Saturn is calling...

There is a great buzz on social media regarding the GRAND FINALE of the highly successful Cassini spacecraft before throwing it on Saturn, in turn destroying it. GRAND FINALE would include its movement very very close to Saturn's ring and that too for 22 times!! 

GRAND FINALE of CASSINI spacecraft includes
22 ring-grazing orbits. (Image:NASA)

It includes trips through 2000 km gap between first ring and the atmosphere of the planet. The spacecraft will move at an astounding speed of 1.2 lakh km/hr (77000 miles/hour) with respect to Saturn. Before its death, It will go where no other spacecraft has ever gone, right in between those rings and by this it will culminate years of dedicated effort by thousands of humans. But why to ' kill' a spacecraft which has improved our understanding of the solar system at a logarithmic scale? Which gave us thousands of images? Inspired us ? Why not leave it orbiting around the Saturn, like moon does around earth? 

It looks cruel to kill it but in reality its not. 

Huygens probe was dropped
by CASSINI on Titan.
(Image:NASA)

Before that we need to pause and comprehend the big picture here. 

The universe is mysterious. It has been the same for thousands of years, since the humans left their cradle of origin in Africa. Across cultures, present and past, we see reverence sometimes fear of the stars, moon, sun and planets. The unknown of the heavenly bodies have mesmerized us for centuries. Now as we move through the 21st century, we are beginning to get the glimpse of their secrets for the first time. The same curiosity which helped us get out of Africa, fuels our desire to explore other worlds. In the last few decades humans have sent huge numbers of space probe to study various planets comets and asteroids of our solar system. Over time tremendous amount of data has increased our knowledge of these worlds. Layering over these initial observations new mysteries continues to arise. Every time a new information pours in from these probes, it stirs the curiosity of even the most placid human. One such mission to explore Saturn and its moons is Cassini-Huygens. 

Lightning storm captured by CASSINI in the
Saturn's atmosphere. (Image:NASA)

The Cassini took 7 years to reach Saturn and that too using gravitational assistance of Venus, Earth and Jupiter. Saturn remains no longer the planet with its rings to adore. Its appreciation goes deep with the Cassini's observations of the lightening storms on Saturn, shining brilliant aurora and its hexagon clouds at the poles. There seem to be no end to fascinating phenomenon on this planet. Biggest among them is the formation of symmetrical hexagon clouds and the rings with width around 10 feet. How can such symmetry and compression be achieved? These questions require immediate re-exploration of the planet with a new spacecraft with much better equipment but hold on!! other observations from Cassini might well force us to go back again.

Fuelled by the unexpected observations on the moons of Saturn the Cassini has filled our bucket of reasons for a future sequel mission. One of the primary objectives of the mission was to drop Huygens probe on Titan to study its atmosphere. All the instruments of Huygens probe were working and communicating with Cassini as it was falling toward the surface of the Titan. The presence of methane in its three forms like water is on earth came as a surprise to scientists. Under the thick fog on the planet lied a landscape of mountains with methane forming huge lakes which was simply stunning.

Water, ice, silica and organic compounds were detected by CASSINI when it passed
through plumes ejected from the surface of Enceladus. (Image:NASA/APOD)

Next began the exploration of second moon, Enceladus. There came the biggest surprise. Huge cracks were observed at the south pole of the moon. Cryo-volcanoes spew ice and water in the form of geysers at the speed of 12200 km/hr into the space and amazingly, some of water vapours were seen leaving the moon reaching far enough to form  E-ring around the Saturn.

To study the content of the geysers in greater detail, the trajectory of the spacecraft was shifted so that it flew right through the ejected plumes. As it passed through, its probes detected salty water ( with sodium chloride), pH similar to that of earth along-with silica sand and ammonia. Most of the spewed content was seen snowing back on the moon but some left its gravitational pull forming a ring around Saturn. One of the most breath-taking observation was the detection of organic molecules like methane, propane, acetaldehyde and propane. The origin of methane on our planet is predominantly of biological origin and its detection in Enceladus opens up the world of extra-terrestrial possibilities. 

In spite of all the discoveries, why are humans killing Cassini?

It is because as the space probe gets old the probability of anything getting awry increases substantially. As the instruments get old they might become unresponsive and loose the proper control of the spacecraft and its trajectory. When the spacecrafts are built, all the possible protocols are followed to prevent any contamination with earth borne microbes but some might slip inadvertently. On our planet we have specialised microbes which are termed extremophiles and those can survive extreme salt, pressure, temperature, heat and space. They are extremely adapted organisms and their independent evolution on these alien moons cannot be denied. One of the reason then to terminate this spacecraft becomes to prevent the moons of Saturn from getting contaminated with the extremophiles stuck on the Cassini. It doesn't matter if the probability of the collision is too low, but its death becomes a blessing in disguise as it opened a possibility of  a gutsier mission.

