Archive for June 2006

 
 

Tomatoes to contain vaccines for HIV and HBV

Now tomatoes can be put to even better use as researchers have planned to use tomatoes to deliver HIV and HBV vaccines. I would call that superbly innovative. They have genetically modified the tomato to contain fragments of HIV protein coat genes, so when these tomatoes are eaten, a person also takes up the protein coats of the viruses which can then serve as antibodies.

Click Here to read the story.

Constructive Biology by George Church in Edge Magazine

The Edge Magazine has released an issue dedicated to constructive biology. The article is very well written and gives a beautiful view of where we are headed as far as our *playing god* is concerned. Church clearly proves that he is an excellent scientific writer as he explains the present scenario of synthetic biology in layman’s language.

On the whole he discusses that as we are just beginning to manipulate biology with precision, people are getting excited. Newer technologies are enabling individual to do larger things and an individual can either do good or bad. This is demonstrated by the fact that today any person with a computer and decent enough programming skills is able to create a computer virus/worm which can cost billions of dollars to the world economy.

If we do the same in biology, we will give complete freedom to a single person to create whatever he wants. So, addressing security concerns should be of utmost priority for international community and government.

I also liked a few mind-bending sentences in the article such as:

Simulating a Living Thing on a Living Thing.”

We seem to be ‘designed’ by nature to be good designers.”

There is also a (short) response to this article by George Dyson. I replicate that response below:

Are we learning to manipulate life or is life learning to manipulate us?

A plausible scenario for how we arrived at life as we know it is that primitive organisms were infected by self-replicating parasites, learned to adopt those self-replicating processes, and became eukaryotic cells. Now, our still-primitive life-forms have again been invaded by self-replicating parasites (a network of code-consuming and code-spewing microprocessors) and life will, once again, adopt these self-replicating processes, on its own terms, for its own ends (with our help). Life (and evolution) as we know it will never be the same.”

This is quite possible, isn’t it?

Click here to read that article.

Quantum Mechanics and The Theory of Evolution

I had a wild thought yesterday. The Theory of Evolution can be analogous to the Theory of Quantum Mechanics. I know this might seem ridiculous, but I may try to explain it a little bit. See, the states of a particle (position, momentum, spin, etc.) may be compared with the genepool of a species (or all life). Given the current state of a particle, we can never precisely tell the future state of the same particle. This happens due to inherent randomness in quantum reality.

The same can said for the genepool also. Given the genepool at a particular time, you cannot predict the genepool in the future. This is because you cannot predict the course of evolution. There is inherent randomness in the evolutionary path.

Keeping these fundamental points in minds, we can compare this two (seemingly) unrelated fields. How about using Schrodinger’s equation for evolution? This would mean that each type of genepool has a probability value attached to it. Some genepools are more probable and some are less probable.

We may also use some of the principles of evolution such as Natural Selection for describing the quantum phenomena. Why is it that a few states of a particle are more probable than others? This may be due to the selection of those states by the environment. This means that environment which comprises of (competition from) other particles affects the state of the particle.

I think this analogy should be given more thought than I have given to it. The above argument may be scientifically wrong in many ways, but I hope I have conveyed the spirit which I wanted to.

Do you have GUTs in you?

Is the Grand Unified Theory really elusive? No, I don’t mean combining General Relativity with Quantum Mechanics. I mean some theory which thousand times more subtle and has equal importance as the grand unified theory of physics which would explain everything.

Here I talk about the theory of everything for biology. The theory which would account for each and everything we observe in biology and would explain the cause of experimental data obtained from biology experiments. The first question which pops into the mind is that: is a unified theory for biology even possible? Well, the term surely looks like an oxymoron and that is because biologists, traditionally, have relied hugely upon experimental data (and that is because it was far easier to obtain data and explain it than to make theories, hypothesis and then test the predictions). The end result of this data-driven madness was that biology is now so complex that even two biologists (working in not too-distant fields) are not able to comprehend fully what the other person is working on. The Science’s (or biology’s) ultimate aim is to make natural phenomena comprehensible to the man.

Now, look what has happened. Give a popular science (or biology) journal or even a magazine to a layman, and he won’t understand a word in it. Why? Was this the aim of biologists? Why can’t we compress whole of the biology into one equation and then let it unleash its power? The simplicity of the equation E=MC2 has made it the most famous equation world over. Why can’t we do in the biology what Einstein did to physics?

A majority of you would say that it hasn’t been done because it is not possible. I say, prove that it is not possible. I often wonder why it has not been tried yet. Or maybe I am ill informed about that. But the mere thought of biology not having a common framework is little terrifying. Today, what is needed is a mathematical framework from where we can start the quest for this theory.

I suspect ‘Evolution‘ could be one of the candidates for such theory. But, again, as I said we (biologists) are lacking a sound mathematical (or logical) basis upon which to base the theory. Once we agree on a common platform, then we can try developing evolution as THE ULTIMATE THEORY OF BIOLOGY.

I, myself, am hunting for one such idea which can cause paradigm shift in biological sciences. I imagine one day when biologists will prefer theory and mathematics more than the instruments and patience.

I don’t say that biologists are doing wrong when they do wet experiments. If it were, we would never have any vaccines, dolly sheep, Nature journal, etc. All I am saying that efforts should be devoted to make biology less complex and more compact. And the tool for that could only be mathematics.

The Origin of Life — Metabolism first or Genes first?

The evolutionary equivalent of chicken-and-egg problem is the origin of life. The question of how did life came into being is a great(est) topic for debate and research today. There are essentially two hypothesises regarding this: first one ( “RNA world” ) says that the first molecules to be alive were RNA molecules which have both catalytic and hereditary information carrying capacity. But it is being argued that it should be highly unlikely that RNA molecules of sufficient length could have been possible because the conditions then were quite harsh.

