Collaborative Research: Integration of metabolic cues and life cycle decisions in Chlamydomonas

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Single-celled organisms, such as protists and bacteria, inhabit fluctuating environments where nutrient availability isn't always guaranteed. To cope with this "feast or famine" uncertainty, cells have evolved processes that allow them to respond appropriately by growing and dividing when nutrients are present (proliferation), or by becoming dormant and adopting an energy-conserving state when starved (quiescence). This project utilizes a single-celled reference organism, the green alga Chlamydomonas, to investigate how molecular switches that govern proliferation and quiescence are controlled and how they are coordinated to ensure that they don't interfere with each other. Microorganisms like these can accumulate large quantities of valuable compounds, e.g. oils, but only when starved. It is anticipated that knowledge about the molecular switches governing transitions between the states of proliferation and quiescence will allow predictions about how these states can be controlled and engineered. Thus, newly discovered details about these molecular switches provide potential engineering strategies to uncouple high yields of valuable compounds from starvation responses. Students and postdoctoral fellows from the two research locations will collaborate to identify and model the interactions between key regulators of quiescence and proliferation that have counterparts in many other species including plants and animals. The diversity of approaches and quantitative training components prepare the trainees for science careers in industry or academia. The long term goal of this project is to gain a predictive understanding of how nutrient and metabolic cues are integrated into coherent decisions that control life cycle state transitions. In the unicellular green alga Chlamydomonas reinhardtii, two nuclear protein complexes, CHT7-C and RB-C, have been identified that govern the transitions between nutrient-deprivation induced quiescence, cell growth, and commitment to cell division. It is hypothesized that the quiescence regulator CHT7-C, and the cell cycle commitment regulator RB-C form an interlocking transcriptional network that coordinately controls cell growth and division responses to nutrient or metabolic cues. The objectives of this project are to: (1) characterize purified CHT7-C and RB-C complexes in order to define their subunit composition and modifications under different life cycle states; (2) Identify CHT7-C and RB-C target genes followed by generation of a transcriptional network model to observe common nodes that functionally couple the two complexes; (3) combine mutations affecting different components of the two complexes into isogenic lines to obtain synthetic phenotypes that provide insights into function and interrelation of the two complexes in vivo; and (4) build a testable logic switch model and develop quantitative markers to test and revise the model. The collaborative approach taken for studying the interactions between quiescence and cell proliferation regulators is aimed at transforming the understanding of the networks that establish and maintain coordinated global responses to metabolic and nutritional cues.