Bizarre Hexagon clouds, larger than Earth, are a permanent feature
at the north pole of the Saturn. (Image:NASA)

Earth as viewed by CASSINI from Saturn.
(Image:NASA

Indeed, Cassini's inevitable death brings an opportunity for riskier and courageous flyby close to the planet and its rings. Some tricky moves using Titan's gravity has altered the trajectory of Cassini which has resulted in GRAND FINALE.

It fills my heart with joy that right now a human build spacecraft is piercing through Saturn but at the same time little melancholic because the spacecraft will die this year. But the bright side is that as the participation of wider public increases, future science mission to these worlds might become reality.

By learning more about other planets and moons, our understanding of earth gets better. The appreciation of our world gets deeper. Humans are meant to explore and these mission feeds our constant need to know more about the universe. The famous quote of T.S Eliot can aptly summarise the entire space related quests. 

"We shall not cease from exploration. And the end of all our exploring will be to arrive where we started and know the place for the first time.."

Ten years later, the chromatin ice-breaker arrives..

I can still remember the days during my B.Sc. when I was preparing a poster on RNA interference (RNAi), that I struck something remarkable. Actually, there was a DBT sponsored event at our college and I was very excited to participate in a poster competition at my first ever scientific workshop. During that time, a lot of focus was on therapeutic aspects of RNAi and award of Nobel prize had already resurfaced the public interest. Apart from all the buzz around novel therapeutics, I was highly fascinated by the evolutionary implications of RNAi and its role in different organisms. As I read deeper and deeper I discovered that RNA interference not only acts as a defence mechanism or an immune system to ward off viral infection but it can also be used to regulate gene expression. It fine tunes the production of intermediate mRNA and regulates the final protein product inside the cell. 

Dr. Grewal feeling relaxed
after an intense
Q/A session !

Not only this, there were a shocker of findings which could easily flabbergast first-time readers. This observation was of a relation between RNAi and heterochromatin formation. Heterochromatin regions are condensed regions of DNA which are normally not accessible for mRNA formation. The opposite of that is euchromatin, which is a DNA region which can actively produce mRNA and later active protein. It was perplexing to put my head around the fact that small RNA fragments generated using the RNAi machinery could help maintain large scale heterochromatin across the genome. The very fact that the transcriptional machinery can access heterochromatin region, which was earlier thought to solely assemble at euchromatin was itself defying textbooks. 

The same RNA fragments which regulates gene expression was also observed to change the fundamental architecture of DNA domains and this was remarkably fascinating for me at that time. As I sought through the literature, one name which made attempts to address many fundamental questions on this theme was of Dr. Shiv Grewal. By then he was already making a buzz in this counter-intuitive field by observing phenomena reminiscent of billion years of shared history with the humble yeast. His path-breaking work that small RNA are required for heterochromatin formation in yeast had already made it to the prestigious breakthrough of the year (by Science magazine) . His dozens of articles across a decade or so in Nature, Science, PNAS and Molecular Cell forms a story which flows like a gentle stream. 

Every breakthrough over the years looks to fit like a square peg in a giant jigsaw puzzle presented by the nature. One thing which filled my heart with great joy back then was that he had his pre-doctorate education in Punjab district of India where I myself belong. Little did I knew back then that by chance alone, 10 years later I would be listening to his talk. The day came when he visited our university for a guest lecture. His beautifully crafted talk on his latest discovery regarding uniparental disomy greatly enhanced our understanding of genetic defects and cancer. It left the audience wanting more. His excitement, energy and eloquence was worth learning and I am sure he has inspired many more of my colleagues. 

When I requested him for a little conversation, he immediately agreed. It was very humbling to see such a kind gesture from a scientist who is carving the new frontiers in biological sciences. I am delighted to have a conversation with him and for the record, his previous conversation was published in PNAS when he was inducted in prestigious National Academy of Science last year. 

Below is the full unabridged conversation with Dr. Shiv Grewal. He is a distinguished investigator and Chief, at National Cancer Institute, National Institute of Health, U.S.A.

CuriousGuts: When I was reading your profile I found out that you have been working from 90’s and are coming with breakthroughs every one or two years. In fact every alternate year with an unconventional observation. When did it all start? When did your interest started in science?

