Behavior is a tricky thing…one's behavior thoroughly depends on: the time, the place where you are, the people with whom you are, your previous interactions with them, your state of mind, your what not…basically; sometimes it depend on all of these and sometimes just on one of them.
One’s behavior is adorned with various shades…and even a very brief interaction with a person gives us an insight into his/her behavior, basically you are in a position to imply or be conclusive about the person’s behavior.
But then why is it that we find or at least I (do) find it difficult to comment on rather be sure of my own behavior or how I behave in general with people.
Basically why is self analysis, so difficult???
Generally what we seem to do is start building our own frame, based on the views that others put forward about us or start looking towards ourselves from others shoes!
This I think is really difficult task…what makes it difficult is precisely our unwillingness to accept our short comings rather we are unable to take care of our own biases about ourselves.
More than that even if you know, about certain shades of your own behavior, its practically impossible to be quantitative.
But it was just yesterday that I came to know that I was addicted to the internet by 35%(after answering to a questionnaire on facebook) Many such questionnaires are available on the world wide web and they are quantitative too and by answering those many like you and me are doing the complex task of self-analysis or rather getting an insight into our own behaviors. At this point we might think that we do it just for fun and nothing like “self analysis” is even closely related to this, is it really???
Before even worrying about the scores assigned to each questions and how exactly the quantitation is done, I think there is a great flaw right in the beginning of the process.
That is, for any human surveillance that you carry out, it is necessary that the subject is unaware of your motives behind the survey.
And this condition is no way met during the exercise, cause you choose to answer the questionnaire, in the first place, because you are interested in particular behavior or character of yours. And it’s always that you have some pre-assumptions about yourself on those grounds and you successfully introduce a bias…! Also one’s you know the purpose of the whole process, from the options available you can easily predict the options that will give you scores at the two extremes and at the mean. The whole process along with its purpose fails, and I think it fails miserably!
In spite of this we enjoy taking the weirdest and stupidest of the quizzes on the www and waste our time, even when there are assignments, submissions and sometimes even exams!!!
So, which is the quiz you are taking up next???
Monday, April 20, 2009
Saturday, February 28, 2009
..... , ,,,,, ;: ::::: !
All the atoms and molecules around
Have been here for times unbound…
Something or the other kept them busy
Cause surviving here wasn’t easy…!
Every challenge faced was different from other
But there was no reason for them to bother…
Few of them always managed to find the key
To sail through the selection spree…
All of this was obviously at a high cost
Every time a majority of population was lost!
It was indeed a blessing in disguise
It assured the progeny the key choice…
It assured us a way to account the very selections
It assured us this through stable genetic mutations..!
Something so simple so reasonable so logical
Is unacceptable to some creationists classical…
Intelligent design is what they propagate
With ideas, data and views surrogate…!
Accept it or else forget but Evolution is the only explanation…
To the most complex and also to the simplest title of this poetic creation.,;:!
Have been here for times unbound…
Something or the other kept them busy
Cause surviving here wasn’t easy…!
Every challenge faced was different from other
But there was no reason for them to bother…
Few of them always managed to find the key
To sail through the selection spree…
All of this was obviously at a high cost
Every time a majority of population was lost!
It was indeed a blessing in disguise
It assured the progeny the key choice…
It assured us a way to account the very selections
It assured us this through stable genetic mutations..!
Something so simple so reasonable so logical
Is unacceptable to some creationists classical…
Intelligent design is what they propagate
With ideas, data and views surrogate…!
Accept it or else forget but Evolution is the only explanation…
To the most complex and also to the simplest title of this poetic creation.,;:!
Synthetic Biology: Engineer’s Approach to Biology
Abstract-
Contemporary biology recognizes the genes and proteins responsible for a particular cellular phenomenon, but today at this hour the focus is on deciphering the connectivity between those genes and proteins. Mathematical models best describes these circuits, which in reality resemble the electric circuits. In this scenario, biology is looked at through engineer’s perspective, providing the framework for the construction and analysis of the underlying sub modules that constitute the network. Thus synthetic biology creates a platform on which prediction and evaluation of dynamics of cellular processes is facilitated. In this review we will take a look at synthetic biology and the varied facets it offers.
Keywords: Synthetic biology, oscillator, reprissilator, cellular noise, biobricks.
“…the clock ticks life away…” teens hum on the tunes of Linkin park. (Popular band)
Though the lyrics refer to the passing time in context of digital clock or watch…the man created version. The same words hold true for the nature’s version of the clock…the biological clock as we may call it.
In order to understand how exactly the clock ticks or works…one may have to break open a clock and look at its components…best way to get a better insight into its working, is to try creating one’s own clock out of similar parts!
The previous is what contemporary biology deals with, using genetic and biochemical techniques to isolate genes and proteins involved in feedback loops of gene expression, that are necessary for clock functioning of biological clocks e.g. circadian rhythms.( Cyran, S. A. et al., 2003)
But the later, is the one which helps us answer insightful questions pertaining to the clock like-
1. What sets the period of the oscillation?
2. How does the clock operate reliably in diverse cellular conditions? and
3. What features of its design are responsible for its reliable operation?
The above mentioned i.e. creating a new clock; is the way Synthetic Biology approaches the biological dead ends! Several synthetic genetic clocks have now been constructed in bacteria and mammalian cell lines too.( Fung, E. et al, 2005; Tigges Marcel et al, 2009) These circuits are simpler versions of the actual naturally found biological clocks.