The second hypothesis, which is gaining support these days, is called “metabolism first”. It means that the metabolic reactions preceded the genetic information carriers. The reactions occurred in self-sustaining way, each one looping around to grow into bigger and bigger cycles. Occasionally these reactions would have split into two independent reactions. There may even be evolution in these reaction mixtures as the new compounds (which can better metabolize and generate energy faster) can replace the old compounds.

As for my personal opinion, I (as of now) believe in RNA world theory. I think I will take time to ponder on “metabolism first” model of origin of life. But, anyway, both the hypothesis are challenging and worthwhile to devote one’s time on researching.

Click Here to read latest on this topic.

Things I have learnt at IISc

Here, I will be listing the techniques I am learning at IISc, Bangalore

Wet Techniques
——————
1. Lysate Preparation
2. Transduction
3. Plating and Streaking
4. PCR
5. Inoculation
6. DNA Gel Electrophoresis
7. Beta-Galactosidase Assay
8. The Black Art of Making Cotton-Plugs :)
9. Plasmid DNA prep
10. Competition Assays
11. Competent Cells Synthesis :)
12. Transformation

Computational Techniques
——————————
1. Design of Biochemical Pathways and Genetic Circuits
2. Basics of SBML

Nanobacteria or self-replicating calcium crystals?

A few researchers have discovered a new form of life (as the claim!). These are the particles which are about 100 times smaller than a normal bacterium. These supposedly self-replicate and infect mammalian cells. The researchers have also found that the nanobacteria can cause kidney stones.

I don’t know how much of the report is believable of now, but you may Click here to read the news.

Virtual (Molecular) Biology Experiments

Here at IISc, I have realised that the molecular biology experiments (with E. coli) take a lot of time to occur. You prepare a strain, incubate it, run gels, etc. All of these things take time, and I am talking of a lot of time.

How nice would it be to have a software package to do all this in simulations and get the results instantaneously. It will allow to define the experiments in a script. Just run the script and lo! you have results in a flash. The scripts could be something like below:

#include STRAIN_1
#include STRAIN_2
#include Lamda_Phage

void main()
{

set a=TAKE(STRAIN_1, 5ml);
set b=TAKE(STRAIN_2, 5ml);
set c=TAKE(Lamda_Phage, 5ml)

incubate(a, 1litre, 12 hours);
incubate(b, 1litre, 2 hours);

set d=MIX(a,c);
set e=MIX(b,c);

for(i=1;i<10

gr_1[i]=WRITE("Optical Density of Strain_1 + Phage at "+ i +" hrs is: " + OD(d, i hrs); //Optical Density
gr_2[i]=WRITE("Optical Density of Strain_2 + Phage at "+ i +" hrs is: " + OD(e, i hrs);

}

PLOT(gr_1,gr_2, x-axis="Time (hrs)", y-axis="OD" );

}

Wouldn’t it be nice that you just design the experiments and they happen automatically? The software package (which I would call Biomation (Biology Automation)) would model accurate micro level and macro level behavior of many bacterial cells, eukaryotic cells and viruses. Indeed, the organisms can just be modules. The biomation should be complex enough to model evolution, molecular biology, crude physics, chemistry, etc.

We may even do experiments for observing taking up of aerobic bacteria by pre-eukaryote and then arise of mitochondria, performing recombinant DNA experiments, observing the cell communication, etc. In a nutshell, using a modular approach the biomation should facilitate every experiment imaginable.

The biomation could even kick-start the geek culture in biology as more people could write modules and share them online. They will share experiments using scripts. It will also facilitate widespread education in molecular biology as the kids and the places which cannot afford a full-blown lab will now can perform experiments on their computers.

It would be wonderful if we could reduce the biology experiments to merely a thought-process and thereby eliminating the time-consuming and error-prone physical experiments.

I wish I had time enough to write the biomation. But I seriously believe that the biomation should be a reality soon. And this is because it has potential to change science forever.

Bgl operon aka Cryptic Genes

I have started working on Bgl operon in E. coli at IISc, Bangalore. It is a type of cryptic genes, which means that there is no reason for a cell to maintain those genes in its genome. Bgl operon is normally in inactive state due to an indirect repeat ahead of promoter which prevents its recognition by RNA polymerase. It further has attenuation control mechanism.

The point is that the inverted repeats render the operon inactive hence it is unable to metabolise salicin (Bgl’s normal function). It is only due to mutation in inverted repeats which can activate the operon.

Now two questions come into the mind:
1. Since encountering of salicin is a very unlikely event, why is Bgl operon present in the genome in the first place.
2. Even if it is maintained, why is it in inactive state which renders it unable to utilize salicin. Only after the mutation (which is again unlikely) it is able to metabolize salicin if present in environment.

For explaining these questions, we have two hypothesises:
1. Bgl operon has some other function also (apart from normal metabolization of salicin)
2. Bgl is maintained because a cell can expect salicin in the environment in future. But it cannot afford to waste its cellular resources on an inducible operator because the probablity of encountering salicin is extremely low.

I intuitively believe in second hypothesis, but evidence suggests otherwise.

More on this later.

Reached IISc

I have reached IISc. I will be working in Prof. Mahadevan’s lab in Molecular Reproduction, Development and Genetics. The lab is nice with many equipment. I will probably be working on bgl operon in bacteria (cryptic genes).

The work seems to be interesting as the task would be to find why exactly the cryptic genes are not naturally in (genetically) ON state.

I am staying at IAS guest house which is 7 kms from IISc. The place is aloof, clean and well maintained. BTW, Bangalore city is very green and the people are very friendly.

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