Biology

Club 2013-2014

Dec 2013 Bulletin Issue #1 Optogenetics

• What are optogenetics?

• Optogenetics and you

Read on to discover

more!:)

Inside:

Have you ever heard about “光遺傳學”???

Optogenetics (光遺傳學) is the science of using light to

stimulate certain responses from cells, groups of cells or

organs within complex biological systems.

Neuroscientists

traditionally study the

function of the brain by

stimulating and

recording the activity of

single nerve cells with

electrodes. The idea of

using light to start or

stop neurons in living animals was proposed some decades ago by the

famous Nobel Prize–winning scientist, Francis Crick. The optogenetic

method was pioneered in 2005 by Boyden and Karl Deisseroth at

Stanford University.

However, what is optogenetics exactly?

Optogenetics is the combination of genetics and optics to control

well-defined events within specific cells of living tissue. It includes the

discovery and insertion into cells of genes that confer light

responsiveness; it also includes the associated technologies for delivering

light deep into organisms as complex as freely moving mammals, for

targeting light-sensitivity to cells of interest, and for assessing specific

readouts, or effects, of this optical control. Both precision in the length

What is Optogenetics?

INTRODUCTION:

of the bursts of light and the

ability to produce bursts of

light with great speed are

essential to the practice of

optogenetics.

Optogenetics involves the use of light to provoke responses from

certain proteins existing as part of complex biological systems. It can also

involve the use of light to invoke responses from single cells, rather than

groups of cells.

READ MORE, KNOW MORE and

LEARN MORE

Continual reading…… Find out more

about the OPTOGENETICS ~~~~~

Over the years, scientists have been trying hard to understand

how our brains work.

However, with limited technology, we human only knew a small

part of this mystery.

In 2002, some scientists discovered a protein that can cause

green algae to move towards or away from light. They later

found out that the protein (channelrhodopsin2 or ChR) is a light

sensitive channel. Blue light causes the channel to open and

enables ion to float in, which activate the nerve cell, while

when given no light, the channel will be closed. They saw the

potential of it and wondered if the protein can control the

movement of the algae with light,

if they get the protein into the

nerve cell, they can control the

nerve activities in the brain.

In August 2005, Ed Boyden and Feng Zhang have successfully

tried the technology on mammal nerve system. The most

famous example is the optogenetic were used to

control the eyes’ behavior of a monkey. With

inserting a certain ChR, when the blue light is on,

the monkey eyed on the target faster than usual.

In 2006 the word “optogentic” was even coined!

This discovery has been a huge

milestone for mankind. It has

made us easier to understand our

brain and even will be able to cure

Parkinson’s disease or other

metal illness. For your information, it hasn’t been used in a dark

evil way like what you see in the movies, humans are not

DOOMED, please don’t worry.

Living things responding to light?! So strange…

Actually, living organisms with phototropic response are everywhere! For

example plants, which usually grows towards the light.

And of course we humans, where the light-sensitive cell on the retina of

our eyes detect light.

So you are now more familiar with phototropic response, but how does

it work? In most cases, it involves light-sensitive proteins, which change

their chemical structures when exposed to light.

Let me introduce you a protein which plays a significant role in

Optogenetics, the Channelrhodopsin

It is a channel protein which opens to ion transportation when exposed

to blue light

So now we are using this kind of proteins to control biological process.

Let’s have a case study. Mammals’ brains are

made of neurons, or also called nerve cells.

They send electrical pulses to control the body

or when the organism is thinking.

We insert these light-sensitive proteins into the

brain of a mouse. And when light hits the

channel rhodopsin gene, the excited nerve cell

carries out ion transportation and sends out

electrical pulses, which in turn affects the

behaviour of the mouse.

First of all, doctors are required to drill holes in people’s skulls to

carry out the surgery. It also involves changing the DNA of brain cells

unreliable and unpredictable, risky

optogenetics become more unfavorable.

Fiber optics could pose the threat of

infection and being uncomfortable and

having to carry heavy batteries

Optogenetics requires high tech work

and specific knowledge to let the whole

thing work.

extremely expensive

+ May reserved for the wealthy ones but

not ordinary people

+ Only a small number of people in the

society will be able to enjoy this new technology, optogenetics is not the

significantly great if it is not able to benefit the whole society.

Moreover, to let optogenetics to become efficient, specific knowledge

about the illnesses’ neural underpinning is needed. Unfortunately, this

kind of specific knowledge is one of the most important missing puzzle

pieces to let us solve major mental illness like depression.

Therefore, we can conclude that without the knowledge about the

illnesses’ neural underpinning, we cannot use this new technique. There

are still quite a number of unsolved question in this field too.

Cell culture, Network analysis

The optogenetic method provides new opportunities to analyze neural

networks. This can be achieved by growing cultured nerve cells on micro

or nano patterned substrates. Cells can be stimulated or silenced simply

by a light-beam with up to now unknown spatial precision. Only for

registration of the light evoked signals electrodes devices are necessary.

