Project 2 Multiscale spatial and temporal dynamics of yeast colony development Introduction. In living systems, the characteristics of an individual, including traits such as susceptibility to disease or response to therapy, are determined by the coupling of processes that function at different scales of organization. For example, an individual's DNA sequence constrains the molecular networks that govern its cellular states and behaviors, which in turn determine the form and functions of multi-cellular structures. Microorganisms, including the yeast Saccharomyces cerevisiae, are traditionally used as models for investigating basic cellular processes at the unicellular level. However, unicellular organisms can form multi-cellular communities and differentiate into specialized structures to benefit the population. In some wild isolates of S. cerevisiae colonies (which start from a single cell and divide mitotically to become a structure of -10[8] cells) undergo a morphological transition characterized by complex patterns ofwrinkles on the colony surface (Fig. 11). This trait is called the fluffy phenotype. Work by others has shown that fluffy yeast colonies possess many properties of microbial biofilms and are thus directly relevant to health and human disease'. In fluffy colonies, cells are connected by an extracellular matrix and internal hollow channels, which may help exchange nutrients and waste products. While there is some evidence that this morphological development involves nutrientdriven cell state transitions, cell-cell signaling, quorum sensing and cell death^, the exact molecules and in many cases the pathways are largely unknown. The importance of the experimental system: This project seeks to understand how cells establish and maintain spatiotemporal patterns of cell state transitions to form multicellular structures. In our model (yeast fluffy colony formation) a single cell divides a undergoes a series of metabolic and functional transitions to reproducibly self organize into a complex structure of 10 cells. By advancing the conceptual, computational, and technical challeges below, we will develop a general methodology for analyzing complex traits that exhibit morphological phenotypes and can thus be applied to problems as diverse as physical birth defects during development or angiogenesis during tumor growth.
| Shao, Wenguang; Pedrioli, Patrick G A; Wolski, Witold et al. (2018) The SysteMHC Atlas project. Nucleic Acids Res 46:D1237-D1247 |
| Kazantsev, Fedor; Akberdin, Ilya; Lashin, Sergey et al. (2018) MAMMOTh: A new database for curated mathematical models of biomolecular systems. J Bioinform Comput Biol 16:1740010 |
| Mast, Fred D; Herricks, Thurston; Strehler, Kathleen M et al. (2018) ESCRT-III is required for scissioning new peroxisomes from the endoplasmic reticulum. J Cell Biol 217:2087-2102 |
| Pacheco, Derek; Warfield, Linda; Brajcich, Michelle et al. (2018) Transcription Activation Domains of the Yeast Factors Met4 and Ino2: Tandem Activation Domains with Properties Similar to the Yeast Gcn4 Activator. Mol Cell Biol 38: |
| Kim, Seung Joong; Fernandez-Martinez, Javier; Nudelman, Ilona et al. (2018) Integrative structure and functional anatomy of a nuclear pore complex. Nature 555:475-482 |
| Kearney, Paul; Boniface, J Jay; Price, Nathan D et al. (2018) The building blocks of successful translation of proteomics to the clinic. Curr Opin Biotechnol 51:123-129 |
| Lee, Joon-Yong; Choi, Hyungwon; Colangelo, Christopher M et al. (2018) ABRF Proteome Informatics Research Group (iPRG) 2016 Study: Inferring Proteoforms from Bottom-up Proteomics Data. J Biomol Tech 29:39-45 |
| Tuttle, Lisa M; Pacheco, Derek; Warfield, Linda et al. (2018) Gcn4-Mediator Specificity Is Mediated by a Large and Dynamic Fuzzy Protein-Protein Complex. Cell Rep 22:3251-3264 |
| Maixner, Frank; Turaev, Dmitrij; Cazenave-Gassiot, Amaury et al. (2018) The Iceman's Last Meal Consisted of Fat, Wild Meat, and Cereals. Curr Biol 28:2348-2355.e9 |
| Holden, Jennifer M; Koreny, Ludek; Obado, Samson et al. (2018) Involvement in surface antigen expression by a moonlighting FG-repeat nucleoporin in trypanosomes. Mol Biol Cell 29:1100-1110 |
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