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This artist’s impression shows how Mars may have looked about four billion years ago. The young planet Mars would have had enough water to cover its entire surface in a liquid layer about 140 metres deep, but it is more likely that the liquid would have pooled to form an ocean occupying almost half of Mars’s northern hemisphere, and in some regions reaching depths greater than 1.6 kilometres.

Credit:
ESO/M. Kornmesser

Real Martians: How to Protect Astronauts from Space Radiation on Mars

On Aug. 7, 1972, in the heart of the Apollo era, an enormous solar flare exploded from the sun’s atmosphere. Along with a gigantic burst of light in nearly all wavelengths, this event accelerated a wave of energetic particles. Mostly protons, with a few electrons and heavier elements mixed in, this wash of quick-moving particles would have been dangerous to anyone outside Earth’s protective magnetic bubble. Luckily, the Apollo 16 crew had returned to Earth just five months earlier, narrowly escaping this powerful event.

In the early days of human space flight, scientists were only just beginning to understand how events on the sun could affect space, and in turn how that radiation could affect humans and technology. Today, as a result of extensive space radiation research, we have a much better understanding of our space environment, its effects, and the best ways to protect astronauts—all crucial parts of NASA’s mission to send humans to Mars.

“The Martian” film highlights the radiation dangers that could occur on a round trip to Mars. While the mission in the film is fictional, NASA has already started working on the technology to enable an actual trip to Mars in the 2030s. In the film, the astronauts’ habitat on Mars shields them from radiation, and indeed, radiation shielding will be a crucial technology for the voyage. From better shielding to advanced biomedical countermeasures, NASA currently studies how to protect astronauts and electronics from radiation – efforts that will have to be incorporated into every aspect of Mars mission planning, from spacecraft and habitat design to spacewalk protocols.

This artist’s impression shows how Mars may have looked about four billion years ago. The young planet Mars would have had enough water to cover its entire surface in a liquid layer about 140 metres deep, but it is more likely that the liquid would have pooled to form an ocean occupying almost half of Mars’s northern hemisphere, and in some regions reaching depths greater than 1.6 kilometres. Credit: ESO/M. Kornmesser
This artist’s impression shows how Mars may have looked about four billion years ago. The young planet Mars would have had enough water to cover its entire surface in a liquid layer about 140 metres deep, but it is more likely that the liquid would have pooled to form an ocean occupying almost half of Mars’s northern hemisphere, and in some regions reaching depths greater than 1.6 kilometres.
Credit:
ESO/M. Kornmesser

“The space radiation environment will be a critical consideration for everything in the astronauts’ daily lives, both on the journeys between Earth and Mars and on the surface,” said Ruthan Lewis, an architect and engineer with the human spaceflight program at NASA’s Goddard Space Flight Center in Greenbelt, Maryland. “You’re constantly being bombarded by some amount of radiation.”

Radiation, at its most basic, is simply waves or sub-atomic particles that transports energy to another entity – whether it is an astronaut or spacecraft component. The main concern in space is particle radiation. Energetic particles can be dangerous to humans because they pass right through the skin, depositing energy and damaging cells or DNA along the way. This damage can mean an increased risk for cancer later in life or, at its worst, acute radiation sickness during the mission if the dose of energetic particles is large enough.

Fortunately for us, Earth’s natural protections block all but the most energetic of these particles from reaching the surface. A huge magnetic bubble, called the magnetosphere, which deflects the vast majority of these particles, protects our planet. And our atmosphere subsequently absorbs the majority of particles that do make it through this bubble. Importantly, since the International Space Station (ISS) is in low-Earth orbit within the magnetosphere, it also provides a large measure of protection for our astronauts.

“We have instruments that measure the radiation environment inside the ISS, where the crew are, and even outside the station,” said Kerry Lee, a scientist at NASA’s Johnson Space Center in Houston.

This ISS crew monitoring also includes tracking of the short-term and lifetime radiation doses for each astronaut to assess the risk for radiation-related diseases. Although NASA has conservative radiation limits greater than allowed radiation workers on Earth, the astronauts are able to stay well under NASA’s limit while living and working on the ISS, within Earth’s magnetosphere.

But a journey to Mars requires astronauts to move out much further, beyond the protection of Earth’s magnetic bubble.

“There’s a lot of good science to be done on Mars, but a trip to interplanetary space carries more radiation risk than working in low-Earth orbit,” said Jonathan Pellish, a space radiation engineer at Goddard.