What exactly is synthetic biology?
Marc W. Kirschner (Department of Systems Biology Harvard Medical School) sheds light on it…
“Synthetic biology is the study of the behaviour of complex biological organization and processes in terms of the molecular constituents. It is built on molecular biology in its special concern for information transfer, on physiology for its special concern with adaptive states of the cell and organism, on developmental biology for the importance of defining a succession of physiological states in that process, and on evolutionary biology and ecology for the appreciation that all aspects of the organism are products of selection, a selection we rarely understand on a molecular level. Systems biology attempts all of this through quantitative measurement, modeling, reconstruction, and theory. Systems biology is not a branch of physics but differs from physics in that the primary task is to understand how biology generates variation. No such imperative to create variation exists in the physical world. It is a new principle that Darwin understood and upon which all of life hinges. That sounds different enough for me to justify a new field and a new name”
Synthetic biology deals with ‘programming’ of the cell. Reprogramming a cell involves the creation of synthetic biological components by adding, removing, or changing genes and proteins. Design, fabrication, integration, and testing of new
Cellular hardware lies at the core of this field. But the tools and methods necessary for same are derived from experimental biology. The process begins with the abstract design of devices, modules, or organisms, and is often guided by mathematical models. The synthetic biologist then tests the newly constructed systems experimentally. However, such initial attempts rarely yield fully functional implementations because of incomplete biological information. Rational redesign
Based on mathematical models comes for rescue in such situations.
Newer approaches to address and deal with synthetic constructs are also being developed-
1. One can just apply directed evolution to genes comprising a simple genetic circuit and what you get is evolution of improperly matched non-functional components to functional ones.( Yokobayashi Yohei et al, 2002)
2. In silico evolutionary procedure is also being used to create gene networks performing basic tasks. Main highlights of this procedure are that small functional modules with diverse functions can be created.( Franc¸ois Paul et al, 2004)
3. Yet another approach could be just to couple simple models into complex networks with behaviour that can be predicted from individual components. Thus properties of regulatory sub-systems can be used to predict behaviour of larger more complex regulatory networks.( Guido Nicholas et al, 2006)
Designing constructs…
Modeling and construction of many and varied gene regulatory circuits are reported till date. Oscillators being the most popular, are constructed by coupling positive and negative feedback loops, such that the whole system oscillates or moves back and forth between the two steady states. Also lots of variations are also possible here, in terms of the components that make the whole system oscillate.
In case of E.coli itself it is possible to construct oscillatory circuit using IPTG, lacI protein and arabinose regulatory sites, together.( Stricker Jesse et al, 2008; M Rachael et al, 2002) Similar is the deal with reprissilator in which three transcriptional repressor systems build an oscillator, but the twist is that the period of oscillation is shorter than cell-division cycle, so the state of oscillator needs to be transmitted to the next generations. Thus such reprissilator make possible, design and construction of artificial genetic networks with new functional properties from generic components that naturally occur in other contexts.( Elowitz et al, 2000)
In the same E.coli one can also create oscillations by exploiting glycolytic flux i.e. construction of a metabolator! In this acetyl phosphate acts as a signalling metabolite and under its control the two metabolite pools interconvert.( Fung, E. et al, 2005)
Toggle switches are another kind of circuits tried and tested in E.coli which require only transient induction and hence can function as a cellular memory unit. This can very well be exploited in industries, since it permits high induction of recombinant proteins without the high cost of large quantities of inducer. (Gardner Timothy et al, 2000)
Establishment of communication between bacteria by constructing an artificial quorum sensor has not only enabled intraspecies but also intrespecies communication possible, leading to various behaviours and phenotypes. It facilitates achievement of co-operative transcriptional response.(Garcia-Ojalvo Jordi et al, 2004; Bulter Thomas et al, 2004)
Mammalian cells are also being used for construction of oscillators which give self-sustained, tunable autonomous and robust oscillations, thus opening new vistas for future gene and cell therapies.( Tigges Marcel et al, 2009)
The untold story…
Synthetic biology is not just messing around with the genome (as it may seem to be from the above text) to make useful constructs, basically its not tinkerer’s approach but engineers approach to a problem.
One can say that success of synthetic biology is essential to understand life…this is because in this whole process of modelling, construction and testing the understanding of the system itself is achieved in a better way. This holds true not only for the insight into working of the cell cycle (a mitotic oscillator is at work there) (Goldbeter Albert, 1991) but also in understanding of the sleep-wake cycle or the circadian rhythms.