Dr.Grewal: My personal interest in science started probably very long time ago. My father was an entomologist and he would often show me things, like insects which can exploit their plant host, I don’t know if you have seen that on the leaf surface the insect would lay the eggs and then the whole leaf would curl up. They produce certain enzymes that force the plant cells to follow their cues. So, my father would show me all those sorts of thing which made me very curious. But, off-course that is just a curiosity, that does not translate into you doing breakthrough research or even triggering you to be a scientist. But, that was the first time I got curious about how things work? How does nature really work? I sort of continued on with that and during my graduate school days.

But I think the question you touched in the first part about how would you go around addressing some key questions in the field that could potentially lead to breakthrough stories, that I think is something I learnt from my post-doctorate mentor Dr. Klar. He was off-corse of Indian origin and he passed away unfortunately too soon few weeks ago. He often would tell us that if you are going to be spending time doing research, you might well address a question, an important question in the field. Off-course, important question are often the difficult questions. I learnt that from him that don’t shy away, make an attempt and follow your own instincts and see if you could address those.

CuriousGuts: Like they say in war, you have to go in the direction where all the guns are blowing but in academia, if you go away from them you are bound to touch something important, as written by Edward O Wilson. All of your career seems to be shaped by this phrase. This phrase can aptly describe your work.

Dr.Grewal: One of the things which I do in lab, we often start with a small, simple observation. I could give you many examples of that. The most recent example, the UPD story, that I described to you in my talk. It was 1999 or 2000 that I was doing some genetic analysis of RNAi mutants, I noticed  that they do weird segregation and so for many years tried to convince my postdocs and nobody would go near that project because it was sort of not so easy to address that. So, I would try to do little bit of work here and there myself but the key point is that it started with a simple observation I made. We pursued that simple observation and it turned out to be an important observation, which led to a nice important story. that’s the way it has always been. we don’t go telling ourselves that I need to work on a project that would be a major story but we pursue observations which are from our own lab and we try to develop them, follow them and see where they take us. In my career I have been fortunate that they have often led to something important.

CuriousGuts: How do you deal with the avalanche of ideas. There are so many question. How do you prioritise which idea should be explored first? which hypothesis should be tested first before others? Doesn’t it keep you awake all the night?

Dr.Grewal: (Chuckles) There are many other things which keep me awake off-course, this is one of them. But prioritising science and your ideas is a very important thing. You really should be able to separate out in your mind what are the key fundamental observations that you would like to pursue or the questions you would like to pursue and I often do that in my quiet spare time at home. I like to work late at night and sometimes, it's a good time to go back, look at everything and then see where the key questions are. So, I don’t go around that I should do this project first or that project. I just go back and look at all the observations we have made in the lab and things which people have shared with me and look back at the key question which we should focus. Then, I would write that down, think about it and then arrange a meeting with my fellows and say, this is what I came across in my mind. I think we should be focusing on this. I ask “what do you think? Off-course, they are the one who will spend time working on them, they are important partners. and once we discuss that we come up with a plan. We would come up with a two or three set of questions and then pursue those and if we get encouraging results off-course then that defines the entire project.

CuriousGuts: How did the seed of heterochromatin got planted in your head? As you mentioned in one of your articles that it is an oxymoron, you specifically mentioned about the transcription happening inside heterochromatin. We rarely get an example of oxymoron in strict biological sense but I think this makes through it. How were able to think something this unconventional?

Dr.Grewal: This goes back to my graduate school days at Cambridge. I would often hear people talk gene expression where transcription factor comes to gene and turns the gene on or off. I would often also hear, Jean Thomas taught chromatin biology at Cambridge and she would often talk about large domains of gene silencing. Although, in those days most of these things were defined genetically. The genes are off but nobody really knew the structures and modifications. So, I developed this idea that I am going to work on a domain level control of gene expression. Then I looked around and I came across some articles where my post doc mentor Dr.Klar’s lab had published that there is a domain in Schizosaccharomyces pombe genome which is fairly large in yeast cells 20-30 kb large and you never see any recombination happening in those domains. So, it is recombinationally cold.

You never see meiotic recombination happening. So, I wrote to him, Do you know what exactly happens? that why is that large domain not doing any recombination? In yeast 3 kb is one centimorgan.  Every 3 kb should give you a certain level of recombination events. He replied me back that you know “Do you want to work on that?” So, I went naively thinking that he has a region cloned and I am going to find out exactly what is happening there. He told me that No, they actually do not have that region cloned. In fact the genome project working with pombe genome doesn't’ work with strain those have that region, cenH repeats. So, I cloned the whole thing by hand and I sequenced it by hand. All the 30 kb. I found a repeat element. Other postdocs made fun of that there is not even a gene to work on. So, I pursued that repeat element, I deleted it and it affected silencing in that entire domain. Later on, the same repeats turned out to be target of RNAi and many things pursued from there. Once I knew that the large domain is controlled by repeats, So it led to the mapping of histone modifications, that pattern of modification later on turned out to be conserved in mammals.

