02 Mar

Mechanism of Nuclear Pore as exploited by Influenza

Importin Alpha (in green)

An Influenza virus is typically about the size of 70 millimicrons or a thousandth the width of a single strand of spider-web. To reproduce, viruses should be able to pass on their genetic message and often an enzyme to translate that message, the viral polymerase. The polymerase enzyme is crucial in bringing single monomers or nucleotides of DNA together, catalysing the polymerisation of DNA when a gene is copied. The conformation of the enzyme, or it’s shape, is crucial to it’s function. The virus, needing the host cell’s metabolism to survive, targets the cell’s nucleus. Isolated from the rest of the cell by the nuclear membrane, the nucleus is an ideal site for the replication mechanism. The gatekeeper proteins such as “importin ∝ ” are selective about the molecules that make it within the nucleus. In the case of influenza h5n1 researchers at The Institut de Biologie Structurale have been able to show a previously unknown conformation to the viral polymerase. This alternate conformation allows the polymerase to reach within the nucleus, attaching itself to the importin ∝ . It then has to acquire the conformation to be functional as the polymerase, replicating the viral message. What is interesting is that the polymerase’s conformational change is that it is dependent on a change in the temperature of it’s medium. A change in temperature can now be linked with a change in the polymerase’s efficiency. This could be why there are different rates of mutations of Influenza H5N1 within it’s avian and mammalian hosts.

Diagram of a Nuclear pore with Importin marked as 5

Reference:
F. Tarendeau, J. Boudet, S. Cusack, D.J. Hart et al. Structure and nuclear import function of the C-terminal domain of influenza virus polymerase PB2 subunit, Nature Structural and Molecular Biology, 25 February 2007
09 Sep

We get hiccups because we lack gills

As featured on Brainwave|Amar Chitra Katha

Tanvi’s trying to stop a hiccup

Have you ever wondered why we get hiccups and why they’re so hard to get rid of? Is there a way out?

The part of our brain that is signalling us to hiccup is the brainstem. This is the same brain segment that directs swimming amphibians such as frogs to push water through their gills. In his book Your Inner Fish: A Journey into the 3.5-Billion-Year History of the Human Body, Neil Shubin, an anatomist at the University of Chicago, says that maybe this isn’t coincidence.

Source: Anatomography, maintained by Life Science Databases (LSDB) View License

As a foetus swimming in our mother’s womb, each of us had slits in our necks that were very similar to gills! We lost them by the time we were born, because we no longer needed them.

Shubin thinks that the brainstem’s habit of sending signals to gills got passed on from our amphibian-like ancestors. We may have lost gills along the way, but it seems that the gill signals stuck on. What happens when we have no gills to receive the signals? Hiccups!

A few years ago, in 2003, Christian Straus–a French scientist–showed that even though we humans don’t have gills anymore, the circuits in our brains that control them still exist. When there is a lack of oxygen or a rise in carbon dioxide around the throat (this often happens when we laugh a lot, or eat spicy food), these circuits get triggered. In creatures with gills, this would activate the gills, but with us it just causes a spasm, also known as a hiccup.

09 May

About the spirit of Exploration.

“The people who were putting up millions of dollars were asking my father, ‘So, Captain, what do you expect to find?’ and his answer to those people who were about to make major commitments was, ‘If I knew, I wouldn’t go.’”

Jean-Michel Cousteau, 2005

02 Oct

Science in Action

http://blogs.scientificamerican.com/at-scientific-american/2014/09/21/putting-science-in-action-in-swaziland/

 

The Swazi, Solar Cities Team.

The Swazi, Solar Cities Team.

 

When Google announced that there would be a science in action award for the Google Science Fair 2012, I wasn’t quite sure what it meant. Aug 2014, 3 days and 10,000 kilometers from Bangalore my brother Rohit Fenn and I, Amit, stepped out on our first visit to the African continent. It was T.H. Culhane‘s idea and his enthusiasm that brought us here with our tent and backpacks. Science seemed a far cry from my aseptic college lab. But if the google science fair taught us one thing it is that a dash of science and a whole lot of attitude can make a difference in the world we live in. In the 31 days we were in Africa we met with people from 20 nationalities heard 11 languages stayed in majestic homes and in the outdoors in our tent. All this for 7 days of a “Science in Action Camp: to explore technologies that have the potential to change the world. If anything, Science in Action is the Tower of Babel, all of us with our different tongues coming together. SIAC has been about sharing enthusiasm touching hearts and making a difference.

