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Discovery of the effect of telomeres on chromosomes.


DNA, in humans, or in any eukaryotic cells, are linear in shape. However, the endings of DNA strands are vulnerable to degradation, situation similar to a shoelace. Then what do our cells do to protect DNA? 2009’s Nobel Prize in Physiology or Medicine is awarded to three scientists who have solved

a major problem in biology: how the chromosomes can be copied in a complete way during cell divisions and how they are protected against degradation. The solution is to be found in the ends of the chromosomes - the telomeres - and in an enzyme that forms them - telomerase When a cell is about to divide, the DNA molecules, which contain the four bases that form the genetic code, are copied, base by base, by DNA polymerase enzymes. However, for one of the two DNA strands, a problem exists in that the very end of the strand cannot be copied. Therefore, the chromosomes should be shortened every time a cell divides - but in fact that is not usually the case. In the early of research, when studying the chromosomes of Tetrahymena, a unicellular ciliate organism, a DNA sequence that was repeated several times at the ends of the chromosomes was identified. The function of this sequence, CCCCAA, was unclear. At the same time, Jack Szostak had


made the observation that a linear DNA molecule, a type of minichromosome, is rapidly degraded when introduced into yeast cells. Later, from the DNA of Tetrahymena, the CCCCAA sequence was isolated. Szostak coupled it to the minichromosomes and put them back into yeast cells. The results were striking - the telomere DNA sequence protected the minichromosomes from degradation. As telomere DNA from one organism, Tetrahymena, protected chromosomes in an entirely different one, yeast, this demonstrated the existence of a previously unrecognized fundamental mechanism. Later on, it became evident that telomere DNA with its characteristic sequence is present in most plants and animals, from amoeba to man.

Telomerase Enzyme telomerase consists of RNA as well as protein. The RNA component turned out to contain the CCCCAA sequence. It serves as the template when the telomere is built, while the protein component is required for the construction work, i.e. the enzymatic activity. Telomerase extends telomere DNA, providing a platform that enables DNA polymerases to copy the entire length of the chromosome without missing the very end portion. Telomeres delay ageing of the cell Later on, researchers found that ageing of human cells is delayed by telomerase. It is now known that the DNA sequence in the telomere attracts proteins that form a protective cap around the


fragile ends of the DNA strands. Application Most normal cells do not divide frequently, therefore their chromosomes are not at risk of shortening and they do not require high telomerase activity. In contrast, cancer cells have the ability to divide infinitely and yet preserve their telomeres. How do they escape cellular ageing? One explanation became apparent with the finding that cancer cells often have increased telomerase activity. It was therefore proposed that cancer might be treated by eradicating telomerase. Several studies are underway in this area, including clinical trials evaluating vaccines directed against cells with elevated telomerase activity. Bullet points ď Ź Telomere helps chromosomes to divide accurately, thus essential to the health of cells ď Ź Telomerase makes telomere


Interesting research results ď Ź Children with shorter telomere length are more susceptible


towards catching a cold ď Ź If telomeres are allowed to shorten, cells struggle to multiply properly. This makes it tough to rebuild and repair bodily tissue. Shortened telomeres open the door to disease. ď Ź Telomere deterioration is linked to many common symptoms and health conditions, many of which are the precursors of diseases that are not presumed to be related. High blood pressure, high levels of triglycerides and high blood sugar levels


Discovery of Biology – Blue light Waking up early for school, struggling to stay awake in morning assembly, they seem to be the most common problem for students. Well, not anymore! Researchers at Rensselaer Polytechnic Institute have just found out the solution to all these troubles---Blue Light. As a matter of fact, the blue light is just nothing high-tech or complicated, it is just light that provide blue visual sensation. For example, the blue sky. The research shows that sleepiness is cause by the miscommunication between your body internal clock and the alarm clock. If you wake up at 6:30 in the morning, your internal clock might only be 5:00a.m. Therefore, you feel sleepy. The internal clock is actually the Circadian rhythm. It controls the sleeping pattern of your body. The scientists find out that light spectrum, especially blue, affect our sleeping pattern. By exposing our eyes 2 hours before our bodies naturally wake up will advance our internal clock. For example, I naturally wake up at 10 a.m., but during school day, I need to wake up at 6 a.m. At 8 a.m. which is 2 hours before I naturally wake up, I need to expose my eyes in blue light so that I won’t feel that sleepy during the lessons. This discovery is very useful in daily life since it can improve our sleeping quality and thus, working efficiency. Goggles are provided so that when users get up in the morning, they can wear them to prevent blue light source exposed to their eyes too early. Then, later in the morning, when it is approximately 2 hours before you naturally wake up, users can take off the


