Biomedical subjects

Patricia L Lakin-Thomas

Publications and source records attributed to Patricia L Lakin-Thomas.

5 recordsLinked to original sources

PubMed2006

Circadian clock genes frequency and white collar-1 are not essential for entrainment to temperature cycles in Neurospora crassa.

The fungus Neurospora crassa is a model system for investigating the mechanism of circadian rhythmicity, and the core of its circadian oscillator is thought to be a transcription/translation feedback loop involving the products of the frq (frequency), wc-1 (white-collar-1) and wc-2 (white-collar-2) genes. Several reports of rhythmicity in frq and wc null mutants have raised questions about how central the FRQ/WC loop is to the circadian system of Neurospora. Several research groups have attempted to answer this question by looking for entrainment of the conidiation banding rhythm in frq null mutants. Because the frq mutants are blind to light and cannot be entrained to light/dark cycles, these groups have used symmetric temperature cycles of equal-duration cool and warm phases to entrain the rhythm. Under these conditions, the direct effects of temperature on conidiation (masking effects) can compromise observations of the endogenous rhythm. I have reexamined this question by using short heat pulses to clearly separate masking from endogenous rhythms, and I have assayed entrainment in both frq and wc-1 null mutants. I found similar patterns of entrainment in the wild type and both mutant strains. Strong masking effects were found in the frq mutant but not in the wc-1 mutant. I conclude that a rapidly damping temperature-entrainable oscillator is present in the null mutants. A single temperature-entrainable oscillator may drive the conidiation rhythm in all strains, and additional properties such as light sensitivity and temperature compensation may be conferred by the intact FRQ/WC loop in the WT strain.

Circadian Rhythm↗

PubMed2006

New models for circadian systems in microorganisms.

Microorganisms provide important model systems for studying circadian rhythms, and they are overturning established ideas about the molecular mechanisms of rhythmicity. The transcription/translation feedback model that has been accepted as the basis of circadian clock mechanisms in eukaryotes does not account for old data from the alga Acetabularia demonstrating that transcription is not required for rhythmicity. Moreover, new results showing in vitro rhythmicity of KaiC protein phosphorylation in the cyanobacterium Synechococcus, and rhythmicity in strains of the fungus Neurospora carrying clock gene null mutations, require new ways of looking at circadian systems.

Acetabularia↗

PubMed2006

Transcriptional feedback oscillators: maybe, maybe not...

The molecular mechanism of circadian rhythmicity is usually modeled by a transcription/translation feedback oscillator in which clock proteins negatively feed back on their own transcription to produce rhythmic levels of clock protein mRNAs, which in turn cause the production of rhythmic levels of clock proteins. This mechanism has been applied to all model organisms for which molecular data are available. This review summarizes the increasing number of anomalous observations that do not fit the standard molecular mechanism for the model organisms Acetabularia, Synechococcus, Drosophila, Neurospora, and mouse. The anomalies fall into 2 classes: observations of rhythmicity in the organism when transcription of clock genes is held constant, and rhythmicity in the organism when clock gene function is missing in knockout mutants. It is concluded that the weight of anomalies is now so large that the standard transcription/translation mechanism is no longer an adequate model for circadian oscillators. Rhythmic transcription may have other functions in the circadian system, such as participating in input and output pathways and providing robustness to the oscillations. It may be most useful to think in terms of a circadian system that uses a noncircadian oscillator consisting of metabolic feedback loops, which acquires its circadian properties from additional regulatory molecules such as the products of canonical clock genes.

Acetabularia↗

PubMed2004

Circadian rhythms in microorganisms: new complexities.

Recent advances in understanding circadian (daily) rhythms in the genera Neurospora, Gonyaulax, and Synechococcus are reviewed and new complexities in their circadian systems are described. The previous model, consisting of a unidirectional flow of information from input to oscillator to output, has now expanded to include multiple input pathways, multiple oscillators, multiple outputs; and feedback from oscillator to input and output to oscillator. New posttranscriptional features of the frq/white-collar oscillator (FWC) of Neurospora are described, including protein phosphorylation and degradation, dimerization, and complex formation. Experimental evidence is presented for frq-less oscillator(s) (FLO) downstream of the FWC. Mathematical models of the Neurospora system are also discussed.

Animals↗

PubMed2004

Time-lapse analysis of the circadian rhythms of conidiation and growth rate in neurospora.

The filamentous fungus Neurospora crassa has frequently served as a model organism for the study of circadian rhythms through its ability to form conidial spores on a daily basis. This phenomenon leaves a spatial pattern of conidiation bands along a solid surface of agar after several days of growth. Using time-lapse video, the authors have quantified the rate of conidiation. They have found that conidia do not form at a specified lag time after the growth front is laid down, but rather the band region tends to simultaneously develop over a short time frame. This produces a sharp peak when the conidiation rate is plotted against time. In addition, the authors used time-lapse video to assay growth rate with greater accuracy than previously reported. It is usually assumed that Neurospora's rate of growth is constant, and this assumption of linear growth has been used extensively to determine period and phase of the conidiation circadian rhythm. The authors have confirmed an earlier report of nonlinear growth rate and have shown that the growth rate varies by a factor of about 2 with each circadian cycle. They have demonstrated that the errors in calculating times of conidiation peaks are maximally 1 to 2 h if linearity is assumed. The conidiation rate and growth rate rhythms are not apparent under conditions (using mutants or high or low temperatures) where the spatial banding rhythm is not observed. In light/dark entraining conditions, the conidiation rate and growth rate rhythms maintain the same phase relationship in different T-cycles. These data are consistent with the hypothesis that the growth rate rhythm is a consequence of the conidiation rate rhythm.

Biological Clocks↗