It is only while working with the synthetic constructs a phenomenon of “noise” comes into light. Noise is the one which can actually collapse your circuit or rather may give your circuit an insignificant and non-functional look! Trying to reduce the noise level in one’s own construct(Orrell David et al, 2004) leads to design enhancement and also appreciation of the noise resistant constructs found in the nature built circuits!( Vilar, J. M et al, 2002)
Fascinating shades…
A giant leap of synthetic biology is to “write the genome” as Craig Venter puts it! As a step in this direction not only have they constructed synthetic whole genomes(Smith Hamilton et al, 2003) but also expanded the genetic code with a functional quadruplet codon.(Which can incorporate unnatural amino acids into proteins.)(Anderson Christopher et al, 2004)
In order to bring all these constructs and related research in laboratories around the world under a common umbrella standard protocols and registry of the constructed parts has been developed on the World Wide Web http://partsregistry.org/Main_Page. It actually involves efforts to develop “tool box” of standardized genetic parts with known performance characteristics—analogous to the transistors, capacitors, and resistors used in electronic circuits—from which bioengineers can build functional Devices and, someday, synthetic micro organisms. The registry is made up of components called “BioBricks,” short pieces of DNA that constitute or encode functional genetic elements. Examples of BioBricks are a “promoter” sequence that initiates the transcription of DNA into messenger RNA, a “terminator” sequence that halts RNA transcription, a “repressor” gene that encodes a protein that blocks the transcription of another gene, a ribosome-binding site that initiates protein synthesis, and a “reporter” gene that encodes a fluorescent protein. A BioBrick must have a genetic structure that enables it to send and receive standard biochemical signals and to be cut and pasted into a linear sequence of other BioBricks. Further, work on the lines of improvising the repository of biobricks and methods for their easier handling is being done, actively.( Peccoud Jean et al, 2008; Shetty Reshma et al, 2008) Also work on the lines of developing an organism with minimum essential genes(Glass John et al, 2005), so that the organism can be exploited efficiently for integrating the constructs, is in progress.
Excellent examples of intelligent use of the toolbox involves -
1. Engineering a metabolic pathway for the synthesis of artemisinic acid in yeast, which is the immediate precursor of the drug artemisinin( a natural product) that is highly effective in treating malaria, thus reducing the cost of the drug.( Ro Dae-Kyun et al, 2006)
2. Construction of a sensory synthetic kinase that allows a lawn of bacteria to function as a biological film, such that the projection of a pattern of light on to the bacteria produces a high-definition (about 100 megapixels per square inch), two-dimensional chemical image. Thus using spatial control of bacterial gene expression to 'print' complex biological materials, for example, to investigate signalling pathways through precise spatial and temporal control of their phosphorylation steps.( Levskaya Anselm et al, 2005)
It is crystal clear that the field of synthetic biology has the potential to bring about epochal changes in science and a few decades from now it may have a profound influence on the definition of life, itself!
Perhaps the most intriguing problem right now is to observe how the designed circuit operates in the context of a complete organism. There are no dotted lines inside the cell isolating circuits from one another. The ultimate test for this synthetic approach is to delete natural circuits and replace them with synthetic counterparts within organisms. This will lead to interference of the synthetic circuits with the rest of the cell. Obviously these circuits would be less functional than their natural counterparts. But at this stage one can learn more by putting together a simple, though inaccurate, pendulum Clock, than one can by disassembling the finest Swiss timepiece.
(these days i am going gaga... over synthetic biology...so after my paper ppt my review follows...again on synthetic biology! nothing like it if get to work in relation to the field...hopefully!)
Contemporary biology recognizes the genes and proteins responsible for a particular cellular phenomenon, but today at this hour the focus is on deciphering the connectivity between those genes and proteins. Mathematical models best describes these circuits, which in reality resemble the electric circuits. In this scenario, biology is looked at through engineer’s perspective, providing the framework for the construction and analysis of the underlying sub modules that constitute the network. Thus synthetic biology creates a platform on which prediction and evaluation of dynamics of cellular processes is facilitated. In this review we will take a look at synthetic biology and the varied facets it offers.
Keywords: Synthetic biology, oscillator, reprissilator, cellular noise, biobricks.
“…the clock ticks life away…” teens hum on the tunes of Linkin park. (Popular band)
Though the lyrics refer to the passing time in context of digital clock or watch…the man created version. The same words hold true for the nature’s version of the clock…the biological clock as we may call it.
In order to understand how exactly the clock ticks or works…one may have to break open a clock and look at its components…best way to get a better insight into its working, is to try creating one’s own clock out of similar parts!
The previous is what contemporary biology deals with, using genetic and biochemical techniques to isolate genes and proteins involved in feedback loops of gene expression, that are necessary for clock functioning of biological clocks e.g. circadian rhythms.( Cyran, S. A. et al., 2003)
But the later, is the one which helps us answer insightful questions pertaining to the clock like-
1. What sets the period of the oscillation?
2. How does the clock operate reliably in diverse cellular conditions? and
3. What features of its design are responsible for its reliable operation?
The above mentioned i.e. creating a new clock; is the way Synthetic Biology approaches the biological dead ends! Several synthetic genetic clocks have now been constructed in bacteria and mammalian cell lines too.( Fung, E. et al, 2005; Tigges Marcel et al, 2009) These circuits are simpler versions of the actual naturally found biological clocks.
What exactly is synthetic biology?
