Read the article titled, “Around the Clock,” pp. 14-20 in the Spring 2014 Bullet

Question

Read the article titled, “Around the Clock,” pp. 14-20 in the Spring 2014 Bulletin of the Howard Hughes Medical Institute on circadian biology. View the videos included on the website. Here is a link:

http://www.hhmi.org/bulletin/spring-2014/around-clock

The two videos include brief cartoon of cells and a 20-minute TEDx lecture by Professor Joseph Takahashi, with information on circadian patterns of gene expression that might be challenging to follow.

Your review should focus on the big picture. Limit your review to approximately 1,250 words.

Explanation / Answer

AROUND THE CLOCK

The biological programs present in life on earth will keep the planet inhabitants on a 24 hour schedule known as circadian rhythm. The tentacles of circadian system can be found around everything and they can be found from plants to flies to humans. Understanding about these circadian rhythms may help us to fix the system when it loses the track of time. The findings by Takahashi revealed that, healthy mice follow a 24 hour schedule of sleeping, eating and exercising even in steady darkness.

Before Takahashi, former investigator Michael Young worked on circadian rhythm in Drosophila melanogaster. They observed genes whose expression cycled around 24 hours and named the genes as timeless and period. The product of the genes entered the nuclei and worked as feeback by controlled the genes which encoded them.

All living organisms developed biological clock to anticipate life (change in light or temperature). The most familiar biological rhythm is sleep-wake. The sleep wake cycles are governed. A young medical student (1938) underwent 40 days in to a cave (artificial cave). On observing his sleep wake cycle, they found out that, for the first week, he woke up by 8A.M. When the doors were shut and when he got isolated, he started waking up close to mid night. During this time of isolation, he underwent fewer biological days than the number of real. His day was about 25.4 h, where as the normal day is of 24 h. When door opened, he started getting up at right time. So, we can say from outside also, some elements are controlling our biological rhythm. Light is a primary synchronizer and is a major synchronizer. Light mediated by our eyes projected down by optic nerves to brain.

This gives raise to some interesting questions, like how this clock works, where the clock is located, is the clock is genetically internal or genes are controlling this clock. The location of biological clock is in brain. Further work showed that the play station is two yellow structures, which are turned out to be biological clock. They have 10,000 cells, each of which contains biological clock.

The further research was done on mouse, to know the genes involved in circadian rhythm. Mouse is having beautiful circadian rhythm, random changes in the genes, will affect rhythm. To study difference between normal and mutated one, a mutant mouse was prepared. The mutant one lost the biological clock. We can sense this through the behavior of mouse. The further investigation focused on location of the gene that might get affected.

The mouse genome is similar to our genome with 20 chromosomes. In mammalian brain cells, they found out that the CLOCK protein and its partner BMAL1 will pair up and they played a role in turning on of Period and cryptochrome genes. The proteins of is per and cry will synthesized outside the nuclei and these two proteins interact, and come back to the cells, inhibit CLOCK and BMAL1 genes when per and cry proteins are reached to a certain level. These proteins interact with each other endlessly and take 24 hours to complete. The CLOCK and BMAL1 peak during each day and the peak of Period and Cryptochrome will be seen each night. The rise and fall of these proteins will turn on and off many other genes throughout our body.

The biological clock can be explained with the thousands of genes are cycling off and on in our body. These regulate metabolism through processing fuel and generating energy, the link between the clock and metabolism can give us the reasoning why humans and animals will eat at the same time everyday or why they feel hungry exactly at the food time and secretes more digestive molecules before the meal time.

The circadian rhythm regulates each day and each cell undergoes this rhythm. Suprechiasmatic nucleus (SCN) is the site of biological clock. Through, 7 day timeplase recording, we can see the proteins fluctuations over time. The further study has been done at single cell level.

When we see skin cells under microscope, each cell oscillates. The clock which exist throughout body, keep the body in rhythm and differs in different organisms. This gives rise to a question, how is clock timing integrated in the brain and throughout body? How brain talks to body.

The answer for the above question came from Derek Parfit (1984),   a scientist who gradually replaced the cells in one body with cells from other body. At this point, when the other cells will overtake the existing cells?. The findings for this came from the experiment on mice, here a chimera was constructed which is a mixture of two other mice. The mixing of two 8 celled stage embryos gave rise to a chimeric mouse. Proportion of wild type to mutant cells determines behavior. When there was a 50% mix, third type of behavior was seen. The integration generated a new behavior.

The use of high throughput genetic technology by Young in Drosophila and use of nascent RNA sequencing by Rosbash has given an insight how the number of genes fluctuate in circadian pattern. Circadian rhythm controls the gene expression. We can say that circadian regulators control the gene expression in cells at two levels, when the gene transcribed into RNA and when RNA is processed and translated to proteins.

Another example we can see in sleeping pattern, how much sleep a normal person gets, it differs with age, conditions. Roenneberg et al., 2013 gave another example in the form of Social Jet lag, which also differs, based on the age. Consequences of jet log can be seen in metabolic, BMI correlated with the social jetlag. When social jet lag is less, BMI will be under 25, but when jet lag gets worse, it pushes BMI to a higher level. The study on 3 groups with 8, 6 and 4 h of sleep for 14 days showed that the loss of sleep showed adverse effect on hormonal production.

We can say ‘’ Keep in synch, get enough sleep, and you will be smarter, thinner and happier”

Related Questions

Navigate

• Browse (All)
• Browse R
• Subjects

Integrity-first tutoring: explanations and feedback only — we do not complete graded work. Learn more.