Results from these experiments are expected to be used for theoretical

work on neural nets.

Mapping of the brain and behavior

Immediately after having demonstrated that ChR2 can be used for

remote control of neurons, many laboratories started projects for the

mapping of the brain in living animals. Excellent work by various groups

shows, that the application of the optogenetic methods opens the door

in the near future for more detailed studies, which have not been

possible with the traditional electrical and optical methods. To name

some examples; studies are possible on which certain areas of the brain

are stimulated via light pipes. Results are obtained on the movement of

whisker of rodents; on the olfactory system where light replaces the

ligands, and on the movement of animals after stimulation of the motor

cortex.

Gene therapy

In the future gene therapy with the optogenetic tools appears possible.

Transduction via Adeno Associated Viruses (AAV) has been performed

successfully on the human eye to cure Lebers Congenital Amaurosis, by

transduction of cells in the human retina to replace the missing retinal

isomerase. In analogy to this, AAV´s could be loaded with the microbial

rhodopsins and could be used for gene therapy on the diseases listed

below.

What’s so good about optogenetics?

Recovery of vision

Experiments on photoreceptor deficient mice have shown that light

evokes potentials in the visual cortex after the transduction of the ON

bipolar cells with ChR2 in the retina. This indicates that the retina of the

animals regained photosensitivity, which is transmitted via the optic

nerve to the brain. Trajectories of the movement of the animals in the

dark and in the light show clearly an increased activity in the light as it is

obtained for wild type animals. It is conceivable that such an approach

might be possible for blind humans, suffering e.g. the dry or the

wet maculardegeneration. However, in order to come to this point many

biomedical, biophysical and technical hurdles have to be surmounted.

This would be an alternative to the technology, which implants

photosensitive chips in the human eye, which is far away from a

satisfying treatment.

Parkinson disease, Epilepsy

Besides the application of drugs Parkinson disease (PD) can be treated

by Deep Brain Stimulation (DBS). The method consists of the stereotactic

application of a metallic bipolar or quadrupole electrode to the nucleus

subthalamicus within the brain. With help of the electrodes an

oscillating electric field is applied stimulating the neuronal cells. With

this approach spectacular results are obtained, which represent a

substantial improvement compared to the drug therapy. Because of the

geometry of the electrodes a precision of about one millimeter can be

achieved. The extracellular stimulation by the electrodes induces not

only the required depolarization of cells, but also partially a

hyperpolarization, which inactivates cells with unwanted side effects.

This means that parts of the target area are not under perfect control.

The optogenetic method is completely different. If successful this

approach will lead to an improved treatment of PD: Virus induced

transduction of cells with ChR2 allows the activation of the target

structure in the brain via appropriate light sources without the side

effects. As discussed above the advantages are the cell specificity, high

temporal and spatial resolution in the micrometer range, which would

open ways for the stimulation of substructures of the nucleus

subthalamicus. The latter would give the chance to get a deeper

understanding of the cause of this disease.

With respect to Epilepsy similar arguments would hold, because here

certain areas in the cortex are affected. One could speculate that

optogenetics would attract focus also to other diseases including

neuropsychiatric diseases.

To summarize, optogenetics offers great opportunities to for basic

research in the neurosciences, as already has been demonstrated by

many laboratories worldwide. The biomedical applications, however,

hold unpredictable challenges and risks.

Stay tuned for more bio club’s

activities!!!!

Crosswords!!

E Q M E M R S I N Y B V B X U

E T A G E K G S S K S F I R D

C H L B U L C E H T N I O J U

N G S I J Z S G N B X N L S F

E I R W Y V N M R E E W O L I

I L M V C I R R C R L B G L Y

C E K P K O O U V X B G Y E A

S K Q A F E S E E H C S Y C L

O B M S C I T E N E G O T P O

R B N F M W N K C P K P U A H

U Y I G P S Y G E V S U E G N

E R S C L B W S B V O A F N C

N L Z M S C H O W A N L J A B

U B X R J K M H N E S S V R W

A G D M N E T S K G G M J T W

OPTOGENETICS, BIOLOGY, NERVE, CELLS,

NEUROSCIENCE, LIGHT, MSCHOW, MSLEE, MRSIN,

MRSLAM, MSWONG, MSLAU, CHEESE, MAKING,

JOINTHECLUB, GENE

,

Further reading:

http://www.youtube.com/watch?v=I64X7vHSHOE

http://faculty.washington.edu/chudler/opto.html

http://www.optogenetics.co.uk/index.html

http://www.united-academics.org/magazine/mind-brain/new-mri-techniques-what-i

s-brain-mapping-and-how-does-it-work-optogenetics-mit/

BIOLOGY CLUB BULLETIN TEAM: 5A (6) Anson Lam

4I (7) Justin Leung

3B (21) Shum Wing Zi

3F (27) Wu Jenny

4B (7) Mak Siu Hin

4B (13) Chan Cheuk Ki