goggles and be exposed to blue light. For example, blue screens in computers. This is a huge milestone for humans, the research found by Rensselaer Polytechnic Institute solve a huge inconvenience in our lives. By getting blue light at the right time, it can change our sleeping pattern. Especially for shift workers and people with sleep disorder.


GREEN FLUORESCENT PROTEIN Introduction Green Fluorescent Protein (GFP) and GFP-like proteins have become the microscope of the twenty-first century. Every month more than 200 papers are published reporting yet another way GFP has been put to work. In most cases, GFP can be used in a way very similar to a microscope; it can show us when a protein is made, and what its movements are.

In honor of the 2008 Nobel Prize in Chemistry, the whole October 2009 issue of Chemical Society Reviews (Vol. 38, pp. 2813-2963) is devoted to GFP. This is an excellent resource for anyone wanting more detailed information about GFP than is presented in this module.

Aequorea Bioluminescence

Green Fluorescent Protein (GFP) has existed for more than one hundred and sixty million years in one species of jellyfish, Aequorea victoria. The


protein is found in the photoorgans of Aequorea. GFP is not responsible for the glow often seen in pictures of jellyfish - that "fluorescence" is actually due to the reflection of the flash used to photograph the jellies. Aequorea victoria Aequorea victoria photoorgans

The crystal jellyfish (Aequorea victoria) has about three hundred photoctyes located on the edge of its umbrella, when stimulated they give off green light Aequorea victoria photocytes are located on the edge of the umbrella. The image shows a microscopic view of some photocytes. The central photograph shows the bioluminescence of the photocytes, while the right hand image shows the jellyfish under visible light. The blue in the photograph on the right is not due to bioluminescence or fluorescence, it is due to visible light reflection. In the absence of GFP, aequorin gives off blue light upon binding calcium; however, in the jellyfish, radiationless energy transfer occurs.

Upon binding calcium, aequorin generates an electronically excited product that undergoes radiationless energy transfer (blue arrow) to the GFP fluorescent state, which emits the green light (509 nm)


Structure of Green Fluorescent protein GFP has a typical beta barrel structure, consisting of eleven β-sheets with six alpha helix(s) containing the covalently bonded chromophore 4-(phydroxybenzylidene)imidazolidin-5-one (HBI) running through the center. The beta barrel structure is a nearly perfect cylinder,42Å long and 24Å in diameter, creating what is referred to as a “β-can” formation. HBI is nonfluorescent in the absence of the properly folded GFP scaffold and exists mainly in the unionized phenol form in wtGFP.[citation needed] Inward-facing sidechains of the barrel induce specific cyclization reactions in the tripeptide Ser65–Tyr66–Gly67 that induce ionization of HBI to the phenolate form and chromophore formation.

GFP molecules drawn in cartoon style, one fully and one with the side of the beta barrel cut away to reveal the chromophore (highlighted as ball-and-stick). From PDB 1GFL.


GFP ribbon diagram. From PDB 1EMA.

This process of post-translational modification is referred to as maturation. The hydrogen-bonding network and electron-stacking interactions with these sidechains influence the color, intensity and photostability of GFP and its numerous derivatives. The tightly packed nature of the barrel excludes solvent molecules, protecting the chromophore fluorescence from quenching by water.

