block 10-circadian rhythms Flashcards

(46 cards)

1
Q

Circadian clocks

A

-organised by an endogenous clock

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

temporal coordination

A

Temporal coordination refers to the ability of biological systems to time internal processes so they occur at the right moment — often in alignment with environmental cues like light, temperature, or time of day.

In plants, components of the photosynthetic machinery are synthesised at the time when they are needed – in the morning
- another reason why having a clock is important

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is temporal separation of incompatible processes?

A

-Temporal separation is a strategy where biological processes that cannot occur simultaneously (due to conflicting conditions) are separated in time rather than space. This ensures that each process can function optimally without interference.
-Cyanobacteria carry out both photosynthesis (which produces oxygen) and nitrogen fixation (which requires a low-oxygen environment).
However, oxygen is toxic to the enzyme that fixes nitrogen, so these two processes are incompatible.
To solve this, cyanobacteria use temporal separation — they do photosynthesis during the day, when light is available, and nitrogen fixation at night, when oxygen levels are lower.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

control of metabolism

A
  • metabolism is rhytmic

-Clock mutant mice (no circadian rhythm) have a tendency to gain weight due to abnormal regulation of appetite and fuel utilisation
-why having a clock is important

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

avodance of predators in normal vs mutant mice

A

A functional circadian clock helps animals stay active at appropriate times of day — often when it’s safer and predators are less active.

🧪 Study Example (US chipmunk experiment):

Normal chipmunks (with a working internal clock) stayed in burrows at night and were active during the day.

Mutant chipmunks (with a disrupted clock) emerged at night — and were heavily preyed on by nocturnal predators like weasels.

📌 Conclusion:
The circadian clock improves survival by syncing behavior (like feeding or hiding) to the safest time of day. Without it, animals may become active during dangerous periods, increasing their risk of predation.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

orientation

A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

changes of season due to clock

A

-breeding is seasonal

-some animals change coat colour in the winter
-dinal point on lecture slide to all the reason above why having a circadian clock is important

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

circadian variation in the expression of diseases

A

Many diseases and symptoms show daily (circadian) rhythms. For example, pain sensitivity is often higher in the morning, and asthma attacks are more common at night. This is because body functions like hormone levels, inflammation, and nerve activity change over a 24-hour cycle
-usefful for smart medicine= target critical times

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

situations where the body clock is out of synchrony with the environment

A
  • After travelling through time zones (jet lag)
  • When working rotating shifts
  • When persistently having to re-set endogenous
    timing to conform to social obligations (school,
    work, socializing)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

jet-lag and shift-work symptoms

A

Short term=

  • disrupted sleep
  • loss of appetite
  • gastro-intestinal problems
  • difficulty concentrating* feeling disorientated
  • memory problems* clumsiness
  • lack of energy
  • irritability

long term= INCREASED RISK OF :▪ cancer▪ cardiovascular disease▪ depression

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

how can we study the circadian clocks in animals?

A

We start by identifying a measurable biological rhythm — such as hormone levels, body temperature, or activity patterns.

🧪 This often involves collecting biological samples (e.g., blood, urine, or buccal cells) and tracking physiological parameters over time.

📌 Note:

Best suited for larger animals.

Can be invasive, technically complex, and expensive, especially for long-term monitoring.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

locomotor activity rhythm in small rodents and drosophila melanogaster

A

In small rodents or fruit flies (Drosophila), we can measure how much they move during light and dark periods.

These movement patterns form a clear rhythmic pattern (recorded in something called an actogram) — showing when they’re active or resting, both under normal light/dark cycles (LD) and even in constant darkness (DD

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

properties of the clock 1

A

Circadian clocks keep ticking even in constant conditions (e.g. constant darkness or constant light), a phenomenon known as free-running.

🔁 The internal rhythm has a period close to, but not exactly 24 hours.

💡 Key Points:

Each species has a characteristic range of periods, not a fixed value.

There’s natural variation in this period across individuals in both wild and lab populations.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

normal patterns observed in actogram

A

An actogram is a visual representation of an animal’s activity over time.

🌀 Under normal light-dark (LD) cycles:

Animals show entrained rhythms, meaning they are active at the same time each day (e.g., nocturnal animals active during dark phase).