But just to give you a taste of what I mentioned in my talk also, I got ridiculed many times by other members of my lab who would often tell me that there is nothing really there for me to work on and I am wasting my time. I stuck to my belief and pursued to that and it became my career.

CuriousGuts: Yes, a lot of times young researchers, many friends of mine feel let down. How did you keep it up?

Dr.Grewal: If you think you are upto something. Your own thinking and your own belief is more important. Rather than other people define questions for you, you have to define them for yourself. By that I mean, you have to believe in yourself.

CuriousGuts: and the repeat story which you were narrating was also discussed in Proceedings of National Academy Q/A section also.

Dr.Grewal: Yes, yes.

CuriousGuts: Has it ever occurred to you that hypothesis which you are building for yourself and find online that there has been work which has already been done, Has it ever happened with you?

Dr.Grewal: Science is a collaborative endeavour. No one person is going to figure out every thing, We all feed of other people, things we do other people build on them. Other people do certain things which i learn from. So, at the end of the day I look at science more like this. There are important questions in biology. Epigenetics is hot field now. We need the answers to those questions, So that we could make progress. Now, one brain only can do so much. All the brain powers put together, we could accomplish more. So, I am happy if other people are making progress particularly at this point of my scientific career. I am happy that other people are picking up on things we work on and other they work on. It is important from the young scientist point of view that their ideas are unique in the sense that they can pursue their scientific careers but science again is a very very collaborative endeavour. We shouldn’t be afraid of other people making progress. We should look at it in fact, we have a common goal. How can we help each other get there.

CuriousGuts: One of the first breakthrough which you achieved was that if we silence RNAi machinery in fission yeast we see that heterochromatin regions do not form. Second, there is absence of small interfering RNA. So how did you connect these dots?

Dr.Grewal: We do everything in lab which starts with some genetics. We knocked out RNAi factors and we noticed heterochromatin defects. In fact, I noticed the first observation that the segregation 0 to 4, 4 to 0 segregation. In previous times people have argued that defects in heterochromatin assembly could give you segregation defects. Although those segregation defects are different. So it was sort of one of those things, lets see what happens. It had heterochromatin defects, and we had just found the pathway where  we had shown methylation of Lysine 9 , HP-1 recruitment, so, we studied all that. We had already seen artefacts in all that.  But we had not picked any small RNA at that time. In parallel, their was work published from Criag Mello lab who did his screen in Ceanorhabditis elegans and he identified C.elegans argonoute in his screens  for RNA- defective mutants. So, when his paper came out we realised that we are working with argonoute which is required for small RNA, RNAi and all other stuffs. So, we learned from their work. (that is in 2002) Yes, this is related to your earlier question. Two labs pursuing something totally different directions help each other. He wasn't studying heterochromatin, he was studying RNAi. We were studying heterochromatin. His identification of argonoute as RNAi factor helped us realise that we are working with RNAi factor. So we linked RNAi to heterochromatin. And in all that your observations are key to all this.

CuriousGuts: But after some time in one of your research publication you showed that RNAi-independent heterochromatin formation also takes place at low efficiency. So, were you able to detect basal level transcripts when you earlier published in 2002?

Dr.Grewal: When you delete RNAi  machinery or you delete the element on which RNAi acts, predominantly at MAT Locus. You still have stochastic low level formation of heterochromatin. which once assembled can stay there for very long time. So we knew there got to be another pathway bringing heterochromatin in that region.

CuriousGuts: So you knew at that time that parallel mechanism exists?

Dr.Grewal: The genetics told us there got to be one because in absence of RNAi cells could form heterochromatin but at a very low level and in a stochastic manner we realised that there got to be another pathway. So the question was what that is and one of my post doctoral fellow was able to figure out those transcription factors. I realised that these Transcription Factors have become a very hot topic now, In flies they find that those factors are required for reprogramming gene expression and many other labs pursuing these factors.

CuriousGuts: One of your observation was that transcription factors were binding but not extending. The localization TF III without polymerase RNA pol III binding. why didn’t RNA pol III got extended?