Application of Green Fluorescent protein 1. Fluorescence Microscopy The availability of GFP and its derivatives has thoroughly redefined fluorescence microscopy and the way it is used in cell biology and other biological disciplines. For instance, ďƒ˜ GFP is used to express the protein in small sets of specific cells. This allows researchers to optically detect specific types of cells in vitro (in a dish), or even in vivo (in the living organism). ďƒ˜ A novel possible use of GFP includes using it as a sensitive monitor of intracellular processes via an eGFP laser system made out of a human embryonic kidney cell line. ďƒ˜ GFP is used label and track cancer cells have metastasis, the cells spread to

2. Transgenic pets

widely in cancer research to cancer cells. GFP-labeled been used to model process by which cancer distant organs.


Mice expressing GFP under UV light (left & right), compared to normal mouse

(center) GloFish, the first pet sold with these proteins artificially present.

3. GFP in fine art Julian Voss-Andreae, a German-born artist specializing in "protein sculptures," created sculptures based on the structure of GFP, including the 1.70 m (5'6") tall "Green Fluorescent Protein" (2004) and the 1.40 m

(4'7") tall "Steel Jellyfish" (2006).


Machinery Regulating Vesicle Traffic, a Major Transport System in our Cells INTRODUCTION The 2013 Nobel Prize in Physiology or Medicine is awarded to Dr. James E. Rothman, Dr. Randy W. Schekman and Dr. Thomas C. S端dhof for their discoveries of machinery regulating vesicle traffic, a major transport system in our cells. Each cell in our bodies has a complex organization where specific cellular functions are separated into different compartments called organelles. Molecules produced in the cell are packaged in vesicles and transported with special and temporal precision to the correct locations within and outside the cell. This is called cellular compartmentalization. Mysteries of cellular compartmentalization have long intrigued scientists. THE PROCESS OF DISCOVERY Dr. Randy W. Schekman discovered genes encoding proteins that are key regulators of vesicle traffic. Comparing normal with genetically mutated yeast cells in which vesicle traffic was disturbed, he identified genes that control transport to different compartments and to the cell surface. Dr. James E. Rothman discovered that a protein complex enables vesicles to fuse with their target membranes. Proteins on the vesicle bind to specific complementary proteins on the target membrane, ensuring that the vesicle fuses at the right location and that cargo molecules are delivered to the correct destination. Dr. Thomas C. S端dhof studied how signals are transmitted from one nerve cell to another in the brain, and how calcium (Ca2+) controls this process. He identified the molecular machinery that senses calcium ions and converts this information to vesicle fusion, thereby explaining how temporal precision is achieved and how vesicles can be released on command. IMPORTANCE OF THE DISCOVERY The work of Rothman, Schekman and S端dhof has unraveled machinery that is essential for routing of cargo in cells in organisms as distantly related as yeast and man. These discoveries have had a major impact on our understanding of how molecules are correctly sorted to precise locations in cell. In the light of this, it comes as no surprise that defects at any number of steps in the machinery controlling vesicle transport and fusion are associated with disease. Vesicle transport and fusion is essential for physiological processes ranging from


control of nerve cell communication in the brain to immunological responses and hormone section. Deregulation of the transport system is associated with disease in these areas. For example, metabolic disorders such as type 2 diabetes are characterized by defects in both insulin secretion from pancreatic beta-cells and insulin-mediated glucose transporter translocation in skeletal muscle and adiposetissue. Furthermore, immune cells in our bodies rely on functional vesicle trafficking and fusion to send out substances including cytokines and immunologic effector molecules that mediate innate and adaptive immune responses. CONCLUSION The discoveries of the Dr. James E. Rothman, Dr. Randy W. Schekman and Dr. Thomas C. S端dhof illustrated one of the fundamental and important processes of eukaryotic cells. Vesicle fusion transport and fusion occurs in a same way in yeast and men. Without the precise organization, the cells would be very chaotic and our bodies would not be able to function properly. The discovery of this exquisite method of organization in cells can certainly facilitate other discoveries of medical science. It can also increase our understanding of how cellular communication occurs to sort molecules to precise locations within and outside the cell.



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