Marc W. Kirschner (Department of Systems Biology Harvard Medical School) sheds light on it…
“Synthetic biology is the study of the behaviour of complex biological organization and processes in terms of the molecular constituents. It is built on molecular biology in its special concern for information transfer, on physiology for its special concern with adaptive states of the cell and organism, on developmental biology for the importance of defining a succession of physiological states in that process, and on evolutionary biology and ecology for the appreciation that all aspects of the organism are products of selection, a selection we rarely understand on a molecular level. Systems biology attempts all of this through quantitative measurement, modeling, reconstruction, and theory. Systems biology is not a branch of physics but differs from physics in that the primary task is to understand how biology generates variation. No such imperative to create variation exists in the physical world. It is a new principle that Darwin understood and upon which all of life hinges. That sounds different enough for me to justify a new field and a new name”
Synthetic biology deals with ‘programming’ of the cell. Reprogramming a cell involves the creation of synthetic biological components by adding, removing, or changing genes and proteins. Design, fabrication, integration, and testing of new
Cellular hardware lies at the core of this field. But the tools and methods necessary for same are derived from experimental biology. The process begins with the abstract design of devices, modules, or organisms, and is often guided by mathematical models. The synthetic biologist then tests the newly constructed systems experimentally. However, such initial attempts rarely yield fully functional implementations because of incomplete biological information. Rational redesign
Based on mathematical models comes for rescue in such situations.
Newer approaches to address and deal with synthetic constructs are also being developed-
1. One can just apply directed evolution to genes comprising a simple genetic circuit and what you get is evolution of improperly matched non-functional components to functional ones.( Yokobayashi Yohei et al, 2002)
2. In silico evolutionary procedure is also being used to create gene networks performing basic tasks. Main highlights of this procedure are that small functional modules with diverse functions can be created.( Franc¸ois Paul et al, 2004)
3. Yet another approach could be just to couple simple models into complex networks with behaviour that can be predicted from individual components. Thus properties of regulatory sub-systems can be used to predict behaviour of larger more complex regulatory networks.( Guido Nicholas et al, 2006)
Designing constructs…
Modeling and construction of many and varied gene regulatory circuits are reported till date. Oscillators being the most popular, are constructed by coupling positive and negative feedback loops, such that the whole system oscillates or moves back and forth between the two steady states. Also lots of variations are also possible here, in terms of the components that make the whole system oscillate.
In case of E.coli itself it is possible to construct oscillatory circuit using IPTG, lacI protein and arabinose regulatory sites, together.( Stricker Jesse et al, 2008; M Rachael et al, 2002) Similar is the deal with reprissilator in which three transcriptional repressor systems build an oscillator, but the twist is that the period of oscillation is shorter than cell-division cycle, so the state of oscillator needs to be transmitted to the next generations. Thus such reprissilator make possible, design and construction of artificial genetic networks with new functional properties from generic components that naturally occur in other contexts.( Elowitz et al, 2000)
In the same E.coli one can also create oscillations by exploiting glycolytic flux i.e. construction of a metabolator! In this acetyl phosphate acts as a signalling metabolite and under its control the two metabolite pools interconvert.( Fung, E. et al, 2005)
Toggle switches are another kind of circuits tried and tested in E.coli which require only transient induction and hence can function as a cellular memory unit. This can very well be exploited in industries, since it permits high induction of recombinant proteins without the high cost of large quantities of inducer. (Gardner Timothy et al, 2000)
Establishment of communication between bacteria by constructing an artificial quorum sensor has not only enabled intraspecies but also intrespecies communication possible, leading to various behaviours and phenotypes. It facilitates achievement of co-operative transcriptional response.(Garcia-Ojalvo Jordi et al, 2004; Bulter Thomas et al, 2004)
Mammalian cells are also being used for construction of oscillators which give self-sustained, tunable autonomous and robust oscillations, thus opening new vistas for future gene and cell therapies.( Tigges Marcel et al, 2009)
The untold story…
Synthetic biology is not just messing around with the genome (as it may seem to be from the above text) to make useful constructs, basically its not tinkerer’s approach but engineers approach to a problem.
One can say that success of synthetic biology is essential to understand life…this is because in this whole process of modelling, construction and testing the understanding of the system itself is achieved in a better way. This holds true not only for the insight into working of the cell cycle (a mitotic oscillator is at work there) (Goldbeter Albert, 1991) but also in understanding of the sleep-wake cycle or the circadian rhythms.
It is only while working with the synthetic constructs a phenomenon of “noise” comes into light. Noise is the one which can actually collapse your circuit or rather may give your circuit an insignificant and non-functional look! Trying to reduce the noise level in one’s own construct(Orrell David et al, 2004) leads to design enhancement and also appreciation of the noise resistant constructs found in the nature built circuits!( Vilar, J. M et al, 2002)
Fascinating shades…
A giant leap of synthetic biology is to “write the genome” as Craig Venter puts it! As a step in this direction not only have they constructed synthetic whole genomes(Smith Hamilton et al, 2003) but also expanded the genetic code with a functional quadruplet codon.(Which can incorporate unnatural amino acids into proteins.)(Anderson Christopher et al, 2004)
In order to bring all these constructs and related research in laboratories around the world under a common umbrella standard protocols and registry of the constructed parts has been developed on the World Wide Web http://partsregistry.org/Main_Page. It actually involves efforts to develop “tool box” of standardized genetic parts with known performance characteristics—analogous to the transistors, capacitors, and resistors used in electronic circuits—from which bioengineers can build functional Devices and, someday, synthetic micro organisms. The registry is made up of components called “BioBricks,” short pieces of DNA that constitute or encode functional genetic elements. Examples of BioBricks are a “promoter” sequence that initiates the transcription of DNA into messenger RNA, a “terminator” sequence that halts RNA transcription, a “repressor” gene that encodes a protein that blocks the transcription of another gene, a ribosome-binding site that initiates protein synthesis, and a “reporter” gene that encodes a fluorescent protein. A BioBrick must have a genetic structure that enables it to send and receive standard biochemical signals and to be cut and pasted into a linear sequence of other BioBricks. Further, work on the lines of improvising the repository of biobricks and methods for their easier handling is being done, actively.( Peccoud Jean et al, 2008; Shetty Reshma et al, 2008) Also work on the lines of developing an organism with minimum essential genes(Glass John et al, 2005), so that the organism can be exploited efficiently for integrating the constructs, is in progress.
