Thursday, August 13, 2015

How do they cut genes?

The movie begins in a molecular biology laboratory. Among the test tubes containing several colored liquids you see Dr. Nekhorvich, a decent looking old man with his spectacles trying to hide the apparent fright in his eyes. As he gets himself ready to inject a red liquid into his veins, you hear on the backdrop:
"Every search for a hero must begin with something which every hero requires, a villain."
There have been some mingling with the DNA of what is in the red liquid. They called it 'Chimera', the villain. It is a virus which when administered to a person will kill him unless he is given with an antidote within the next 20 hours. Make a story around it and bring Tom Cruise.
BOOM! Mission Impossible 2 is a hit!

Genetic engineering has been the love of many science fiction directors and writers since the last two decades or so. Another example of a much recent movie is Jurassic World wherein the Indominus rex was a dinosaur made by getting genes from several early dinosaurs and some modern day animals. Then there's The Island, The Matrix series and many more films which circle around the stuff scientists do with DNA. I wonder why biologists in movies are displayed as preoccupied vicious creatures who are intelligent enough to develop these exquisite species but then are dumb enough too to let their creations destroy the world! Never mind, let's get to the point.

Ever wondered how these scientists make chimeras {organisms with new (recombinant) DNA}?
Interesting, isn't it? Making super species for our own good by some interchanging and placing of DNA! Moreover, this idea is something beyond robots. People have been thinking of inculcating feelings to a network of Integrated Circuits, but through genetic engineering one creates a fully developed organism who doesn't need battery recharging and where pondering over forming feelings is something pretty secondary! And the best part is that though such 'çhimeras' are not being developed right now but the basic technique to do such weird stuff has been introduced and is in full swing of development. So, we don't usually see genetically modified humans around us, however, there's a potential in this technique to make this very thought a reality. It's called the Recombinant DNA Technology (RDT) wherein DNA from at least two different organisms are combined to form a new recombined DNA. It's awfully intriguing how the genius minds of geneticists and molecular biologists found a way to cut out genes from an organism and recombine it with genes obtained form others and put it into hosts which would express the genes perfectly.
Here I'll be writing one of the aspects of the whole process - how do they cut genes?
We have scissors for papers, knifes for vegetables, drillers for land but what we need to cut is DNA and no doubt DNA is a biomolecule which would need another 'biological substance' to cut it. Now when biologists 'need' something for a purpose they don't simply make it like the other engineers do because of the complexities rendered by a biological system. Instead, biologists search for something somewhere in the nature that's already doing the job needed. So what our scientists wanted here was a substance, already existing in nature, that could cut DNA.
Voila! It turns out that the DNA cutting process was already happening inside bacteria by small proteinacious substances called the  "RESTRICTION ENZYMES" of the Restriction Modification System.
The Restriction modification system is like an immune system in bacteria.  Whenever a bacteria is infected by a virus, the virus leaves its DNA into the bacteria. Now for the bacteria, the viral DNA is something to be afraid of! To save itself from the viral DNA the restriction enzymes of bacteria comes to the rescue. These enzymes cut the viral DNA thus making it ineffective. Eventually, our bacteria stays healthy! These restriction enzymes were extracted out and used as a DNA cutting tool by biologists. There are special DNA sequences that different restriction enzymes cleave (eg: EcoR1 cleaves GAATTC) which enabled our scientists to cut DNA as per their requirements.
So there you are! If nature's got problems, the solutions to those are hidden among the peculiar systems of nature itself. You just need to find it out!
Enzyme named HindII was first extracted  in 1970 from the bacterium Haemophilus influenzae strain Rd. More than 900 such enzymes from 230 different bacteria have been isolated till date.

Now some of you 'genius brains' might be thinking - If restriction enzymes cleave DNA then why doesn't the bacterial restriction enzymes cut its own DNA?
Bacterium's not a dumb thing, you know! It modifies its own DNA, thus making it unrecognizable by its own restriction enzymes. Eg: methylation of adenine residues by EcoR1 methylase. ( It's perfectly fine if you didn't get the example in your head if you are not into biology. But in case you are a biology student, it's not!). So the modified bacterial DNA won't be cleaved by the enzymes and the bacteria will live on.
That's how the restriction modification system in bacteria works.

So now you know how restriction enzymes became the major tool to cut DNA for genetic engineers performing RDT (Recombinant DNA Technology). Sure, RDT has not been developed to make designer babies or superhumans but we are surrounded by fruits and vegetables obtained from genetically modified plants. Mutants of microbes are being selected as well as genetically modified for higher production of industrial potent goods.
Imagine the time when computer coding has just been introduced and the software engineers are lauding about their potential to develop Macs and Microsofts (Operating Systems). The engineers are however denied to do the same by the conservationists for it would produce generations of humans who'd be entirely depending on the systems. Though there's a tremendous scope of doing wonderful and revolutionary stuff with the OS as the engineers believe, but conservationists are afraid of its wrong usage and the fact that common man would just then stare at his phone all day and stop connecting with nature!
Today's genetic engineers are the software engineers of the time you just imagined. The only difference lies in the higher profoundness of not accepting the new in the conservationist's mind.         