08 Jun

De – Extinction

“We are watching Lazarus arise from the dead, step by exciting step,” says the leader of the Lazarus Project team, Professor Mike Archer, of the University of New South Wales, in Sydney. This project is among the forefront of research today in trying to bring back to life creatures that have been extinct.

Though named after the biblical Lazarus of Bethany, the Lazarus Project has more to do with a species of frogs that brood their young ones in their stomach.

Gastric_brooding_frogThe gastric-brooding frog is said to have gone extinct in 1983, due to unintended human intervention. Humans carry among them a chytrid fungus, that grow rampant among frogs. The frogs having no methods of evasion from a fungus that isn’t native, died out. It is one among many species like the Mastodon (large mammoth like creatures), the Sabertooth and the dodo, that are considered to be part of what’s called the modern extinction.

The creatures that have been extinct since the last 10,000 years may still have enough information as DNA in their bodies for us to bring them back to life. This is because many of their remains are only now being thawed out of the permafrost of the Tundra or the snow peaks of the Andes. They’ve been protected from decay under the ice for all this time.

The technology required to bring back creatures from the dead is almost within our grasp. The ventures of de-extinction such as the Lazarus Project promise to repair the damage consequences of human civilization has done to the different ecosystems, but it also poses moral questions: should we be doing this? Is this “playing God”?

Mike Archer as well as many other scientists around the world argue that we have been interfering too much by pushing creatures beyond extinction with deforestation, overfishing, and non sustainable growth. “We should feel obliged to try and bringing back at least the creatures, whose extinction are we are directly responsible for.”

Creatures have been going extinct even before the dawn of man and isn’t this how natural selection works? Well, mass extinctions like that during the Cretaceous-Tertiary extinction that caused the dinosaur extinction have occurred five times before. An extinction period is classified as the periods in history where more number of creatures were going extinct as opposed to the number of new species coming up. What’s odd about the sixth extinction is that it’s the worst we’ve seen as a planet so far and the primary cause of that is human intervention. The last time there was an extinction phase, the ecosystem took 10 million years to stabilize again. Maybe we should try and prevent this instability from developing.

One of more interesting questions that scientists have faced is: Would we value the life of a species if we knew we were capable of bringing them back from beyond the veil of extinction? It was a refreshing insight to the problem at hand but, “It is far cheaper to conserve an already existing creature as opposed to bringing it back from extinction” said Stewart Brand, the author of the Whole Earth Catalog. Stewart Brand and his wife Ryan Phelan started an initiative called Revive and Restore, a project within The Long Now Foundation, with a mission to provide deep ecological enrichment through extinct species revival. Their hope is to be prepared. Even If an organism were to be brought back to life, enormous efforts would have to be taken to ensure life conditions would facilitate its continuous existence and also help to repopulate it further. if scientists were to bring an organism back.

This is a far more difficult a task than it appears to be. Sometimes ecosystems move on without the organism and upsetting the new ecosystem is what scientists are worried about the most. On the other hand some of these ecosystems are still currently at decline because of a missing creature.

A phenomenon called the “ Trophic Cascade” seems to govern over ecosystems, utilizing predators and other creatures at the top of the food chain as conservers. The Tasmanian Devil’s AUSTRALIA-SCIENCE-ANIMAL-DNAdecline would have been controlled had the Thylacine still been around. Tasmanian Devils have a communicable cancer that infected only it’s kind, like only seen otherwise in dogs. The Thylacine was the prime predator in Tasmania and fed constantly off on the Tasmanian Devil populations and also herbivores. The number of Tasmanian Devils that infected each other were kept in check, thus preventing the spread of the disease.

Another incidence of “Trophic Cascade” can be seen in the example of how Yellowstone National Park decided to reintroduce wolves. Since the wolves were reintroduced, the deer and the elk have grown stronger as they run from the wolves. Grasses grow taller between migrations periods. Coyote numbers that were rampant here are also shrinking. This allows more birds like the Eagle and the Osprey more food to come back for. The endangered grizzly bears successfully steal wolf kills more often than not, thus having more food to feed their cubs.

Other times, habitats the resurrected species once lived in, does not exist. The Woolly Mammoth used to live in the Grasslands of Northern Eurasia. A cold desert, the Tundra, came about when there were no more mammoths around to till and fertilize the soil as packs grazed from region to region in the search for food within this area. Sergey Zimov, A Russian ecologist has been attempting with many other ecologists to recreate vegetation and fertile land in barren land like the Tundra. Zimov feels confident that mammoths could find a home much like they had before here at ‘Pleistocene Park’ in the Tundra. He says populating it with the mammoths would only accelerate that process.

