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

Telomere helps chromosomes to divide accurately, thus essential to

the health of cells

Telomerase makes telomere

Interesting research results

Children with shorter telomere length are more susceptible

towards catching a cold

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.

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-(p-hydroxybenzylidene)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,

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).

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.

GFP is used widely in cancer research to

label and track cancer cells. GFP-labeled

cancer cells have been used to model

metastasis, the process by which cancer cells

spread to distant organs.

2. Transgenic pets

Mice

expre

ssing

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. Südhof 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. Südhof 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 Südhof 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. Südhof 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.