Interview Seminars
Assistant Professor in Plant Cell Biology Faculty Position
G. VENUGOPALA REDDY
California Institute of Technology
Location: Science Library, Rm 240
Day/Date: Tuesday, February 28, 2006
Time: 10:10am
Title:
"Imaging regulatory interactions in stem-cell homeostasis:
From genetic epistasis to biological function"
Abstract:
Stem-cell homeostasis is a dynamic process that results from active orchestration of the spatio-temporal patterns of gene expression, and of cellular behavior, by cell-cell communication. The challenge is not only to identify molecular components that mediate stem-cell homeostasis, but also to understand how cells interpret a combination of local cues and global signals to adjust their division behavior and gene expression patterns, thereby maintaining a functional stem-cell niche. I utilize shoot apical meristems (SAM) of Arabidopsis thaliana as a model system to study stem-cell homeostasis. SAMs of flowering plants have a remarkable ability to maintain a stable pool of stem-cells despite constant diversion of cells to differentiation pathways. Conventional genetic analysis has yielded a molecular framework that mediates stem-cell homeostasis. However, analysis based on terminal phenotypes of mutants is inadequate to define the function of individual genes in the network of interacting cells. Resolving the function of individual genes in an interacting network would involve creating transient perturbations in gene activities by turning them off/on in a living, wild-type SAM and following in real time the changes in the organization of the SAM. I have developed methods to transiently alter gene activities in wild type SAMs and to record real-time changes in cell identities and cell behavior. A brief summary of novel mechanistic insights into the process of stem-cell maintenance, mediated by CLAVATA -WUSCHEL regulatory network will be presented. I will also discuss a conceptual framework for future experiments to address questions such as; how do global cues provided by plant hormones, light and temperature interact with local cell-cell communication machinery to maintain a functional stem-cell niche? My talk will also highlight the importance of transient intervention and in-vivo imaging in conducting hypothesis-driven research, thereby deciphering cellular and molecular networks that function in stem cell homeostasis.
KIMBERLY GALLAGHER
Duke University, Durham, North Carolina
Location: Science Library, Rm 240
Day/Date: Monday, March 6, 2006
Time: 12:10am
Title:
"Examination of the Mechanism of
SHORT-ROOT
Cell-to-cell Signaling"
Abstract:
In the Arabidopsis root the formation and differentiation of the ground tissue requires the activity of two related transcriptional regulators, of stem cells in the root apex through the activation of SCR. Both SHR and SCR are GRAS family proteins that are present in partially overlapping domains within the root. In the areas of the root where the expression of the SHR and SCR proteins does not overlap, these proteins show differences in subcellular localization and the ability to traffic between cells. Comparison of transcription with protein localization shows that SHR protein moves from the stele into the surrounding ground tissue. This is not true for SCR. The SHR protein is present both in the cytoplasm and nuclei of stele cells; whereas SCR is restricted to nuclei. As a way of determining what sequences within SHR and SCR are responsible for these differences, we have performed structure/function analysis of both the SHR and SCR proteins. We have identified a domain within SCR that is required for nuclear localization both in the stele and the ground tissue. Surprisingly this domain is independent of the predicted nuclear localization signal. We have also identified multiple regions within SHR that are required for proper subcellular localization and movement of the protein. Significantly, addition of these domains to SCR are able to affect subcellular localization and in some instances confer movement.
SEAN CUTLER
University of Toronto, Canada
Location: Science Library, Rm 240
Day/Date: Thursday, March 16, 2006
Time: 10:10am
Title:
"Strain Selective Drugs: Exploiting Natural
Variation in Chemical Genomics "
Abstract:
Natural genetic variation within a species can be documented at many levels of analysis ranging from simple “aphenotypic” molecular polymorphisms to large scale differences in development such as flowering time. One facet of natural variation explored primarily in humans is pharmacogenetic variation, a clinically important from of inter-individual variation in drug sensitivity. We reasoned that if pharmacogenetic variation is biologically pervasive it could be used to identify genetic factors that modulate drug sensitivity in model systems. To survey pharmacogenetic variation in Arabidopsis, several geographically diverse ecotypes were subjected to the same chemical genetic screen of ~13,500 small molecules library to identify compounds that show differential effects on hypocotyl cell elongation. This screen uncovered 5 loci that act as simple Mendelian traits to modify drug sensitivity.
As one example of the mechanism of pharmacogenetic variation in plants, I will describe our work on hypostatin, a new small molecule inhibitor of cell expansion that ~25% of Arabidopsis isolates are naturally resistant to. Genetic analysis, map based cloning and biochemical analyses have shown that hypostatin resistant strains carry recessive mutations in HYR1, a glycosyl-transferase that converts hypostatin from a pro-drug into an activated form by glycosylation. Intriguingly, HYR1 is part of a large superfamily of enzymes called the UGT-family that are important pharmacogenetic factors in humans. Thus, inter-specific variation in UGT function acts to modulate drug sensitivity across biological kingdoms suggesting that Arabidopsis may be a good model for exploring the mechanisms of pharmacogenetic variation.
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