Monday, March 16, 2015

Endosymbiotic theory

Imagine you swallow a fish and start breathing under water!
You feast on a bear and become a world champion in wrestling or you gulp down a cheetah and voila, now you're way faster than Usain Bolt!
Impossible, right?
Pretty true for the multicellular setting but guess what, your cells, each and every one of it has already had the nerve to do such bewildering stuff. Besides, had they not shown such prodigious conduct, our existence would have been a sure impossibility.

To explain how our cells did this magic, we'd have to know some high school basics first. 'Some" would actually be more, just familiarize yourself with PROKARYOTES and EUKARYOTES.
In the simplest of the languages, PROKARYOTES are the primitive cells devoid of organelles (membrane bound structures or simply, organs of a cell). Say, a human without organs.
EUKARYOTES are the more modern type of cells having organelles. Note that our cells, that is human cells along with plant cells are eukaryotes. So the question goes down to "Whence did the eukaryotic cells come?" The answer is given by Endosymbiotic theory.

( Don't get too edgy on reading this name 'Endosymbiotic theory'. Science can go queer at times. I still remember the day when I first read the word reciprocal. In no time both the number and my mood turned the other way round! Read on! It's brilliant.) 

The endosymbiotic theory tells us how prokaryotic cells absorbed other prokaryotic cells (endocytosis) and apparently didn't digest them but decided to stay together (symbiosis) and thus form a cell (or a supercell) which could perform both the functions of the previously independently existing cells. Thus they evolved and followed the "survival of the fittest ideology".
( I hope that wasn't a pretty long sentence to understand. That's the simplest way I could incorporate all the important points)

Now for the word called ELABORATING.....

Okay, so let's get back to the 'no AD no BC, far more hell back era' earth. Only 3 kinds of cells existed back then, say Chintu, Bittu and Tinku ( no Tom Dick and Harry. Indian names are far more cooler and ..... well ....funnier!)
# Chintu had the ability to wrap its cell membrane around things at it's proximity and eventually absorb them.
# Bittu could use light energy to produce sugars. ( Yes, you genius! Bittu could perform photosynthesis!)
# Tinku could break down sugars and release energy.
So Chintu, Bittu and Tinku were living independently and peacefully in their village. They loved each other and things were going pretty fine. But every story has a good old villan and here it's the environment. Soon, three of them realized that with time, their environment was getting stronger and if things would go on like they were, they'd probably die pretty soon.
 "We can't become what we need to be by remaining what we are"
So they quickly took the above piece of advice and decided to do something about the problem. No superhero could come and help them so the only option left was to become one. So one fine day, Chintu, in order to survive, absorbed Bittu but couldn't digest him. Now Bittu was no less smart. He started to divide while living inside Chintu. So now we had a supercell (saktiman) which could still absorb other cells and moreover could perform photosynthesis.
Similarly, a supercell (Krish) which could break down sugars as an additional function was formed.
Then there were supercells which could perform photosynthesis and break down sugars as well. So cool! (Rajnikant)
These Saktimans, Krish and Rajnikants were nothing but eukaryotic cells - every cell in your body and each cell in your brain which is making you read this blog (more precisely The Krish)

HOW COOL IS THAT?

So that's how your cells managed to swallow other cells, evolve in over some million years, made you, and now is making you read how it did such a great bloody job!
YOU....yes YOU miss/mister should be PROUD!
Getting back to where I started - you 'absorbing' a bear or supposedly a horse and managing to co-exist with it, or you gulping a whole cheetah and expecting a symbiotic relationship, or you swallowing a range of different species and ending up whispering *my precious*? - let's just keep that to our very own Potters and the Lords of mighty rings!

Now for the more biologically oriented readers.
 Energy producing cell was engulfed and thus formed the mitochondria while photosynthetic cells formed chloroplasts.
There are basically 3 evidences to prove this theory:
1. If we destroy chloroplasts and mitochondria of a cell, new ones won't be formed. So that means cells can't produce them.
2. Chloroplasts and mitochondria have their own DNA and ribosomes. Both the DNA and ribosomes are similar to bacterial DNA and ribosomes.
3. Chloroplasts and Mitochondria are double membrane structures where their outer membrane resembles the eukaryotic membranes and the inner ones represents the bacterial membranes, thus giving the evidence of endocytosis.

"It is not the strongest of the species that survive, nor the most intelligent, but the one most responsive to change" - Charles Darwin.