common:
...They are all polarized.
Cell polarity - when two sides of a cell are molecularly distinct - is a basic property of eukaryotic cells. Nearly every cell in your body has to polarize in order to function normally.  That includes epithelial cells, neurons, migrating cells, immune cells and dividing stem cells. When polarity is disrupted, disease often results. 
 
Cell polarity is a fascinatingly complex behavior

 aPKC

PAR-6

PAR-3

CDC-42 

PAR-1/MARK

PAR-4/Lkb1

Lgl

Dlg

Scribble

 

Conceptually, polarity arises because two groups of proteins localize to opposite ends of a cell and mutually antagonize each others' binding. But what are the biochemical interactions that lead to mutual antagonism? What determines the direction of the polarity axis and the timing of polarity establishment? How do cells coordinate their polarization with neighboring cells or other aspects of their environment? These are the questions we lie awake at night pondering. 
A unique, interdisciplinary approach
We study cell polarity using a multidisciplinary approach. 
  • We do most of our work with a carefully-chosen in vivo model system: the C. elegans zygote, which polarizes in a simple and stereotypical manner in response to known spatial and temporal cues.
  • We use high-resolution, quantitative fluorescence microscopy of living zygotes to study protein dynamics during cell polarization. To avoid expression-level artifacts, we work almost exclusively with proteins tagged at their endogenous loci.
  • To gain dynamic information about protein-protein interactions, we use a single-cell biochemistry method that Dan developed during his postdoc. Briefly, we lyse staged zygotes in nanoliter volumes and quantitatively measure protein-protein interactions using single-molecule pull-down. 
  • We test specific hypotheses by engineering targeted mutations into endogenous genes.