Excellent examples of intelligent use of the toolbox involves -
1. Engineering a metabolic pathway for the synthesis of artemisinic acid in yeast, which is the immediate precursor of the drug artemisinin( a natural product) that is highly effective in treating malaria, thus reducing the cost of the drug.( Ro Dae-Kyun et al, 2006)
2. Construction of a sensory synthetic kinase that allows a lawn of bacteria to function as a biological film, such that the projection of a pattern of light on to the bacteria produces a high-definition (about 100 megapixels per square inch), two-dimensional chemical image. Thus using spatial control of bacterial gene expression to 'print' complex biological materials, for example, to investigate signalling pathways through precise spatial and temporal control of their phosphorylation steps.( Levskaya Anselm et al, 2005)
It is crystal clear that the field of synthetic biology has the potential to bring about epochal changes in science and a few decades from now it may have a profound influence on the definition of life, itself!
Perhaps the most intriguing problem right now is to observe how the designed circuit operates in the context of a complete organism. There are no dotted lines inside the cell isolating circuits from one another. The ultimate test for this synthetic approach is to delete natural circuits and replace them with synthetic counterparts within organisms. This will lead to interference of the synthetic circuits with the rest of the cell. Obviously these circuits would be less functional than their natural counterparts. But at this stage one can learn more by putting together a simple, though inaccurate, pendulum Clock, than one can by disassembling the finest Swiss timepiece.
(these days i am going gaga... over synthetic biology...so after my paper ppt my review follows...again on synthetic biology! nothing like it if get to work in relation to the field...hopefully!)
Wednesday, February 18, 2009
Abstract to paper ppt...scheduled 21st feb
yet another sem and yet another paper ppt....though my preparations ...hardly any preps...i m in love with synthetic bio these days...so here it is...abstract to my paper...no sorry abstract to the paper i selected...
A Tunable Synthetic Mammalian Oscillator
Marcel Tigges, Tatiana T. Marquez-Lago, Jo¨rg Stelling & Martin Fussenegger
Nature, Vol. 457,309-312 (15 January 2009)
Abstract
Oscillator circuits mediating the periodic induction of specific target genes are time-keeping devices found in circadian clocks. Here, is described the first controllable mammalian oscillator, constructed based on an auto-regulated sense–antisense transcription control circuit. The circuit encodes a positive and a time delayed negative feedback loop, enabling autonomous, self sustained and tunable oscillatory gene expression. The designed system was monitored using oscillating concentrations of green fluorescent protein with tunable frequency and amplitude, by time-lapse microscopy in real time in individual Chinese hamster ovary cells. This synthetic mammalian clock may provide insight into dynamics of natural periodic processes and also enable complex gene therapy treatments by automating physiological processes in future gene and cell therapies.
References-
1. Jesse Stricker, Scott Cookson (2008) A fast, robust and tunable synthetic gene oscillator. Nature, Vol. 456, 516-520
2. Crosthwaite, S. K. (2004) Circadian clocks and natural antisense RNA. FEBS Lett. 567, 49–54
3. Gossen, M. & Bujard, H. (1992) Tight control of gene expression in mammalian cells by tetracycline-responsive promoters. Proc. Natl Acad. Sci. USA 89, 5547–5551
A Tunable Synthetic Mammalian Oscillator
Marcel Tigges, Tatiana T. Marquez-Lago, Jo¨rg Stelling & Martin Fussenegger
Nature, Vol. 457,309-312 (15 January 2009)
Abstract
Oscillator circuits mediating the periodic induction of specific target genes are time-keeping devices found in circadian clocks. Here, is described the first controllable mammalian oscillator, constructed based on an auto-regulated sense–antisense transcription control circuit. The circuit encodes a positive and a time delayed negative feedback loop, enabling autonomous, self sustained and tunable oscillatory gene expression. The designed system was monitored using oscillating concentrations of green fluorescent protein with tunable frequency and amplitude, by time-lapse microscopy in real time in individual Chinese hamster ovary cells. This synthetic mammalian clock may provide insight into dynamics of natural periodic processes and also enable complex gene therapy treatments by automating physiological processes in future gene and cell therapies.
