Dr. Saikrishnan Kayarat’s team @ IISER Pune Published in Nature Chemical Biology.


       Like many other life forms, bacteria too are prone to viral infections. Many bacteria harbor restriction endonuclease enzymes, which help check the infection by selectively cutting and destroying the viral genomic DNA. The perpetual tussle between bacteria and viruses to gain an upper hand has resulted in a battery of restriction enzymes of different complexities. There are the simple nucleases that cut DNA at target sites – two copies of the nuclease come together, each cutting a strand to slice the double-stranded DNA. And there are motor-driven nucleases that are massive in size and use chemical energy to cut DNA only upon collision with another such nuclease and away from the target sites. A collaborative study between a team of scientists at IISER Pune and the University of Bristol, UK, of these energy-driven nucleases, published this week in Nature Chemical Biology, reveals a new mechanism of DNA break formation involving a compound damage caused by DNA shredding rather than slicing.

Dr. Saikrishnan Kayarat’s team at IISER Pune has solved the first atomic resolution x-ray crystal structure of a motor-driven restriction endonuclease bound to DNA. They found that contrary to the prevalently understood mode of action, the nuclease domain of this class of enzyme is positioned such that when two enzymes collide on a DNA, the nuclease domains are distant from each other. This structure also happens to be of one of the largest single-polypeptide chain bound to nucleic acid determined to date.        

             Guided by the structure, Prof. Mark Szczelkun and colleagues at the University of Bristol used single-molecule biophysical approaches, to find that the nucleases use the energy derived from the cellular fuel, ATP, to run along the DNA. Using biochemical approaches they found that upon collision, the distantly spaced nucleases make multiple nicks on the individual strands, thus shredding the double stranded DNA. This is in contrast to a clean-cut slicing brought about by the action of an enzyme with an apposed pair of nuclease domains. Unlike a sliced-DNA, a shredded DNA cannot be easily repaired.

The paper titled “Translocation-coupled DNA cleavage by the Type ISP restriction-modification enzymesand authored by Mahesh K. Chand, Neha Nirwan, Fiona M Diffin, Kara van Aelst, Manasi Kulkarni, Christian Pernstich, Mark D. Szczelkun and Kayarat Saikrishnan has appeared as an advance online publication of Nature Chemical Biology.

This work received funding from Wellcome Trust-DBT India Alliance; Wellcome Trust, UK; DBT India; and CSIR India.

Original News : IISER Pune.


Double Treat for Bird Song lover & Music Lover : Beatboxing

Image : NCBS

By Anusha Krishnan

Beatboxing is the art of vocal percussion, and one could say that birds are the masters of beatboxing.  In a contemporary approach to music and social awareness, a bird ecologist, a photographer and a musician have collaborated to create the unique #SkyislandBeatbox project. The trio – V. V. Robin (the ecologist), Prasenjeet Yadav (the photographer) and Ben Mirin (the musician) – enthralled their audience at the National Centre for Biological Sciences (NCBS) with their Birdsong Beatbox performance.
“The overwhelming response was unexpected and I was not sure what to make of it. It wasn’t just in NCBS – our shows in Cochin, Kodi, Trivandrum and Ooty rocked!” says V. V. Robin.

“The experience was all about portraying the birds as the heroes. We wanted to draw attention to the music, not the musician; the science, not the scientist and the photos, not the photographer”, says Aparna Banerjee, one of the curators of the #SkyislandBeatbox initiative from NCBS.

Ben’s music on a beatbox with bird calls from the Western Ghats coupled with Prasenjeet’s footage of these birds created a smorgasbord of audio-visual excitement. “The NCBS show was a really strong capstone to our team’s tour through the Western Ghats. We ended up modifying our structure to make the pieces more integrated and I think it really paid off. It was obvious that everyone in the room really enjoyed the music but also had a deep interest in our process and the science behind it. I’m really excited to see where this model can go, it’s as much about the team as it is about the message,” says Ben Mirin.

Current research by V.V. Robin in collaboration with Uma Ramakrishnan of NCBS shows that some of the birds featured in the program are very special – they are endemic to (which means they live only on) areas called sky-islands. Sky-islands are essentially the tops of mountains that are separated from each other by a “sea” of valleys. They are unique habitats that are in danger of disappearing due to deforestation and climate change. The presentation takes an innovative approach to spreading awareness about the very real dangers of extinction that loom over the wondrous bird life in the Western Ghats.

The effort has been funded by National Geographic, the Indian Bird Conservation Network (IBCN) and the Shola Trust.

For an example of Ben Mirin’s musical work, please click here.

A Must watch Video : Music Made from Real Bird Songs By Ben.

Original News : NCBS News



Cori Bargmann Puts Her Mind to How the Brain Works

Image : nytimes.com


– In conversation with Claudia Dreifus, NYTimes

Cornelia Bargmann, a neurobiologist at Rockefeller University in New York, studies how genes interact with neurons to create behavior. Two years ago, President Obama named Dr. Bargmann, who is known as Cori, a co-chairwoman of the advisory commission for the Brain Initiative, which he has described as “giving scientists the tools they need to get a dynamic picture of the brain in action.”