A human mission to Mars means sending astronauts into interplanetary space for a minimum of a year, even with a very short stay on the Red Planet. Nearly all of that time, they will be outside the magnetosphere, exposed to the harsh radiation environment of space. Mars has no global magnetic field to deflect energetic particles, and its atmosphere is much thinner than Earth’s, so they’ll get only minimal protection even on the surface of Mars.

 

Throughout the entire trip, astronauts must be protected from two sources of radiation. The first comes from the sun, which regularly releases a steady stream of solar particles, as well as occasional larger bursts in the wake of giant explosions, such as solar flares and coronal mass ejections, on the sun. These energetic particles are almost all protons, and, though the sun releases an unfathomably large number of them, the proton energy is low enough that they can almost all be physically shielded by the structure of the spacecraft.

 

Since solar activity strongly contributes to the deep-space radiation environment, a better understanding of the sun’s modulation of this radiation environment will allow mission planners to make better decisions for a future Mars mission. NASA currently operates a fleet of spacecraft studying the sun and the space environment throughout the solar system. Observations from this area of research, known as heliophysics, help us better understand the origin of solar eruptions and what effects these events have on the overall space radiation environment.

 

“If we know precisely what’s going on, we don’t have to be as conservative with our estimates, which gives us more flexibility when planning the mission,” said Pellish.

 

The second source of energetic particles is harder to shield. These particles come from galactic cosmic rays, often known as GCRs. They’re particles accelerated to near the speed of light that shoot into our solar system from other stars in the Milky Way or even other galaxies. Like solar particles, galactic cosmic rays are mostly protons. However, some of them are heavier elements, ranging from helium up to the heaviest elements. These more energetic particles can knock apart atoms in the material they strike, such as in the astronaut, the metal walls of a spacecraft, habitat, or vehicle, causing sub-atomic particles to shower into the structure. This secondary radiation, as it is known, can reach a dangerous level.

 

There are two ways to shield from these higher-energy particles and their secondary radiation: use a lot more mass of traditional spacecraft materials, or use more efficient shielding materials.

 

The sheer volume of material surrounding a structure would absorb the energetic particles and their associated secondary particle radiation before they could reach the astronauts. However, using sheer bulk to protect astronauts would be prohibitively expensive, since more mass means more fuel required to launch.

 

Using materials that shield more efficiently would cut down on weight and cost, but finding the right material takes research and ingenuity. NASA is currently investigating a handful of possibilities that could be used in anything from the spacecraft to the Martian habitat to space suits.

 

“The best way to stop particle radiation is by running that energetic particle into something that’s a similar size,” said Pellish. “Otherwise, it can be like you’re bouncing a tricycle off a tractor-trailer.”

 

Because protons and neutrons are similar in size, one element blocks both extremely well—hydrogen, which most commonly exists as just a single proton and an electron. Conveniently, hydrogen is the most abundant element in the universe, and makes up substantial parts of some common compounds, such as water and plastics like polyethylene. Engineers could take advantage of already-required mass by processing the astronauts’ trash into plastic-filled tiles used to bolster radiation protection. Water, already required for the crew, could be stored strategically to create a kind of radiation storm shelter in the spacecraft or habitat. However, this strategy comes with some challenges—the crew would need to use the water and then replace it with recycled water from the advanced life support systems.

 

Polyethylene, the same plastic commonly found in water bottles and grocery bags, also has potential as a candidate for radiation shielding. It is very high in hydrogen and fairly cheap to produce—however, it’s not strong enough to build a large structure, especially a spacecraft, which goes through high heat and strong forces during launch. And adding polyethylene to a metal structure would add quite a bit of mass, meaning that more fuel would be required for launch.

 

“We’ve made progress on reducing and shielding against these energetic particles, but we’re still working on finding a material that is a good shield and can act as the primary structure of the spacecraft,” said Sheila Thibeault, a materials researcher at NASA’s Langley Research Center in Hampton, Virginia.

 

One material in development at NASA has the potential to do both jobs: Hydrogenated boron nitride nanotubes—known as hydrogenated BNNTs—are tiny, nanotubes made of carbon, boron, and nitrogen, with hydrogen interspersed throughout the empty spaces left in between the tubes. Boron is also an excellent absorber secondary neutrons, making hydrogenated BNNTs an ideal shielding material.

“This material is really strong—even at high heat—meaning that it’s great for structure,” said Thibeault.