References-
1. Jesse Stricker, Scott Cookson (2008) A fast, robust and tunable synthetic gene oscillator. Nature, Vol. 456, 516-520
2. Crosthwaite, S. K. (2004) Circadian clocks and natural antisense RNA. FEBS Lett. 567, 49–54
3. Gossen, M. & Bujard, H. (1992) Tight control of gene expression in mammalian cells by tetracycline-responsive promoters. Proc. Natl Acad. Sci. USA 89, 5547–5551
Saturday, January 24, 2009
Countryside experience…
In the school days …specially during summer vac, everyone all my frnds used to go to their native places…a concept of going to ur “gaon” Same was true for me…even I enjoyed going to my “gaon”…but fortunately or unfortunately for me…this “gaon” was nagpur or bandra or virar it wasn’t a typical Indian gaon ever….a complete misnomer in my case! Never in my life had experienced a typical Indian village. Had only heard about it from friends and foes.
Until the 17th jan 2009.
We stayed at a place called Revsa a beautiful village in Amravati district in Vidharba region of Maharashtra.
Before going to this place Revsa we first visited Aarvi.
Day1
Aarvi is a place where apparently many maharaj’s or saints supposedly “prakat huae hain”
Vidharba region being much of a plateau….through out our journey my eyes were constantly searching for a site of a tall mountain blocking the horizon, a site common back here. Btw the Horizon was just perfect…adorned with orange or tur dal fields abundantly found there. Instead of green ….most of the vegetation there was golden….and this shade also looked amazing!!
Also there was this road which completely resembled that extra milage ad wala road which fits between your thumb and index finger!
Frankly speaking the road was quite lonely…no petrol pumps no food malls but a single 15rs toll which was previously 2rs!!!
There at Aarvi particular incidence happened worth a mention:
Our car had taken a wrong side on a two way well divided road…and quite spontaneously I brought that to the drivers notice….only to make a fool of my self…as he explained that the other side of the road is meant for hawkers per se and it is right to drive from wrong side of the road!!!
Also got a chance to pull a bucket of water outside the well, near the temple…managed to spill half of the water till the bucket reached the top…funniest part was…my cousin managed to take a pic of this act and it looked like someone trying to pull me inside the well…tug of war kinda situation.
Way back from Aarvi…read a board “char dhokadayak valne…savdhan!” I was wondering what on this planet made them construct such a road on a plain surface!
For what???
So that drivers don’t speed up???? Our driver I don’t think so crossed 60 on a scarcely populated road…with hardly any disturbances.
May be due to the fields alongside the road, may be, though doubtful about this one!
.
Anyways, from Aarvi we headed to Revsa…place of our stay for coming 3 days…
We headed towards the Samadhi place…which was just soothing …a pretty isolated place from even the Revsa village, it was in fact just outside the village. While returning home…we wandered through the heaps of crops kept for processing…got onto a still cart and posed for weird pics! Enjoyed the act to the core…!
Just enjoyed the bullock cart ride back home…it was like hiring a rick back here…minus the attitude minus the debate for the right fare minus the sound of the honking horns…it was rocking! (Literally)
The setting sun made the ride just perfect!
Now back there in Revsa for the 4 days of Utsav, food is served for free to the ppl…and they don’t have appointed ppl to serve the food, so…whosoever is interested and wants to serve…goes right there..!
Let me tell you the job isn’t easy at all….I mean at the end of it. I was sweating like hell…my hands suffered a few heat shocks…and also something: Weird took place…
There I was serving the steam cooked rice and by mistake I served it at a wrong place….and spontaneously on realizing my mistake said sorry and the child there replied...”sorry mhanaje?” He actually did not even know the meaning of sorry!!! I stood confused? Embarrassed? Don’t know what that feeling was!
Quite recently I had actually started doubting the fact that the stars in the night sky are uncountable, coz had hardly seen any stars back here in the sky…!
But the night out there in revsa, with millions of stars in the sky… was just amazing!
Just kept like starring at the sky till the dawn…!
Day2
The morning sunrise was another beautiful sight exclusive to the village.
All the evenly dung clad houses were adorned with beautiful rangolis at there doorsteps.
All the cattle's were leaving their gotha for grazing…btw every house out there had a gotha of the same size that of the house or even larger.
The morning tea from the very fresh pure unadulterated milk was hmmm…
There was this pretty young calf who was innocently wandering around. Managed to capture an amazing video of her’s.
We all headed to place called “Ganoja” Another village of its kind…!
The river near the temple was mast…had lots of fun out there. In spite of the scorching sun on top, the flowing river water was cold. Here we came across quite a few different kinds of birds. Managed to click some beautiful pics here too….
The site of the cattle’s, horses, birds heading to the water body for quenching their thirst…the village ladies washing clothes…the act of crossing the river and moving to the other side …made the day most memorable.
Can’t forget to mention about the food that we had at “Ganoja”…I wont be exaggerating it was one of the world’s best food served! The Puranpoli couldn’t have ever tasted better…my taste buds enjoyed the food carnival that day…for sure!
Day 3 and 4
With no more visits to other places…we were right there to explore the village “Revsa” Frankly speaking one can finish exploring the village in less than 1hr...It’s that small. What fascinated me was, that most of the houses were “shenani saravlele” and that was so perfectly done that the walls of those houses looked smoother and better than once painted by the best quality Paint available.