Activity starts and stops in sync with the external light cues.

🌑 Under constant conditions (e.g. constant darkness, DD):

The rhythm becomes free-running — it continues without light cues but shifts slightly each day, reflecting the animal’s internal clock (e.g., activity starts a little earlier or later each day).

✅ This shift helps demonstrate that the rhythm is endogenous (generated internally), not just a response to external cues.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

free run patterns observed on the actogram

A

When light cues are removed and the animal is kept in constant darkness, it follows its internal circadian rhythm (usually not exactly 24 hours).

For example, if an animal has a 23.5-hour internal clock, its activity will start a bit earlier each day.

This appears in the actogram as a diagonal drift — each line of activity starts a little earlier than the one above.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

properties of the clock 2

A

Entrainable. Through sensory modalities or even through
bespoke ‘clock molecules’ (for instance blue-light sensitive
proteins called cryptochromes) the clock is able to detect an
external rhythmic variable (light, temperature, vibrations,
food, social interactions, etc.). The clock aligns its period to it
and assumes a defined phase relationship towards it. Once
entrained, the clock tends to resist a change in the cycling
condition, before entraining to the new cycle. This proves
that entrainment is not simply synchronisation but
additionally a form of ‘memory’ deriving from two
oscillators resonating together. The external cycling stimulus
is called a Zeitgeber, which means time giver in German.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

propertie of the clock 2 on the actogram-CHEAT SHEET I NECESSARY

A

📊 What You’d See on the Actogram:
1. Before Entrainment – Free-Running Rhythm
If the animal is in constant darkness (DD), you’ll see a diagonal drift in activity (not quite 24 hrs).

This shows its natural circadian rhythm is slightly off (e.g., 23.7 or 24.3 hrs).

  1. Entrainment Begins
    Once the animal is exposed to a regular external cue (e.g. 12 hours light / 12 hours dark, or daily feeding time), its internal clock adjusts.

On the actogram, the diagonal drift stops.

Activity lines up vertically, showing that the rhythm is now stable and synced to the external cycle.

  1. Phase Relationship
    The activity now begins at a consistent time relative to the Zeitgeber — for instance, just after lights-off.

This steady timing is the phase relationship between the internal clock and the external cue.

  1. After a Zeitgeber Shift – Transient Days
    If the Zeitgeber (e.g. light timing) suddenly changes, the rhythm doesn’t shift instantly.

Instead, you’ll see a few days of gradual adjustment on the actogram — this is called a transient phase.

The clock “resists” change at first, showing it’s not just reacting immediately — it has a kind of memory.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

properties of the clock 3

A

Temperature compensation. The circadian clock
measures time independently of temperature. The Q10
temperature coefficient is a measure of the rate of
change of a biochemical reaction as a consequence of
increasing the temperature by 10 °C. For most
biochemical reactions, Q10 = 2; for circadian period
length: Q10 ~ 1 (0.8 – 1.4). This is very important
especially for poikilotherms as the subjective perception
of time would be too variable to be useful.
-this shows circadian clock is barelt affected by temperature as the change in q1 is small

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

how would you observe property 3 on the circadian clock

A

On the actogram, you would see no shift in activity timing, even as the temperature fluctuates.

The activity bars will stay aligned in the same pattern each day, maintaining their regular timing.

If the temperature changes (e.g., a warm day followed by a cool night), there would be no observable shift in the time when activity begins — the rhythm remains consistent.

20
Q

the genetic approcah

A

the study of utant genes which may have normal functions, research may better understand normal genes
Strengths
* unbiased
* does not require previous
knowledge
* starting point for
biochemical/molecular studies
Weaknesses
* blind to lethal genes
* blind to epistasis
* cannot solve non-
linearity

21
Q

the genetic analysis of behavior

A

-Genetic analysis of behaviour began seriously in 1960’s, through selection experiments and strain comparisons. The underlying rationale was that behaviour is a quantitative trait, hence cannot be studied at the level of single genes
-drosphila is the perfect model system to study neurogenetics …

22
Q

The godwin model

A

The Goodwin model is a theoretical framework that helps explain how circadian rhythms (or other oscillations in physiology) can be generated. Here’s what you need to know:

Oscillation via Negative Feedback: The model suggests that physiological oscillations (like the circadian cycle) are driven by negative feedback loops. This means that the accumulation of a protein over time will inhibit the gene that produces it, creating a feedback loop.