Remarkably, researchers have successfully made yarn out of BNNTs, so it’s flexible enough to be woven into the fabric of space suits, providing astronauts with significant radiation protection even while they’re performing spacewalks in transit or out on the harsh Martian surface. Though hydrogenated BNNTs are still in development and testing, they have the potential to be one of our key structural and shielding materials in spacecraft, habitats, vehicles, and space suits that will be used on Mars.

Physical shields aren’t the only option for stopping particle radiation from reaching astronauts: Scientists are also exploring the possibility of building force fields. Force fields aren’t just the realm of science fiction: Just like Earth’s magnetic field protects us from energetic particles, a relatively small, localized electric or magnetic field would—if strong enough and in the right configuration—create a protective bubble around a spacecraft or habitat. Currently, these fields would take a prohibitive amount of power and structural material to create on a large scale, so more work is needed for them to be feasible.

The risk of health effects can also be reduced in operational ways, such as having a special area of the spacecraft or Mars habitat that could be a radiation storm shelter; preparing spacewalk and research protocols to minimize time outside the more heavily-shielded spacecraft or habitat; and ensuring that astronauts can quickly return indoors in the event of a radiation storm.

Radiation risk mitigation can also be approached from the human body level. Though far off, a medication that would counteract some or all of the health effects of radiation exposure would make it much easier to plan for a safe journey to Mars and back.

“Ultimately, the solution to radiation will have to be a combination of things,” said Pellish. “Some of the solutions are technology we have already, like hydrogen-rich materials, but some of it will necessarily be cutting edge concepts that we haven’t even thought of yet.”

Longstanding problem put to rest:Proof that a 40-year-old algorithm is the best possible will come as a relief to computer scientists.

By Larry Hardesty


CAMBRIDGE, Mass. – Comparing the genomes of different species — or different members of the same species — is the basis of a great deal of modern biology. DNA sequences that are conserved across species are likely to be functionally important, while variations between members of the same species can indicate different susceptibilities to disease.

The basic algorithm for determining how much two sequences of symbols have in common — the “edit distance” between them — is now more than 40 years old. And for more than 40 years, computer science researchers have been trying to improve upon it, without much success.

At the ACM Symposium on Theory of Computing (STOC) next week, MIT researchers will report that, in all likelihood, that’s because the algorithm is as good as it gets. If a widely held assumption about computational complexity is correct, then the problem of measuring the difference between two genomes — or texts, or speech samples, or anything else that can be represented as a string of symbols — can’t be solved more efficiently.

In a sense, that’s disappointing, since a computer running the existing algorithm would take 1,000 years to exhaustively compare two human genomes. But it also means that computer scientists can stop agonizing about whether they can do better.

“This edit distance is something that I’ve been trying to get better algorithms for since I was a graduate student, in the mid-’90s,” says Piotr Indyk, a professor of computer science and engineering at MIT and a co-author of the STOC paper. “I certainly spent lots of late nights on that — without any progress whatsoever. So at least now there’s a feeling of closure. The problem can be put to sleep.”

Moreover, Indyk says, even though the paper hasn’t officially been presented yet, it’s already spawned two follow-up papers, which apply its approach to related problems. “There is a technical aspect of this paper, a certain gadget construction, that turns out to be very useful for other purposes as well,” Indyk says.

Squaring off

Edit distance is the minimum number of edits — deletions, insertions, and substitutions — required to turn one string into another. The standard algorithm for determining edit distance, known as the Wagner-Fischer algorithm, assigns each symbol of one string to a column in a giant grid and each symbol of the other string to a row. Then, starting in the upper left-hand corner and flooding diagonally across the grid, it fills in each square with the number of edits required to turn the string ending with the corresponding column into the string ending with the corresponding row.

Computer scientists measure algorithmic efficiency as computation time relative to the number of elements the algorithm manipulates. Since the Wagner-Fischer algorithm has to fill in every square of its grid, its running time is proportional to the product of the lengths of the two strings it’s considering. Double the lengths of the strings, and the running time quadruples. In computer parlance, the algorithm runs in quadratic time.

That may not sound terribly efficient, but quadratic time is much better than exponential time, which means that running time is proportional to 2N, where N is the number of elements the algorithm manipulates. If on some machine a quadratic-time algorithm took, say, a hundredth of a second to process 100 elements, an exponential-time algorithm would take about 100 quintillion years.

Theoretical computer science is particularly concerned with a class of problems known as NP-complete. Most researchers believe that NP-complete problems take exponential time to solve, but no one’s been able to prove it. In their STOC paper, Indyk and his student Artūrs Bačkurs demonstrate that if it’s possible to solve the edit-distance problem in less-than-quadratic time, then it’s possible to solve an NP-complete problem in less-than-exponential time. Most researchers in the computational-complexity community will take that as strong evidence that no subquadratic solution to the edit-distance problem exists.