Also in case of walls the arrangements of bricks looked strikingly different…i.e.the pattern of arranging bricks for constructing the wall was different!
There was this small house out there; this was the village “dakghar”
I just loved the houses out there in the village….don’t know what exactly clicked me the most…but I surely loved them!
On people…!
I guess this might be the only village without doodhwala…coz everyone has enough cattles to take care of their dairy products requirements!
By and large I found people to be helpful and hardworking.
Worth a mention is this guy called “bhaiyaji”…a muslim by religion but stays and works in the temple…this man is really hardworking and energetic...he never looks tired…is never bugged…does all the work that comes to him…the first one to get up and last one to sleep out there…we all actually doubted that he sleeps!
The people here are creative too…on the day the “palkhi” takes a tour of the village…the people in their locality arrange or make a “dekhava” There was this one particular dekhava in which there was this child dressed like hanuman and was made to lean on a wooden plank connected up in the air using cables and was made to head towards a source of light representing the sun…that was really good! (btw this act symbolized the (apparently)well known story of hanuman who one’s gets up hungry…and tries to eat the sun thinking that its some kind of a big fruit)
One of the other theme was unity in diversity!
There was this other dekhava…which made an excellent use of the small water holders in the village meant for cattle's…as a source of drinking water. Using a long rubber pipe they constructed a snake and made a child dress like Krishna and stand on it!
During the palkhi tour through the village, clad with dekhava at different locations …the route that the palki followed was decorated beautifully with rangolis, flowers, lighting and happiness and enthusiasm on people’s face!
On food…!
I have never in my post childhood ages drank so much of milk and ate so much of dahi ever!!!! The taste of fresh unadulterated milk and dahi made out of it…was just yummy…! Everyday we used to have minimum one and a half or two ltrs of dahi and 3-4 ltrs of milk for approx 10 -15 ppl and the distribution was definitely not equal …highly skewed at 3-4 ppl including me of course!!!
Even the vegetables brought by the bhajiwala…were so fresh and they definitely tasted and looked better than the vegetables we get out here! And they were definitely cheap…everything was around 5-6 Rs kg…! We hardly get 250gms for the same cost here and that to grown along the rails or some other shabby place using dirty water…!
Even enjoyed cooking…for the first time ever in my life!
On Gaon Jevan…!
On the final day is the “Gaon jevan” it’s a feast for all the villagers and people who come up to the village for the yatra. Literally thousands of people have lunch out there at the same time…and there’s just one pangat…!
This is were the management of the people was strikingly evident…with little place for confusion everyone is served with tons of tasty food that is cooked!
The food that is cooked for gaon jevan is tremendous… looking at the containers used to cook…stacks of chapattis made and rooms filled with food…you get the whole picture of the gaon jevan crystal clear!
All in all completely, thoroughly, dilse enjoyed my stay…my first visit of a kind…was full of fun, masti and quality time with my family…made me forget of all the tensions, backlogs and submissions back here…a perfect system reboot!
Until the 17th jan 2009.
We stayed at a place called Revsa a beautiful village in Amravati district in Vidharba region of Maharashtra.
Before going to this place Revsa we first visited Aarvi.
Day1
Aarvi is a place where apparently many maharaj’s or saints supposedly “prakat huae hain”
Vidharba region being much of a plateau….through out our journey my eyes were constantly searching for a site of a tall mountain blocking the horizon, a site common back here. Btw the Horizon was just perfect…adorned with orange or tur dal fields abundantly found there. Instead of green ….most of the vegetation there was golden….and this shade also looked amazing!!
Also there was this road which completely resembled that extra milage ad wala road which fits between your thumb and index finger!
Frankly speaking the road was quite lonely…no petrol pumps no food malls but a single 15rs toll which was previously 2rs!!!
There at Aarvi particular incidence happened worth a mention:
Our car had taken a wrong side on a two way well divided road…and quite spontaneously I brought that to the drivers notice….only to make a fool of my self…as he explained that the other side of the road is meant for hawkers per se and it is right to drive from wrong side of the road!!!
Also got a chance to pull a bucket of water outside the well, near the temple…managed to spill half of the water till the bucket reached the top…funniest part was…my cousin managed to take a pic of this act and it looked like someone trying to pull me inside the well…tug of war kinda situation.
Way back from Aarvi…read a board “char dhokadayak valne…savdhan!” I was wondering what on this planet made them construct such a road on a plain surface!
For what???
So that drivers don’t speed up???? Our driver I don’t think so crossed 60 on a scarcely populated road…with hardly any disturbances.
May be due to the fields alongside the road, may be, though doubtful about this one!
.
Anyways, from Aarvi we headed to Revsa…place of our stay for coming 3 days…
We headed towards the Samadhi place…which was just soothing …a pretty isolated place from even the Revsa village, it was in fact just outside the village. While returning home…we wandered through the heaps of crops kept for processing…got onto a still cart and posed for weird pics! Enjoyed the act to the core…!
Just enjoyed the bullock cart ride back home…it was like hiring a rick back here…minus the attitude minus the debate for the right fare minus the sound of the honking horns…it was rocking! (Literally)
The setting sun made the ride just perfect!
