Research:
We use budding yeast to look for general principles that underlie the function and evolution of cells, as revealed by studying the transmission of genetic information during cell division, mating, and how cells evolve in response to selective pressure. We try to make quantitative measurements that discriminate amongst different classes of models and members of the lab come from both biology and physics backgrounds. In general, we are more interested in using genetic and physiological perturbations to understand the “rules of the game” than understand the chemical functions of individual proteins. How does mitosis segregate a cell's chromosomes into two identical sets before cell division? This question has fascinated biologists for over a century and is directly relevant to cancer and other important medical problems. We study two aspects of chromosome behavior: how chromosomes attach to the chromosome segregation machinery (the spindle) in mitosis and meiosis, and the spindle checkpoint, the control circuit that cells use to make sure that their chromosomes are properly lined up on the mitotic spindle before initiating chromosome segregation. Budding yeast has two mating types and can exist stably as both haploids and diploids. We use microfluidics, video microscopy, and genetic manipulation to ask how cells pick a single axis of polarization when they are exposed to mating pheromones, how this axis is aligned to pheromone gradients, and how pairs of cells efficiently court and then fuse with each other in dense mixtures of mating cells. Our results suggest that cells use the cytoskeleton to integrate signaling from all parts of the cell surface in way that guarantees a single axis of polarity. How does selective pressure induce the evolution of new traits and how predictable is the outcome of such experiments? We study both general and specific questions. The general questions include attempting to use theory and experiment to determine how the rate of evolution depends on population sizes and the beneficial mutation rate, evolving altered mating preferences (a first step towards speciation), investigating the advantages of mutators, evolving cooperation, and determining the distribution of beneficial and deleterious mutations. The more specific projects use the mating pathway and attempt to create connections to other signaling pathways and turn the pathway from a rapidly reversible and graded response into a stable switch that can be thrown by a single exposure to mating pheromone.
Selected Publications: Reviews, Commentary Hartwell, L.H., Hopfield, J.J., Leibler, S. and Murray, A.W. 1999. From molecular to modular cell biology. Nature 402, C47-52. Murray, A.W. 2004. Recycling the Cell Cycle: Cyclins Revisited. Cell 116, 221-234. Ingolia, N.T. and Murray, A.W. 2004. The Ups and Downs of Modeling the Cell Cycle. Curr. Biol. 14, R771-R777. Articles Leu, J-Y. and Murray, A.W. 2006. Experimental Evolution of Mating Discrimination in Budding Yeast. Curr. Biol. 16, 280-286. Palframan, W.J., Meehl, J.B., Jasperson, S.L., Winey, M., and Murray, A.W. 2006. Anaphase Inactiviation of the Spindle Checkpoint. Science, 313 (5787):680-4. Thompson, D.A., Desai, M.M., and Murray, A.W. 2006. Ploidy Controls the Success of Mutators and Nature of Mutations During Budding Yeast Evolution. Current Biology, 16, 1581-1590. Desai, M.M., Fisher, D.S., and Murray, A.W. 2007 The Speed of Evolution and Maintenance of Variation in Asexual Populations. Current Biology 17, 385-94. Ingolia, N. and Murray, A.W. 2007. Positive Feedback Loops as a Flexible Biological Module. Current Biology, 17, 668-77. Lacefield Shimoda, S. and Murray, A.W. 2007. The spindle checkpoint rescues the meiotic segregation of chromosomes whose crossovers are far from the centromere. Nature Cell Biol. 39, 1273-7. Indjeian, V. and Murray, A.W. 2007. Budding Yeast Mitotic Chromosomes Have an Intrinsic Bias to Bi-Orient on the Spindle. Current Biology, 17, 1837-46. Lang, G. I. and Murray, A. W. 2008. Estimating the per-base-pair mutation rate in the yeast, Saccharomyces cerevisiae. Genetics, 178, 67-82. Lacefield, S., Lau, D.T.C., and Murray, A.W. Construction of a synthetic kinetochore in budding yeast. Nature Cell Biology, in press. |