Can’t get no satisfaction

The core NP-complete problem is known as the “satisfiability problem”: Given a host of logical constraints, is it possible to satisfy them all? For instance, say you’re throwing a dinner party, and you’re trying to decide whom to invite. You may face a number of constraints: Either Alice or Bob will have to stay home with the kids, so they can’t both come; if you invite Cindy and Dave, you’ll have to invite the rest of the book club, or they’ll know they were excluded; Ellen will bring either her husband, Fred, or her lover, George, but not both; and so on. Is there an invitation list that meets all those constraints?

In Indyk and Bačkurs’ proof, they propose that, faced with a satisfiability problem, you split the variables into two groups of roughly equivalent size: Alice, Bob, and Cindy go into one, but Walt, Yvonne, and Zack go into the other. Then, for each group, you solve for all the pertinent constraints. This could be a massively complex calculation, but not nearly as complex as solving for the group as a whole. If, for instance, Alice has a restraining order out on Zack, it doesn’t matter, because they fall in separate subgroups: It’s a constraint that doesn’t have to be met.

At this point, the problem of reconciling the solutions for the two subgroups — factoring in constraints like Alice’s restraining order — becomes a version of the edit-distance problem. And if it were possible to solve the edit-distance problem in subquadratic time, it would be possible to solve the satisfiability problem in subexponential time.

Source: MIT News Office

Ant-Man possible? Scientists shrink ants to study mechanisms that control DNA expression

By shrinking ants to sizes smaller than exist in nature, biologists present a useful model for understanding how environmental factors can influence DNA expression to create a range of outcomes.

This may not be exactly what the Marvel’s Ant-Man story has but still close enough to be amazing! 

BY BJORN CAREY


In the pages of Marvel comic books, Ant-Man manipulates fictional subatomic particles in order to shrink and fight crime as one of Earth’s mightiest heroes.

In real life, a team of biologists has now achieved similar shrinking results by manipulating ants’ DNA. The work won’t produce any superpowers, but it presents a useful model for understanding how environmental factors can influence DNA expression to create a range of outcomes in a population.

The work is published online in the journal Nature Communications. Sebastian Alvarado, a postdoctoral fellow at Stanford, conducted the research as a graduate student at McGill University, working alongside fellow graduate student Rajendhran Rajakumar, and professors Ehab Abouheif and Moshe Szyf, all of McGill.

 

Video : Stanford researcher explains the science behind Ant-Man

The experiment was designed as a means to study variation in quantitative traits. These are individual qualities, such as height or body weight, that can naturally vary across a defined range in a population. This variation is usually driven by the degree that environmental or other factors influence the expression of a particular gene, which makes ants an excellent test model.

In an ant colony, queens, workers and soldiers share similar genetics. But early in ant development, social, nutritional and chemical cues cause some genes to be more active, ultimately creating a wide range of body sizes, each specialized to a different task in the colony.

Many of these changes are controlled by DNA methylation, a process in which molecules are added to sections of DNA sequences. These additions affect how the DNA is interpreted and expressed, thus influencing an organism’s development or behavior.

“A lot of growth and development and sizing mechanisms that exist across the animal kingdom are found to be regulated by the same DNA methylation processes,” Alvarado said.

In the experiment, Alvarado and his colleagues at McGill exposed ant larvae to drugs that either increased or decreased the amount of DNA methylation. In doing so, they created ants that were larger within a caste and even significantly smaller than what exists in a natural population.

They then traced this size change to a specific growth factor gene, and found that across the population, varying degrees of DNA methylation to that gene directly corresponded to body size. A 20 percent modification in DNA methylation yielded a 20 percent change in body size, for example.

“This helps explain at a molecular level how continuums exist between two very discrete variables,” said Alvarado, who is now a member of biology Professor Russell Fernald’s lab at Stanford. “We can now look at diversity within a population by considering what expressions exist in between these variables and the actual molecular mechanism that controls that difference.”

Drawing a stronger connection between how environment and genetic factors influence DNA expression, Alvarado said, could have payoff in mapping the genetic basis of diseases and understanding evolutionary changes.

Source: Stanford News


 

New way to turn genes on

Technique allows rapid, large-scale studies of gene function.

By Anne Trafton


CAMBRIDGE, MA — Using a gene-editing system originally developed to delete specific genes, MIT researchers have now shown that they can reliably turn on any gene of their choosing in living cells.

