Prehoda Lab
Affiliations: Molecular Biology · Chemistry · Biology
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Recent News
Sept 23, 2009: Jana's paper on allosteric control of Discs Large is published
Sept 17, 2009: Chris' paper on inducing polarity in unpolarized cells to control the spindle is published
August 27, 2009: Rhonda Newman will be joining the stem cell division of Life Technologies. Congratulations Rhonda - we'll miss you!
June 19, 2009: Nick Smith will be speaking about his work on ultrasensitive regulation at this summer's Protein Society meeting.
June 9, 2009: Welcome to new graduate students Mike Drummond and Jon Mauser and summer student Lizzy Hubin.
May 8, 2009: Derek Ricketson has been awarded his PhD. Congratulations Derek!
Research in Cellular Signal Transduction
What are the molecular events that give rise to complex cellular behaviors? This fundamental question drives much of the research we do. Cells have the remarkable ability to respond to changes in their environments. For example, neutrophils "see" foreign cells such as bacteria and rapidly remodel their cytoskeleton to move towards and engulf them. During development, certain cells receive inputs from their surroundings to divide in such a way to generate daughter cells with distinct fates (i.e. differentiate). What occurs subsequent to the recognition events on the surface of these cells that give rise to the complex behaviors that they exhibit?
Deciphering the mechanisms of protein interaction based regulation
Dynamic protein interactions underlie much of the signal transduction networks that regulate biological processes. How are protein complexes dynamically assembled and disassembled to spatially and temporally control cellular function? Large, multi-domain signaling proteins have the potential to bind many ligands, and the net "input-output" response profiles that they generate often include complex characteristics such as thresholding and ultrasensitivity. What are the molecular origins of these complex phenomena, given that they are built upon simple binary interactions?
Mechanism of neuroblast asymmetric cell division
To answer this question, we study the proteins responsible for asymmetric cell division, a process used by certain stem cells to generate cellular diversity. During asymmetric cell division, cell fate determinants become polarized along the cell cortex and the cleavage furrow forms in such a way that the determinants become segregated into distinct daughter cells. This molecular asymmetry leads to cell fate asymmetry. There are two fundamental aspects of asymmetric cell division. The first is the polarization of the fate determinants along the cell cortex, a process known as cortical polarization. Second, the cleavage furrow must properly bisect the polarized fate determinants and the furrow position is largely determined by the orientation of the mitotic spindle apparatus. Thus, proper asymmetric cell division requires cortical polarization of fate determinants and alignment of the mitotic spindle with the axis of cortical polarity. An example of an asymmetrically dividing cell is the Drosophila neuroblast which generates the central nervous system. In the movie above, a dividing embryonic neuroblast is being imaged with a Green Fluorescent Protein fusion to the myosin II regulatory light chain. We are using this system to investigate the molecular mechanisms of polarity and mitotic spindle positioning.