Dr.Grewal: That is totally different to forming heterochromatin. that is more to do with how do you restrict heterochromatin in a given domain. So, a different postdoc Noma identified these boundary elements when he mapped the whole modification map and he found these abrupt ends. One side is heterochromatin and other side is euchromatin. So, he found these boundaries and he went after trying to find whats really forming those boundaries and he identified that there is a binding site for TF IIIC and for some strange reasons he found that TF III C alone. I think simple answer to that is in addition to TF IIIC  there are additional things which are required to recruit RNA Pol III. So, TF III alone is not sufficient to bring pol III.

CuriousGuts: One of your another observation in which HDAC’s (Histone Deacetylase). clr6, were identified as of two types one binds on the promotor of the genes and other on the centromeres. How were you able to detect those two different types of clr because they might have looked the same?

Dr.Grewal: So the way you do it is, we start out with genetics. I did a screen many years ago and identified these mutations. To find exactly about what they do we go through a systematic analysis scheme. we purified them and found out that they were in separate complexes.  we then tried to find out where those complexes were localised and we found by ChIP-chip analysis that they were localised to different places in the genome. That’s the sort of scheme we followed. As their subunits were different we have used them to target  their complex.

CuriousGuts: One of the predominant theories of the 80’s  was selfish gene in which gene is a selfish unit and it wants to survive even at the cost of host. One of your paper focused on centromeric protein B. One of the most beautiful observation regarding its activity to stop the extinct transposon from entering the genome. when did you know about this? It perplexed me completely.

Dr.Grewal: The fact that it was so perplexing, thats why the paper is published as an article in Nature. That is called host genome defence by transposon derived proteins. So, what the transposon which are being recognised by CENP-Bs transposases are slightly different, these are transposes derived CENP-Bs proteins which are targeting another class of transposons. So, I  first though that this is something which is special happening in evolution but I have been told that by evolutionary biologists that this has happened more than once in evolution where the transposon derived protein is used by host are being given a function where they are doing something really interesting. So, we found in that paper this is work of H Cam, who used to be in my lab. He found when he mapped them, unlike their names centromere binding proteins B they were actually binding to retro-elements and they recruited HDAC’s. to silence retrotransposons.

CuriousGuts: How many more of these unknown elements are waiting for their discoveries in our genome!

Dr.Grewal: As I told you in my lab things start with simple observations. Now, how many of those are important observations that would lead to some of the important discoveries. I could not really comment. It will all come out as the time progresses.

CuriousGuts: Another beautiful observation about the timing of phospho- methy- switch. There is very brief timing in which all of that happens. How does that become accessible for brief period of time?

Dr.Grewal: The original observation that the phospho- mark next to methyl- mark on serine 10 lysine 9 respectively, was work from other group. They found that the phosphorylation mark on the serine next to lysine 9 could neutralise the silencing effect and chromodomain proteins cannot bind  methyl- mark and there is no assembly of heterochromatin, that disrupts heterochromatin formation. It turns out that phosphorylation happens by aurora kinases during mitosis. So, that disrupts heterochromatin, so that other factors could come by and bind to that. But we build that case on other group and that wasn't really a straight out work from us. We just used that in context of cell cycle control of heterochromatin.

Dr. Shiv Grewal giving a talk at our university.

CuriousGuts: You showed that if there is premature termination, those transcripts could be used for heterochromatin silencing?

Dr.Grewal: That is a very important question. One of the major conundrum in the field that if a transcription is required for forming heterochromatin then why aren’t we building heterochromatin on any genes because those are transcribed too? what defines a transcription which is feeding into heterochromatin versus transcription which is producing a novel functional transcript? So, V R Chalamcharla in my lab did some work to figure exactly that. He found that the transcription which is giving  a heterochromatin, there is a one big difference. In normal transcription of any gene you have a transcription initiating from a  promoter and Pol II travels all the way to the end of the gene, to a termination site. Termination factors are assembled, they release the pol II and transcript is released as functional mRNA. He found that one which were building heterochromatin were different were not terminated by same termination factors. They were terminated by MTRAK RNAi. RNAi and MTRAK somehow, as I mentioned cryptic introns and DSR motifs binding site for some of these factors. When a transcript is being made, if cell sees a motif they bind there. RNA binding proteins bind their and recruit bunch of these factors. They do two things :- they terminate pol II which is not at a normal termination sequence, they assemble another specialised complex and at the same time they degrade the RNA. So, the RNA degradation and non-canonical termination, which is done by different set of factors is a way by which cells can differentiate functional transcript from transcript for heterochromatin formation.

CuriousGuts: So RNA dependent RNA polymerases forms a double stranded which is substrate for this type of mechanism. but this enzyme is not present in us. Is there any homologue in human?