This new application for the CRISPR/Cas9 gene-editing system should allow scientists to more easily determine the function of individual genes, according to Feng Zhang, the W.M. Keck Career Development Professor in Biomedical Engineering in MIT’s Departments of Brain and Cognitive Sciences and Biological Engineering, and a member of the Broad Institute and MIT’s McGovern Institute for Brain Research.

This approach also enables rapid functional screens of the entire genome, allowing scientists to identify genes involved in particular diseases. In a study published in the Dec. 10 online edition of Nature, Zhang and colleagues identified several genes that help melanoma cells become resistant to a cancer drug.

Silvana Konermann, a graduate student in Zhang’s lab, and Mark Brigham, a McGovern Institute postdoc, are the paper’s lead authors.

A new function for CRISPR

The CRISPR system relies on cellular machinery that bacteria use to defend themselves from viral infection. Researchers have previously harnessed this cellular system to create gene-editing complexes that include a DNA-cutting enzyme called Cas9 bound to a short RNA guide strand that is programmed to bind to a specific genome sequence, telling Cas9 where to make its cut.

In the past two years, scientists have developed Cas9 as a tool for turning genes off or replacing them with a different version. In the new study, Zhang and colleagues engineered the Cas9 system to turn genes on, rather than knock them out.

Scientists have tried to do this before using proteins that are individually engineered to target DNA at specific sites. However, these proteins are  difficult to work with. “If you use the older generation of tools, getting the technology to do what you actually want is a project on its own,” Konermann says. “It takes a lot of time and is also quite expensive.”

There have also been attempts to use CRISPR to turn on genes by inactivating the part of the Cas9 enzyme that cuts DNA and linking Cas9 to pieces of proteins called activation domains. These domains recruit the cellular machinery necessary to begin reading copying RNA from DNA, a process known as transcription.

However, these efforts have been unable to consistently turn on gene transcription. Zhang and his colleagues, Osamu Nureki and Hiroshi Nishimasu at the University of Tokyo, decided to overhaul the CRISPR-Cas9 system based on an analysis they published earlier this year of the structure formed when Cas9 binds to the guide RNA and its target DNA. “Based on knowing its 3-D shape, we can think about how to rationally improve the system,” Zhang says.

In previous efforts, scientists had tried to attach the activation domains to either end of the Cas9 protein, with limited success. From their structural studies, the MIT team realized that two small loops of the RNA guide poke out from the Cas9 complex and could be better points of attachment because they allow the activation domains to have more flexibility in recruiting transcription machinery.

Using their revamped system, the researchers activated about a dozen genes that had proven difficult or impossible to turn on using the previous generation of Cas9 activators. Each gene showed at least a twofold boost in transcription, and for many genes, the researchers found multiple orders of magnitude increase in activation.

Genome-scale activation screening

Once the researchers had shown that the system was effective at activating genes, they created a library of 70,290 guide RNAs targeting all of the more than 20,000 genes in the human genome.

They screened this library to identify genes that confer resistance to a melanoma drug called PLX-4720. This drug worksDrugs of this type work well in patients whose melanoma cells have a mutation in the BRAF gene, but cancer cells that survive the treatment can grow into new tumors, allowing the cancer to recur.

To discover the genes that help cells become resistant, the researchers delivered CRISPR components to a large population of melanoma cells grown in the lab, with each cell receiving a different guide RNA targeting a different gene. After treating the cells with PLX-4720, they identified several genes that helped the cells to survive — some previously known to be involved in drug resistance, as well as several novel targets.

Studies like this could help researchers discover new cancer drugs that prevent tumors from becoming resistant.

“You could start with a drug that targets the mutated BRAF along with combination therapy that targets genes that allow the cell to survive. If you target both of them at the same time, you could likely prevent the cells from developing resistance mechanisms that enable further growth despite drug treatment,” Konermann says.

Scientists have tried to do large-scale screens like this by delivering single genes carried by viruses, but that does not work with all genes.

Zhang’s lab also plans to use this technique to screen for genes that, when activated, could correct the effects of autism or neurodegenerative diseases such as Alzheimer’s. He also plans to make the necessary reagents available to academic labs that want to use them, through the Addgene repository.

The research was funded by the National Institute of Mental Health; the National Institute of Neurological Disorders and Stroke; the Keck, Searle Scholars, Klingenstein, Vallee, and Simons foundations; and Bob Metcalfe.

Sourse: MIT News