Example: Protein X (e.g., PER) is produced and increases in concentration, but eventually Protein X inhibits the gene that codes for Protein X. This negative feedback slows down or stops further production of Protein X.

Delay and Cooperativity:

Delay: There’s a time lag between the protein being produced and it inhibiting its own gene, which is a key feature of oscillations (a cycle).

Cooperativity: Multiple proteins or molecules may interact, amplifying the feedback loop and making the system more sensitive or robust.

In simpler terms, the model explains how an oscillation or rhythmic pattern can arise from feedback between proteins that regulate each other over time.

23
Q

per as a pas protein

A

PER is also identified as a PAS protein. PAS proteins (Per-ARNT-Sim domain proteins) are a family of proteins that are involved in circadian rhythms, oxygen sensing, and other biological processes.

PAS proteins play a role in signal transduction and are involved in the regulation of gene expression in response to environmental changes, including the circadian rhythm cycle.

24
Q

Negative feedback loop of PER

A

The PER (Period) protein, which is central to the circadian clock, has been shown to participate in a negative feedback loop that regulates its own expression over time. Here’s a summary of how this works:

PER accumulation: PER protein is produced and accumulates in the cell over a 24-hour cycle, particularly in the evening and night.

Transcriptional regulation: Once enough PER is present, it inhibits the transcription of the PER gene.

Nuclear localization: Late at night, PER moves into the nucleus, where it helps to block its own transcription — a process that’s essential for resetting the clock.

The feedback (inhibition) happens in a time-delayed manner, and the combination of these processes leads to the 24-hour rhythm.

