A Very Basic Introduction
Why S. cerevisiae?
S. cerevisiae is a choice organism to study. Most importantly, budding yeast exhibit many of the fundamental properties of cells in other eukaryotes such as human cells. Second, due a number of powerful techniques and resources, these fundamental properties can be dissected rapidly and exactingly in S. cerevisiae. For example, the life cycle of budding yeast is simple yet includes diverse features such as meiosis and cell-cell signalling during mating.
All cells in our body contain the same genetic information, yet they exhibit vastly different features. During the development of the human embryo, cells make specific decisions to adopt different fates. Often, these decisions are made by sensing signals within the cells and signals from the environment. Once processed, these signals frequently result in changes in gene expression and cells morphology. So too, yeast cells exhibit different fates and make very precise and intelligent decisions based on sensing a number of internal and external signals.
•Internal Spatial Information
Our lab studies internal spatial signals that affect both gene expression and cell morphology. In the first case, a spatial asymmetry permits only the mother yeast cell to transcribe the HO endonuclease gene. In the second case, a inherited landmark at the cell periphery positions the site of emergence of the future daughter cell. Both these signals are derived from lineage determined events occuring during budding yeasts asymmetric division cycle. Determining the exact origin of these signals and their mechanism of controlling future events is one of our goals.
•External Spatial Information
We also are interested in how yeast respond to external signals from the environment. In particular, yeast cells polarize their cytoskeleton in response to phermones from yeast of the opposite mating type -- a process called shmooing. While it is clear the phermone activates a receptor at the cell surface and thus stimulates a cascade of signalling protein kinases, until recently little is known about how this signal cascade spatially orients the cytoskeleton. We wish to determine how these signalling events cause a dramatic and precise alteration in cell morphology.
These events lead to the mating of two cells of the opposite mating type that are polarized toward each other. We hope to unravel the subsequent events that may involve additional signalling events, cell wall degradation, and membrane fusion which culminate in cell and nuclear fusion.
•Cell Cycle Control
The generation and usage of spatial information is tightly coupled with temporal events in the yeast cell cycle. For example, budding only occurs at the START transition, point of commitment to S phase entry. The HO endonuclease gene also is only activated at START. The URS2, a precisely defined region of the HO promoter is responsible for restricting its expression to this phase of the cell cycle. We are identifying potential cell cycle specific repressors of HO transcription that are required for regulating this event. We would also like to understand what events generate the initial decision to progress to START. Assessment of cell size and nutrient levels may precisely modulate the levels of cyclins, essential activators of CDC28, the central kinase controlling START.
The events of the cell cycle can also be dramatically altered in diploids to include a second divisional event which leads to the generation of haploids. This modification, which is special to meiosis, requires a special set of genes. We are attempting to identify and understand all the specialized genes required for the meiotic cell cycle.