Rhythmicity of TOR (Target of Rapamycin) Activity Supports Circadian Function in <i>Neurospora crassa</i>
Bibliographic record
Abstract
Circadian (24 h) rhythmicity is a nearly-ubiquitous property of eukaryotic cells, and the mechanisms that generate this rhythmicity have been studied in a number of organisms for many years. However, there are still gaps in our understanding of the generation and regulation of rhythms. Although transcription/translation feedback loops (TTFLs) are said to be essential to generating rhythmicity in eukaryotes, there are many examples of rhythmicity seen in organisms without functioning TTFLs. Our lab previously found that two genes that function in the TOR (Target of Rapamycin) pathway, vta and gtr2 , are essential for non-TTFL rhythmicity in the fungus Neurospora crassa. These two mutants were also shown to dampen the output rhythm of spore-formation (conidiation) and the rhythm of the TTFL component protein FRQ, and dampen the amplitude of the underlying oscillator in strains with functioning TTFLs. Therefore, we are interested in the role of TOR in generating and/or sustaining rhythmicity in both the presence and absence of a functioning TTFL. Here we report the development and validation of an improved assay for TOR activity in Neurospora , and using this assay we demonstrate that TOR activity displays circadian rhythmicity in strains with functioning TTFLs. The period of TOR rhythmicity is affected by a long-period mutation in a TTFL component ( frq 7 ), and the TOR rhythm is dampened in the vta and gtr2 knockouts. The mean level of TOR activity (mesor) in the vta and gtr2 knockout mutants is within the range of the TOR rhythm in wild type, indicating that it is rhythmicity of TOR, not a constant level of activity, that is required to sustain output rhythmicity. These results establish Neurospora as a valuable model for investigating the role of TOR in circadian rhythmicity and implicate TOR activity as a rhythmic state variable of the circadian system.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".