A Compensated Clock: Temperature and Nutritional Compensation Mechanisms Across Circadian Systems.

Circadian rhythms are ∼24-h biological oscillations that enable organisms to anticipate daily environmental cycles, so that they may designate appropriate day/night functions that align with these changes. The molecular clock in animals and fungi consists of a transcription-translation feedback loop, the plant clock is comprised of multiple interlocking feedback-loops, and the cyanobacterial clock is driven by a phosphorylation cycle involving three main proteins. Despite the divergent core clock mechanisms across these systems, all circadian clocks are able to buffer period length against changes in the ambient growth environment, such as temperature and nutrients.

Alignment of Synchronized Time-Series Data Using the Characterizing Loss of Cell Cycle Synchrony Model for Cross-Experiment Comparisons.

Investigating the cell cycle often depends on synchronizing cell populations to measure various parameters in a time series as the cells traverse the cell cycle. However, even under similar conditions, replicate experiments display differences in the time required to recover from synchrony and to traverse the cell cycle, thus preventing direct comparisons at each time point. The problem of comparing dynamic measurements across experiments is exacerbated in mutant populations or in alternative growth conditions that affect the synchrony recovery time and/or the cell-cycle period.

The parasite intraerythrocytic cycle and human circadian cycle are coupled during malaria infection.

During infections with the malaria parasites , patients exhibit rhythmic fevers every 48 h. These fever cycles correspond with the time the parasites take to traverse the intraerythrocytic cycle (IEC). In other species that infect either humans or mice, the IEC is likely guided by a parasite-intrinsic clock [Rijo-Ferreira, , 746-753 (2020); Smith .

Nutritional compensation of the circadian clock is a conserved process influenced by gene expression regulation and mRNA stability.

Compensation is a defining principle of a true circadian clock, where its approximately 24-hour period length is relatively unchanged across environmental conditions. Known compensation effectors directly regulate core clock factors to buffer the oscillator's period length from variables in the environment. Temperature Compensation mechanisms have been experimentally addressed across circadian model systems, but much less is known about the related process of Nutritional Compensation, where circadian period length is maintained across physiologically relevant nutrient levels.

PRD-2 directly regulates and counteracts nonsense-mediated decay in the Neurospora circadian clock.

Circadian clocks in fungi and animals are driven by a functionally conserved transcription-translation feedback loop. In , negative feedback is executed by a complex of Frequency (FRQ), FRQ-interacting RNA helicase (FRH), and casein kinase I (CKI), which inhibits the activity of the clock's positive arm, the White Collar Complex (WCC). Here, we show that the () gene, whose mutation is characterized by recessive inheritance of a long 26 hr period phenotype, encodes an RNA-binding protein that stabilizes the transcript, resulting in CKI protein levels sufficient for normal rhythmicity.

An intrinsic oscillator drives the blood stage cycle of the malaria parasite .

The blood stage of the infection of the malaria parasite exhibits a 48-hour developmental cycle that culminates in the synchronous release of parasites from red blood cells, which triggers 48-hour fever cycles in the host. This cycle could be driven extrinsically by host circadian processes or by a parasite-intrinsic oscillator. To distinguish between these hypotheses, we examine the cycle in an in vitro culture system and show that the parasite has molecular signatures associated with circadian and cell cycle oscillators.

Evaluating the circadian rhythm and response to glucose addition in dispersed growth cultures of Neurospora crassa.

Work on the filamentous fungus Neurospora crassa has contributed to or pioneered many aspects of research on circadian clock mechanism, a process that is functionally conserved across eukaryotes. Biochemical assays of the fungal circadian clock typically involve growth in liquid medium where Neurospora forms a spherical ball of submerged mycelium. Here, we revive a method for dispersed growth of Neurospora in batch culture using polyacrylic acid as an additive to the medium.

The Third International Symposium on Fungal Stress - ISFUS.

Stress is a normal part of life for fungi, which can survive in environments considered inhospitable or hostile for other organisms. Due to the ability of fungi to respond to, survive in, and transform the environment, even under severe stresses, many researchers are exploring the mechanisms that enable fungi to adapt to stress. The International Symposium on Fungal Stress (ISFUS) brings together leading scientists from around the world who research fungal stress.

The cell-cycle transcriptional network generates and transmits a pulse of transcription once each cell cycle.

Multiple studies have suggested the critical roles of cyclin-dependent kinases (CDKs) as well as a transcription factor (TF) network in generating the robust cell-cycle transcriptional program. However, the precise mechanisms by which these components function together in the gene regulatory network remain unclear. Here we show that the TF network can generate and transmit a "pulse" of transcription independently of CDK oscillations.

Layers of regulation of cell-cycle gene expression in the budding yeast Saccharomyces cerevisiae.

In the budding yeast Saccharomyces cerevisiae, transcription factors (TFs) regulate the periodic expression of many genes during the cell cycle, including gene products required for progression through cell-cycle events. Experimental evidence coupled with quantitative models suggests that a network of interconnected TFs is capable of regulating periodic genes over the cell cycle. Importantly, these dynamical models were built on transcriptomics data and assumed that TF protein levels and activity are directly correlated with mRNA abundance.

Reconciling conflicting models for global control of cell-cycle transcription.

Models for the control of global cell-cycle transcription have advanced from a CDK-APC/C oscillator, a transcription factor (TF) network, to coupled CDK-APC/C and TF networks. Nonetheless, current models were challenged by a recent study that concluded that the cell-cycle transcriptional program is primarily controlled by a CDK-APC/C oscillator in budding yeast. Here we report an analysis of the transcriptome dynamics in cyclin mutant cells that were not queried in the previous study.

Connecting virulence pathways to cell-cycle progression in the fungal pathogen Cryptococcus neoformans.

Proliferation and host evasion are critical processes to understand at a basic biological level for improving infectious disease treatment options. The human fungal pathogen Cryptococcus neoformans causes fungal meningitis in immunocompromised individuals by proliferating in cerebrospinal fluid. Current antifungal drugs target "virulence factors" for disease, such as components of the cell wall and polysaccharide capsule in C.

Investigating Conservation of the Cell-Cycle-Regulated Transcriptional Program in the Fungal Pathogen, Cryptococcus neoformans.

The pathogenic yeast Cryptococcus neoformans causes fungal meningitis in immune-compromised patients. Cell proliferation in the budding yeast form is required for C. neoformans to infect human hosts, and virulence factors such as capsule formation and melanin production are affected by cell-cycle perturbation.

The Local Edge Machine: inference of dynamic models of gene regulation.

We present a novel approach, the Local Edge Machine, for the inference of regulatory interactions directly from time-series gene expression data. We demonstrate its performance, robustness, and scalability on in silico datasets with varying behaviors, sizes, and degrees of complexity. Moreover, we demonstrate its ability to incorporate biological prior information and make informative predictions on a well-characterized in vivo system using data from budding yeast that have been synchronized in the cell cycle.