Dr.Grewal: Thats very important enzyme. Even though they are not present in us the PIWI pathways and these small RNA’s based pathways are still present.  You probably had heard about the ping-pong model of argonoute.  Those sorts of mechanisms do exists which can bypass the requirement of RNA dependent RNA polymerases. So small RNAs get amplified through different mechanisms. Plants, C.elegans, Schizosacchromyces Pombe these all have RNA dependent RNA polymerases but other systems have different ways of doing this.

CuriousGuts: Thank you so much for your time.

Dr.Grewal: Thank you.

Origin of life after mere 400 million years of earth's formation!

Origin of life is one of the biggest mystery of our times. Various hypothesis have been proposed from time to time but origin of life near hydrothermal vents has emerged as one of the most plausible one. There are swathes of ecological systems discovered at the sea bed which are completely cut-off from the photosynthesis based life which we have extensive knowledge. Many elements and organic compounds have been detected in the plumes emanating from the hot core of the earth. The presence of oceans soon after the origin of earth have strengthened the idea that our early ancestors could have emerged here. 

Now a study done by Dodd et al. have discovered fossilized micro-organisms nearly 4.2 billion years old in sedimentary rocks in Quebec Canada. Before this discovery previous record for oldest confirmed fossils are not older than 3.5 billion years. This is a giant leap in terms of hardcore evidence which places us now back by nearly 700 million years. 

The key analogous structure which this study found share a similar morphology and mineral composition with existing hydrothermal vents organisms.Basically, Iron metabolizing ancient microbes left the traces e.g. formation of multiple tubes from a single hematite source at varying angles which would not have formed naturally without any biological input. Similarly, coiled, branched and twisted filament structures cannot be explained by any abiogenic pathway. Interestingly again, extant microbes still produce hematite tubes and filaments around hydrothermal vents. These filaments gets coated by silica and later Iron oxyhydroxide in successive venting. Similar knobs are also created by chemolithotroph Leptothrix-type bacteria. Other than that twisted morphology is formed by a proteobacteria called Mariprofundus.

Conditions near hydrothermal vents could have supported
primitive life. These types of vents might be present on
Europa or Ganymede.

These fossilized remains of ancient micro-organism shares stark resemblance with the organisms still living on this planet. The discovery not only fuels debate regarding origin of life but also extraterrestrial life. The fact that these ecological communities with its entire food web can survive even in the absence of sun is simply fascinating. At the time when terrestrial and oceanic life would dwindle in the absence of sun, these communities will continue to thrive as if sun never existed. The range of organisms from chemolithothrophic microbes to crabs, eels and fishes form similar food chain of predator and prey as other oceanic and terrestial organisms form. We can use this knowledge to detect life not only on our planet but other unknown worlds too. The moons like Ganymede or Europa might have underwater hydrothermal vents and who knows what type of ecological communities are lurking beneath these frozen wonder.

Reference:

Dodd, M. S., Papineau, D., Grenne, T., Slack, J. F., Rittner, M., Pirajno, F., ... & Little, C. T. (2017). Evidence for early life in Earth’s oldest hydrothermal vent precipitates. Nature, 543(7643), 60-64.

Video of light at 100 billion frames per second!

Speed of light is  captured on camera for the first time with this 100 billion frames per second camera!

This compressed ultrafast photography  can capture 1011  frames per second. 

Refer:

Gao, Liang, et al. "Single-shot compressed ultrafast photography at one hundred billion frames per second." Nature 516.7529 (2014): 74-77.

Awe-inspiring experiences at GIAN

I had a great opportunity last week to attend a GIAN (Global Initiative of Academic Networks) workshop on 'Post-transcriptional Control of Gene Expression in Eukaryotes' coordinated by Prof. Arthur Garfield Hunt from University of Kentucky, USA. He can be appropriately called 'RNA guy' in Plant biology as his work on RNA, poly-A tailing of mRNA alongwith RNA viruses has led to increased understanding of the natural world. He presented a series of talks for 6 days at our university. His topics ranged from kinetics of mRNA turnover to gene sequencing. Upon my request he generously devoted time for a quick interview. Below is the unabridged text of the conversation.

CuriousGuts: First of all Dr. Hunt, your talks were beautifully presented. I was just wondering if we could just learn to keep our slide minimalistic, without any clutter yet so rich in substance, that would be wonderful. I would like to go back, I was just curious to know when were your first exposed to science? How your interest developed in science?

Dr Hunt: I would say in probably first grade or second grade and it just developed spontaneously. My parents kept a lot of books around and the science books interested me. My teachers in early education kind of encouraged me and it seemed like a good fit. 