Lets say we have the ability to bring a creature back from extinction. This would be baby clone of that extinct animal with no parents. That leaves no one to teach it where to find food, where to migrate to when the seasons change or about brooding. Luckily for us, most of these instincts are innate to an animal. However they do for a lot of reasons need a substitute teacher. Identifying creatures that would help teach animals would be another challenge entirely.

October 23 , 2012 marked the first closed session meet for scientists from all walks of biology came together at National Geographic DC to discuss, “De-extinction”. Stewart Brand in his report December, 2012 states the following as thedeextinctiongrou-931x1024

  • De-extinction is exciting, moving forward, and will eventually be tried.

  • It’s unlikely to happen very soon; we have time to do it right.

  • Research on the enabling technologies should be encouraged, coordinated, and funded.

  • Mutually beneficial linkages with other on-going endeavors (e.g., endangered species recovery, ecosystem restoration, and ex situ bio-banks) should be built.

  • Priority-setting for targets and outcomes is essential “before the train leaves the station” and our discussions here have advanced the thought process.

  • De-extinction is certain to be controversial for some.

  • To deal with anticipated obstacles there should be a pro-active lead-up to the day when de-extinction is attempted (i.e., building trust and knowledge):

  • well-planned dialogue with key “stakeholders” (private initiatives, interest groups, regulators, etc.)

  • regular, open conferences/symposia reporting on progress and providing a forum for serious dialogue

  • This level of strategic planning requires considerable organizational capacity.

The San Diego Zoo, in an initiative to create a Noah’s Arch of genomic data has started an initiative called “Genome 10K” for it’s Frozen Zoo. This aims at cataloging the full genome data of 10,000 vertebrate species—approximately one for every genus. What this gives us is a repository of genomic data that we can keep alive indefinitely. This repository also allows us to breakdown, analyze and use the genetic material to make up for all the patches of DNA that’s missing as a result of natural decay of cells for revival.

Alberto Fernández – Arias in an epic, brave attempt tried to bring the Pyrenean Ibex back in 2003, 13 years after extinction. Respiratory problems are common in cloning procedures and the Ibex developed an extra lung as dense as a liver. The Ibex died but a mere 10 mins after it was born. The theory was proven. Animals can be brought back, but the process isn’t entirely kink free yet.

The National Geographic team including DNA Direct and the Smithsonian are working on creating the passenger pigeon and after that the carolina parakeet. The genome for the passenger pigeon is being stitched together from the millions of remains of genetic material they have, filling up the spaces with that of a rock pigeon.

Michael Archer, leader of the ‘Lazarus Project’, who is working on the gastric brooding frog is stuck with a frog embryo but cannot seem to get the frog to the tadpole stage, yet. He is however optimistic about his research and talks about being able to bring it back very soon. After working on the amphibian, he hopes to move onto a marsupial mammal, the Thylacine.

Development in this research goes from lower in the evolutionary chain like amphibians to higher up, like mammals or/and from smaller creatures to eventually the ones that get more attention like the larger animals. The challenge of bringing back the mammoth is more than the gastro-breeding frog for many reasons from larger DNA genomes to longer Gestation periods.

Mammoths still do however stand a higher chance of being de-extincted thanks to the antifreeze protein in their blood which was among the first things that attracted scientists to mammoth studies.

The Russians, Koreans, Japanese and the Chinese have formed the North Eastern Genomic Alliance for a parallel in De-extinction studies having discovered within the melting perma-frost at the norther Tundra, more mammoth remains in the past 5 years than ever before. The quest for viable cells for cloning has begun. The deal was signed by Vasily Vasiliev, vice rector of North-Eastern Federal University of the Sakha Republic, and cloning pioneer Hwang Woo-Suk of South Korea’s Sooam Biotech Research Foundation

Sooam said it would launch research this year if the Russian university can ship the remains. The Beijing Genomics Institute will also take part in the project.

The South Korean foundation said it would transfer technology to the Russian university, which has already been involved in joint research with Japanese scientists to bring a mammoth back to life.

Within a few short years, we will have the capacity to reverse the damage we have done, giving back to the environment in more ways than we have been able to. It will still take a while before we see a herd of wooly mammoths walking the planet again. But wouldn’t it be nicer to show your children creatures you have always dreamt of seeing?