25
TIM
tim: A Key Circadian Clock Gene tim is a newly identified gene essential for regulating circadian rhythms. Flies with a tim⁰ mutation are behaviorally arrhythmic, showing no regular cycles of activity and rest. tim mRNA and Protein Cycling In normal flies, tim mRNA and protein follow a 24-hour cycle. Protein levels peak about six hours after mRNA, similar to the delay seen with per. (meaning there is a 6 hiur delay between the TIM mRNA being made and the TIM protein accumilating) Loss of Molecular Rhythms in tim⁰ Flies In tim⁰ mutants, neither tim nor per shows rhythmic cycling, suggesting that TIM and PER work together to maintain circadian regulation.
26
Per and TIM
they physically interact -are interdependent -without PER, TIM is not able to go in the nucleus -PER needs TIM to be stable otherwise it will be degraded
27
the affect of light on TIM
-Tim is degraded by light
28
per and Tim interaction
During the Day: Both PER and TIM genes are transcribed (their mRNA is made). However, light causes TIM protein to be degraded. Since PER and TIM proteins need each other to be stable and enter the nucleus, PER also cannot accumulate properly. Result: Even though the mRNA for PER and TIM is made during the day, the proteins don’t build up because light breaks down TIM, and without TIM, PER is also unstable. At Night: Light is gone, so TIM is no longer degraded. TIM can now bind to PER, forming a stable PER-TIM complex. This complex is able to accumulate and enter the nucleus. Once in the nucleus, PER and TIM inhibit their own gene expression — this is part of the negative feedback loop that keeps the circadian rhythm going.
29
what regulates per and tim translation and transcription
-phosphorylation
30
what regulates per and tim expression
-they regulate their own expression
31
Role of Cryptochrome (CRY)
CRY Function Divergence In Drosophila (flies): CRY is a blue-light photoreceptor. Light activates CRY → leads to TIM degradation. This allows the clock to reset based on light cues (entrainment). In mammals: CRY is not a photoreceptor. Instead, CRY is a core repressor in the transcriptional feedback loop. It inhibits CLOCK:BMAL1, helping shut down clock gene expression. 🧬 Key Point: CRY has conserved structure but divergent functions — light sensing in flies vs. transcriptional repression in mammals.
32
The Transcription-Translation Feedback Loop (TTL)
Basic process: Positive elements (CLOCK + CYCLE in flies, CLOCK + BMAL1 in mammals) activate the transcription of target genes like per and tim. PER and TIM proteins accumulate, form a complex, and enter the nucleus. There, they inhibit CLOCK/CYCLE or CLOCK/BMAL1, stopping their own expression. Over time, PER/TIM break down, releasing the inhibition and starting a new cycle. This negative feedback creates a roughly 24-hour rhythm in gene expression and protein levels.
33
The Positive Elements of TTL
In flies: CLOCK is the dominant partner: it has a strong activation domain (polyQ motif) and is rhythmically expressed. In mammals: BMAL1 takes the lead: it is rhythmically expressed and has the primary activation domain. Despite the differences in which partner is dominant, both systems rely on heterodimers (CLOCK:CYCLE or CLOCK:BMAL1) to kickstart the transcription of circadian genes.
34
summary
The TTL is conserved between flies and mammals, but components have evolved slightly different roles. CRY is a light sensor in flies, but a transcriptional repressor in mammals. PER and TIM are central to negative feedback in both species. The clock machinery is modular, which helps it adapt to different evolutionary and environmental needs.
35
what is an ebox
An E-box (Enhancer box) is a specific DNA sequence motif: CACGTG It's found in the promoter regions of clock-controlled genes like per and tim. The CLOCK:CYCLE (flies) or CLOCK:BMAL1 (mammals) heterodimer binds to E-boxes. This binding activates transcription of circadian genes. 🕒 So: E-boxes are key sites that drive the rhythmic expression of genes in the TTL.
36
Molecular Constituents of Insect Clocks
nsects (like Drosophila, Anopheles, Apis, etc.) all have circadian clocks based on the TTL. But: not all insects use exactly the same set of genes. For example, some insects don’t use TIM, and some use mammal-like CRYs. 👉 This shows evolutionary plasticity in how the same basic architecture is adapted.
37
Four TTL Models in Insects
The Beer & Helfrich-Förster (2020) study outlines four different transcription-translation loops across insect species. Some models use CRY as a repressor, others use TIM, or combinations of PER/CRY/TIM in varying roles. 🧠 Takeaway: the core logic (negative feedback) remains, but molecular players vary.
38
Anatomical Location of the Clock in Mammals
Main clock = Suprachiasmatic Nucleus (SCN) in the hypothalamus. Located just above the optic chiasm (perfect for sensing light input via the retina). SCN acts as a master pacemaker, syncing: Peripheral clocks in organs like the liver, heart, skin, etc. These clocks have autonomous rhythms, but follow SCN timing. 🎯 The SCN is responsible for internal synchrony and the experience of jet lag (delay in re-entraining clocks after timezone shifts)
39
Anatomical Location of the Clock in Flies
Central clock is in seven bilateral groups of neurons in the fly brain: Dorsal Neurons (DN1, DN2, DN3) Lateral Neurons (LNd, s-LNv, l-LNv) LPN (in the posterior brain) The s-LNv and l-LNv neurons release PDF (Pigment Dispersing Factor), which coordinates and synchronizes the clock network.
40
Three fundamental properties of circadian clocks:
Endogenous (~24 h even without external cues) Entrainable (adjusts to Zeitgebers like light) Temperature-compensated (Q10 ≈ 1)
41
Zeitgeber:
An external cue (like light, food, temperature) that entrains the circadian clock. Literally means “time giver” in German.
42
Neurogenetics:
The study of how genes influence neural function and behaviour, especially through genetic mutations or manipulation
43
Konopka and Benzer & per gene:
Discovered period (per) in 1971 via mutants with altered circadian periods. Classified it as part of the core oscillator, since per mutations disrupted rhythmicity itself.
44
Role of TIM in Drosophila
Binds and stabilizes PER at night. Allows it to enter the nucleus and inhibit CLOCK:CYCLE activity. Degraded by light, which helps reset the clock.
45
How many Per genes in mammals?
Three: Per1, Per2, Per3
46
Difference between CRY1-like and CRY2-like molecules:
CRY1-like: Typically stronger repressors, longer circadian period. CRY2-like: Weaker repressors, shorter circadian period. Both inhibit CLOCK:BMAL1, but with different dynamics.