Prof. Hunt still smiling with
the culprit who reduced
the entropy of his tea!

CuriousGuts: What are your favourite books? I have read books by Carl Sagan and his documentary inspired me to jump into science. Along with, Earnst Mayr, Richard Dawkins, Stephen jay Gould , Neil Degrasse Tyson. I myself derive lot of inspiration from the books. I would like to know about your favourite books?

Dr. Hunt: My favourite books are history books. My hobby is I think curiously enough to read about world war 2. I try to expand my knowledge from what I learnt in school. Americans don't learn about Russia, I think it is important to understand Russia and other places that Americans might see adversarial. 

CuriousGuts: I myself got interested in world war 2 and sometimes it comes inspirational to me when I struggle with an experiment then I imagine as if what was it like sitting on that boat during Normandy landing and then I de-stress by putting my experimental problems in perspective. Does that happen to you?

Dr. Hunt: My interest in history is to try and keep a bigger perspective. So, science is international. To try to limit unconscious biases that one might have for other scientists or people from other countries or so. I find my interest in history and things I learn help me along those lines.

CuriousGuts: How does it feel to you, as you have come from an era when these space exploration began, the time when genetic code was decoded, now we have a plethora of information like genetic sequencing. How does it feel to be a part of three scientific generations . now so much is there. how does it feel to you? 

Dr. Hunt: When I started in science it was a Ph.D thesis to sequence maybe 300 base pair very small gene and now I can have an undergraduate student sequence an entire genome in a week. so when I think about this is mind boggling . It is very humbling and when I think about it little bit more I get very optimistic about the future. So, i look at where we were in 1976 when I started graduate school and where we are now I imagine by the next forty years the progress and whats awaiting us, i mean i can’t imagine where we would be. 

CuriousGuts: Was that in your thoughts that we would jump so much like moore’s law what they call? 

Dr. Hunt: Not at all. I have been swept along by advances in technology. I have to admit that probably I was skeptical about the intentions of human genome project , plant genome projects in 1990’s . I was skeptical that it was worth the effort because in 1999 the effort was tremendous and expense was tremendous. 

CuriousGuts: As we go along we see plethora of information in our databases but crisis emerging among them is of reproducibility. we see retractions, we see that biological data which one lab generates sometimes looses significance in other labs . As we are delving into big data sciences and mega scientific projects reproducibility continues to be a major challenge. and as more complex and advanced things get incorporated the threat magnifies. what do you make of this scenario? 

Dr. Hunt: My basic attitude toward scientific literature is absent - like clear or out right fraud or something. second, there is a hint of truth and accuracy in every experiment. sometimes you have to take the time to find what is consistent but everyone who sets up an experiment reports the result accurately. if there is irreproducibility it reflects factors, variables beyond one’s anticipation.

CuriousGuts: The experimenter might be homes enough but multifaceted nature of variables. but a study done by a private company found out that major scientific claims made by several paper on cancer were found to be untrue. the key experimental results could not be repeated. what do you make of this? 

Dr. Hunt: I am aware of that story. honestly, I would like to see all the results that the company generated to be sure that their claims were accurate. Again, my attitude is that there is grain of truth in every honestly performed study and you just have to be willing to accept that something maybe different in different groups but done properly there is truth in an experiment.

 CuriousGuts: There are some challenges which I want to be solved during my life time like dark matter, stem cell use in wider therapies, vaccine against tuberculosis, better batteries so that we don’t have to charge phone enough. I want to see these and many others to be resolved during my lifetime. when it comes to plant biology, what would you like plant biology to achieve immediate future and distant future? 

Dr. Hunt: I have to think about that a little bit. So, I guess from a practical perspective I guess just a better understanding and ways to better respond to crisis that might arise due to global warming. because this will affect crop production in the world perhaps moving along and better tailoring crops for nutritional purposes. Enhancing the utility and yields of crops in a changing world. 

CuriousGuts: At an academic note I want to know about your coping strategy for the phrase ‘the more we know, more we realise how less we know’

Dr. Hunt: Certainly I am aware that the more I know the less I know. So my attitude to this is that iI view myself as a kid in candy store so I got a gum ball out of one machine and now I have big rack of candy back there and once thats gone I have to move to other.

 CuriousGuts: You have had a beautiful journey in science. If you had to sit in a time machine and go back, what suggestion would you like to give to your younger self? 

