Wallace F. Marshall
Department of Biochemistry & Biophysics
University of California, San Francisco
Genentech Hall N372F
600 16th St.
San Francisco, CA 94143
2005 Searle Scholar
How Cells Count and Measure
Modern cell biology has made great strides in understanding cell structure and function. As with any engineering problem, however, there is a third important aspect that needs to be understood besides structure and function, and that is assembly. How are the complex three dimensional structures found within the cell specified by a one-dimensional genome? My long-term research goal is to understand how the size, number, and position of every organelle in the cell is determined by the genome, using a combination of genetic, imaging, and mathematical approaches.
So far I have concentrated on two model systems: centriole duplication as a system to study organelle inheritance, and flagellar length control as a system to study organelle size regulation. My work takes advantage of the unicellular green alga Chlamydomonas (also known as "green yeast"), which has many of the same advantages as yeast for genetic experiments, and whose genome has recently been sequenced, but which has centrioles and flagella identical to animal cells.
The major research focus of my lab will be to understand the function and duplication of centrioles, using Chlamydomonas as a genetic model system. This work is motivated by the fact that centrioles are thought to be critical for proper cell division and chromosome segregation, and abnormalities of centriole number are a common feature of cancer cells.
Aim 1. Identify genes required for centriole duplication and number control.
Aim 2. Identify the protein components of the centriole.
Aim 3. Determine centriole function in chromosome segregation and cell division.
The other major goal of my lab will be to understand how organelle size it determined. Flagella are an ideal system for asking this question because their size is easily measured. I have previously shown that a simple mechanism for flagellar length control based on the inherent length-dependence of intraflagellar transport can account for most prior experimental data on length control. I am currently testing several novel predictions of this model, for example the prediction that flagellar length should vary as a function of the number of flagella present in a cell. In the near future my future work on flagellar length control will center around understanding mechanistic basis of long-flagella (lf) and short flagella (shf) mutants that have abnormal flagellar length. Ultimately I plan to test whether a similar type of mechanism can account for size control in other organelles.
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