Now back there in Revsa for the 4 days of Utsav, food is served for free to the ppl…and they don’t have appointed ppl to serve the food, so…whosoever is interested and wants to serve…goes right there..!
Let me tell you the job isn’t easy at all….I mean at the end of it. I was sweating like hell…my hands suffered a few heat shocks…and also something: Weird took place…
There I was serving the steam cooked rice and by mistake I served it at a wrong place….and spontaneously on realizing my mistake said sorry and the child there replied...”sorry mhanaje?” He actually did not even know the meaning of sorry!!! I stood confused? Embarrassed? Don’t know what that feeling was!
Quite recently I had actually started doubting the fact that the stars in the night sky are uncountable, coz had hardly seen any stars back here in the sky…!
But the night out there in revsa, with millions of stars in the sky… was just amazing!
Just kept like starring at the sky till the dawn…!
Day2
The morning sunrise was another beautiful sight exclusive to the village.
All the evenly dung clad houses were adorned with beautiful rangolis at there doorsteps.
All the cattle's were leaving their gotha for grazing…btw every house out there had a gotha of the same size that of the house or even larger.
The morning tea from the very fresh pure unadulterated milk was hmmm…
There was this pretty young calf who was innocently wandering around. Managed to capture an amazing video of her’s.
We all headed to place called “Ganoja” Another village of its kind…!
The river near the temple was mast…had lots of fun out there. In spite of the scorching sun on top, the flowing river water was cold. Here we came across quite a few different kinds of birds. Managed to click some beautiful pics here too….
The site of the cattle’s, horses, birds heading to the water body for quenching their thirst…the village ladies washing clothes…the act of crossing the river and moving to the other side …made the day most memorable.
Can’t forget to mention about the food that we had at “Ganoja”…I wont be exaggerating it was one of the world’s best food served! The Puranpoli couldn’t have ever tasted better…my taste buds enjoyed the food carnival that day…for sure!
Day 3 and 4
With no more visits to other places…we were right there to explore the village “Revsa” Frankly speaking one can finish exploring the village in less than 1hr...It’s that small. What fascinated me was, that most of the houses were “shenani saravlele” and that was so perfectly done that the walls of those houses looked smoother and better than once painted by the best quality Paint available.
Also in case of walls the arrangements of bricks looked strikingly different…i.e.the pattern of arranging bricks for constructing the wall was different!
There was this small house out there; this was the village “dakghar”
I just loved the houses out there in the village….don’t know what exactly clicked me the most…but I surely loved them!
On people…!
I guess this might be the only village without doodhwala…coz everyone has enough cattles to take care of their dairy products requirements!
By and large I found people to be helpful and hardworking.
Worth a mention is this guy called “bhaiyaji”…a muslim by religion but stays and works in the temple…this man is really hardworking and energetic...he never looks tired…is never bugged…does all the work that comes to him…the first one to get up and last one to sleep out there…we all actually doubted that he sleeps!
The people here are creative too…on the day the “palkhi” takes a tour of the village…the people in their locality arrange or make a “dekhava” There was this one particular dekhava in which there was this child dressed like hanuman and was made to lean on a wooden plank connected up in the air using cables and was made to head towards a source of light representing the sun…that was really good! (btw this act symbolized the (apparently)well known story of hanuman who one’s gets up hungry…and tries to eat the sun thinking that its some kind of a big fruit)
One of the other theme was unity in diversity!
There was this other dekhava…which made an excellent use of the small water holders in the village meant for cattle's…as a source of drinking water. Using a long rubber pipe they constructed a snake and made a child dress like Krishna and stand on it!
During the palkhi tour through the village, clad with dekhava at different locations …the route that the palki followed was decorated beautifully with rangolis, flowers, lighting and happiness and enthusiasm on people’s face!
On food…!
I have never in my post childhood ages drank so much of milk and ate so much of dahi ever!!!! The taste of fresh unadulterated milk and dahi made out of it…was just yummy…! Everyday we used to have minimum one and a half or two ltrs of dahi and 3-4 ltrs of milk for approx 10 -15 ppl and the distribution was definitely not equal …highly skewed at 3-4 ppl including me of course!!!
Even the vegetables brought by the bhajiwala…were so fresh and they definitely tasted and looked better than the vegetables we get out here! And they were definitely cheap…everything was around 5-6 Rs kg…! We hardly get 250gms for the same cost here and that to grown along the rails or some other shabby place using dirty water…!
Even enjoyed cooking…for the first time ever in my life!
On Gaon Jevan…!
On the final day is the “Gaon jevan” it’s a feast for all the villagers and people who come up to the village for the yatra. Literally thousands of people have lunch out there at the same time…and there’s just one pangat…!
This is were the management of the people was strikingly evident…with little place for confusion everyone is served with tons of tasty food that is cooked!
The food that is cooked for gaon jevan is tremendous… looking at the containers used to cook…stacks of chapattis made and rooms filled with food…you get the whole picture of the gaon jevan crystal clear!
All in all completely, thoroughly, dilse enjoyed my stay…my first visit of a kind…was full of fun, masti and quality time with my family…made me forget of all the tensions, backlogs and submissions back here…a perfect system reboot!
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