Dr. Hunt: This is a difficult question because to be perfectly honest I am very happy with the trace of my life from becoming interested in science to what i did. i knew i was going to be biochemist when i was 16 years old. I am very happy the way things have turned out. I cant think of much advice for choosing a different path or trying to do things differently. I was very fortunate to have excellent mentors. My advice would be that if you feel that you are stuck and you are not going to reach a conclusion in the day to day or in 10 to 20 years just keep persisting because if you got a plan and it makes sense, talk it over to your mentor and keep to it. There would always be roadblocks but you have to keep faith. 

CuriousGuts: There is a trend now-a-days in which applied project are given disproportionate more priority over basic projects. when the pressure of final molecule or vaccine or resistant crop is higher than understanding the basic science how do you assess this situation? 

Dr. Hunt: I agree that basic science is under-appreciated and under-funded. The point I usually make is that any applied project or application or translationary research is grounded in thousands upon thousands of studies performed in basic research laboratory. It can be viewed like a plant system, there are fungi which exists underground like a huge network of rhizomes or fungal mass and up through this comes a vegetative shoot or mushroom. So, the vegetation shoot, translational research, application doesn't exist without the huge mass underground. So, I don't know how to convey this message but I think it is an accurate depiction of the relationship between basic and applied research. 

CuriousGuts: How do you keep yourself so up-to-date? I mean I hear all the cries from my graduate mates that its tough to keep up with literature. what is your routine with regard to this because you seem to be very updated in your field? 

Dr. Hunt: It’s a good question. there is way too much to keep up with. So, I get couple of journals in my lab, in my office I have newsreader or feed which rolls the titles and abstracts from probably 20 journals, which I keep up with from time to time. every one and then if I encounter a subject which I feel I need to know more about i simply turn to Mr.Google. So, between google and pubmed you can catch up pretty much everything. The google is good because you get leads to more popular or lay press which leads you to perspective which you don't get just if you are buried in a journal. 

CuriousGuts: If we see at popularisation of science, there are very few documentaries and books on plants. We can find a lot of documentaries on the universe or wild animals but we have only handful on plants. Private life of plants narrated by David Attenborough was made long ago and has not been continued till then. popularisation of plant sciences seems to be on nobody’s agenda. why don't you write a book on these lines? 

Dr. Hunt: This is discussion that American Society of Plant Biologists have regularly. the society does not ask its member to write a book but they want to engage in social media, and have much more involved in outreach and education at primary or kindergarten level.

 CuriousGuts: Thank You Sir for your time.

Tasty yet deadly litchi, the update.

 http://www.thelancet.com/pdfs/journals/langlo/PIIS2214-109X(17)30035-9.pdf

Litchi is one of the tastiest seasonal fruit which is quite popular in India. It has notoriously poor shelf life, which makes it costly at times. I have enjoyed this fruit from my childhood but its evil side was revealed in the year 2014. I still vividly remember that more than 100 children, aged 15 years or below suddenly died of idiopathic neurological disorder. Many hypothesis flew around, from the widespread usage of pesticide to infectious disease but nothing was established. Now, a case control study published in journal LANCET clears the air further although molecular reasons behind this mystery began to emerge much earlier. We must not forget that similar findings were earlier reported in the journal CURRENT SCIENCE by Dr. Mukul Das in 2014, followed by later correspondence in 2015. Keeping the controversy aside the underlying mechanism is really interesting.

Mortality was observed to be significantly high in malnourished children who skipped their evening meals. The normal stores of glycogen in liver is sufficient for short term energy needs in normal healthy children, which is followed by oxidation of fatty acids in an event when glycogen stores are depleted.  Now, in malnourished children this step is short-circuited with direct activation of fatty acid oxidation, in the absence of glycogen. Two naturally occurring molecules in litchi, hypoglycin A and methylenecyclopropylglycine (MPCG) , are known to disrupt fatty acid metabolism, which in turn greatly reduce the glucose levels in the bloodstream. The poor supply of glucose further caused irreversible damage to brain, followed by seizures and unconsciousness.  

http://www.currentscience.ac.in/Volumes/109/12/2195.pdf

Hypoglycin A has been earlier linked to hypoglycaemic  encephalopathy in Jamaica. It is abundantly present in ackee fruit, which is from the same soapberry family as litchi. Both these molecules have been known to induce similar symptoms in animal studies.

Most of the deaths in India were reported in families of litchi harvesting labourers. As the Current science correspondence revealed, the singular fruits dropping on the ground were left for consumption by children as litchi is mostly sold in bunches. The heavy intake of fruit along with skipping of evening meal worsened the situation. Public education and simple intervention steps as healthy cooked evening meal and infusion of dextrose in case children are rushed to the hospital is already saving many lives.