I spoke with Dr. Bargmann, 53, for two hours at the Manhattan apartment she shares with her husband, Dr. Richard Axel, a neuroscientist at Columbia University. Our interview has been edited and condensed.

Q. As an M.I.T. graduate student, you made a discovery that ultimately led to the breast cancer drug Herceptin. How did it happen?

A. What I did was discover a mutated gene that triggered an obscure cancer in rats. Afterwards, it was discovered — by others — that this same gene is also altered in human breast cancers.

Since our work in the rat cancer showed that the immune system could attack the product of this gene, Genentech developed a way to deploy the immune system. That’s Herceptin. It is an antibody against the gene that sits on the surface of a cancer cell. It can attack the cancer cell growing because of that gene.

Q. Currently, you spend your time trying to understand the nervous system of a tiny worm, C. elegans. Why do you study this worm?

A . Well, the reason is this: Understanding the human brain is a great and complex problem. To solve the brain’s mysteries, you often have to break a problem down to a simpler form.

Your brain has 86 billion nerve cells, and in any mental process, millions of them are engaged. Information is sweeping across these millions of neurons. With present technology, it’s impossible to study that process at the level of detail and speed you would want.

Now, about 25 years ago when I was transitioning from cancer biology to neuroscience, this little worm’s brain had just been mapped — every connection between every nerve cell and the brain. That’s roughly 7,000 connections and 300 neurons. You could look at a brain cell — which you could see because the creature is transparent — and say, “I know what that cell does. I know what it’s connected to. I know what genes it expresses.” For a researcher, that’s a lot.

Q. But is a simple worm really an appropriate model for studying the human brain?

A. Most of what we know about the human nervous system, we have learned from simpler animals. The most famous animal in neuroscience is the squid because it has these huge nerves that enabled people to understand the basis of the electrical transmission of information.

In fact, one of the biggest surprises in modern biology is that the genes are not that different between the different animals. Almost every gene we are interested in with humans is recognizable in a mouse. Most are recognizable in a worm or in a fly.

Q. So what have you learned from your worm?

A. In 1993, we did an experiment showing that worms could smell. This wasn’t known before. Our next experiment, I think the most important my lab did, is that we made a worm neuron smell an odor it had never smelled before, and we made the animal completely change its opinion of that odor by doing that.

We had an animal that loves an odor that smells like a certain food it likes. Usually, the worm runs right toward the odor. We took the gene that is a sensor for the food from where it was normally supposed to be. We put it into a different neuron that senses things the worm finds dangerous.

Then, we “asked” the worm what it thought of this smell it usually loves. It ran away from the smell, as if it were dangerous.

This said that the odor-sensing nerve cells form an innate map where each one knows whether something is good or bad about the environment. There’s a completely unlearned internal set of preferences, a set of instincts about what’s good and bad.

Q. For the past two years, you’ve headed the advisory committee to the Brain Initiative. On the phone, you told me that the experience made you into a better scientist.

A. In the lab, you have to make choices about what you think is important. On this commission, we had to do something similar.

Our problem was this: There was an appropriation of $100 million for the first year. That’s a limited amount of money. We didn’t want to be in a situation where you’re giving $14.99 to every neuroscientist and calling that a Brain Initiative.

So then, what to invest in that will move the science forward? What parts of the field are coming along? What is science fiction? Eventually, we came to an agreement on a basic outline: Use the money for mapping brain activity in circuits and networks.

The first step is to create new and improved technologies to study the brain. With better tools, all of neuroscience will move forward.

The second step is to apply those technologies to make discoveries about how the brain functions. The theme is understanding brain activity, the flow of information through millions of interconnected nerve cells. The long-term goal is to use that knowledge to help prevent and treat brain disorders. That may be decades or more away.

Q. Some of your critics have complained that you don’t have enough funds to tackle such a huge question.

A. I do not think that the goal of the initiative is to map every connection or detect every neuron firing anywhere in the brain. The goal is to develop and apply new ways of studying networks of neurons involved in thought, emotion, perception and action.

Q. In recent weeks, there’s been a lot of renewed discussion of the role of women in science. Have you encountered much gender bias?

A.  On the whole, no, though on my graduate school interviews, I do remember someone asking why I should take a slot in graduate school when I was probably going to get married and have children. I thought, “You dinosaur!”

I didn’t get that message every day. I actually got a lot of encouragement. At M.I.T., I had a wonderful Ph.D. adviser, Robert A. Weinberg. In his lab, there was a postdoc from Europe who used to call the women “the bossy ladies.” One day, Weinberg heard this, and he took the postdoc into his office.

When the postdoc came out, he was pale. We never heard anything about that again. Weinberg is really a mensch.

Q. What were you like growing up?

A. I read indiscriminately. I enjoyed mystery stories. When I read “Microbe Hunters,” it seemed scientists were like detectives following a set of clues. Some clues were red herrings. Discarding them was an important step to getting to the right idea.

Original Source : The New York Times.