* * * * *

– Amit Fenn

02 Mar

Surrogate Humans in Apes or Pigs

Foetus Da VinciIt is possible to implant a human fertilized egg into an ape and have them bear the child and research is being done to stretch it to even in a pig. However It hasn’t been researched upon enough and human cloning (which is what this falls under) will not happen for a long while.
There is some research that’s being done in that field. It started with exchanging Big Cats’ mothers/wombs and that’s the last I had studied of them.Research has now gone as far as dogs giving birth to tigers and so on. The technology is being stretched, hurdles understood and the gap is being bridged.

Research is being headed by 2 fronts.
1)Embryologists(developmental biologists), stem cell researchers and geneticists that combine together to bring extinct animals back to life. (More novel)
2) Supporting them, are the guys who want to protect already existing but endangered species of animals. (Easier and more responsible)

But this research cannot and will not reach Humans ANYTIME soon. When it reaches, lets be sure of two things again. 1.) We’d already have mastered the art of surrogate. 2.) We would not know of the consequences.

Next Phase in Genetics and How that will influence the research:
Natural Selection and gregor mendel’s studies are the first important pieces of genetic research happened in 1850s-1860s. Epigenetics is a phrase coined in the 1940s That says that Genetics doesn’t explain enough. In 1970s work on classical genetics lead to breakthroughs in using the information we understood to begin using it in our world and the genetic revolution begins from then on.

Epigenetic research has only been worked on since the 1990s and became a little more important after the Human Genome project got over (this was an international project on deciphering all the genetic information humans had in their cells) in 2003.
This new branch of genetics than the classical Mendelian and Darwinist evolution. It deals with Lamarck’s evolution though he doesn’t refer to it directly (he didn’t know enough). The Ultimate question being: What influences an organism: Nature vs Nurture.
Epigenetic Revolution is magnitudes larger than the genetic revolution.
Epigenetics is the study of what exists outside genetic information that controls the way cells grow and divide. Why is it that though they have the same genetic information, a neuron looks so different from an intestinal cell. We often can’t even say that they are from the same species let alone if they are from the same organism by just looking at it under a microscope.
Some Genes are switched on and some switched off, when a fertilized egg becomes more than just a clump of cells that look alike. At this stage these cells are called [embryonic]stem cells. They have different genetic information in them from a certain stage on. This switching on and off happens because of the environment of the cell (its neighboring cells, space, fluids etc)
The most impact that Epigenetics have, time wise, is on a developing egg and less major influences until a human is 4-5 years old. Heaviest impact of Epigenetics will be on the cognition as neural network development is a very fragile process, but at the scale directly impactable by epigenetics.

Nature Vs Nurture:
If we change the environment they grow up in (earlier suited for an ape or a Pig) to epigenetically influence development of man, we will change the way they think the way they feel etc. If we continue to breed such people with each other.

It will lead to mutations in regions other than what humans are used to. Eventually leading to new organisms. We can expect behavioral changes to be subtle on the outside but stronger from within. Let me show you an example: Dogs, when you look at them directly into their eyes, usually behave first with Love. Cat, when you look at them directly into their eyes, usually behave as if you are threatening them. This is because a dog is a pack animal and a Cat a solitary one. I’d expect similar changes with Lions vs Tigers. (which is why the research of the dogs giving birth to tigers is an interesting experiment for me)

So MAYBE the human that is born out of an ape will behave with more of the social structures that that particular ape species have. And Humans born out of Pigs would be too far for me to imagine (It would be interesting to know of their social structures).

Maybe the way the organism perceive the world around them change with their biology. I’ll allow these video to capture your imagination better than this text would:

http://www.youtube.com/watch?v=XbZ9xJUyIWY

http://www.youtube.com/watch?v=6hYaT4gvjNc

So we can’t go all the way to the Shrimp eyes that the video mentions but maybe to dog eyes or so. ( closer the animal is to humans more likeliness of the scale of mutation)
How will Humans deal with this MASSIVE hurdle and the inability for them to let this mingling happen:
When we understand the value of epigenetics (and most of us don’t yet) we will do our very best to avoid this kind of influence into the fertilized egg.

This might happen in CRAZY ways that we cannot predict yet from a new embryonic sac to, altering the composition of the amniotic fluid to the embryo with drugs or bypass-amniotic fluid. Again.. we cannot predict how they might try to stop it.