New Mechanism of Regulating Gene Expression Discovered

A few months ago, much ado was made about results from the ENCODE project on the human genome, publicized as having made the discovery that 80% of the human genome has a biochemical function. While this is true (with ‘biochemical function’ being defined loosely and broadly), we don’t yet know how or why most of the long stretch of DNA in our cells is important. ‘Genes’ as we know them make up less than 2% of the total DNA. What purpose does the rest of it serve?

What Purpose does “Junk DNA” Serve?

The ENCODE project suggested that the rest of the genome had a strong regulatory potential. How do our cells control when to turn on certain genes, when to ramp up production of one protein and when to slow down? A lot of these regulatory mechanisms remain unknown. A team of researchers at Wistar Institute have now discovered one additional mechanism of regulation.

Before we move on, let’s briefly review how genes function. ‘Genes’ are essentially regions of the genome which are processed into intermediate molecules called ‘RNA’, also linear strings. These RNA strings are further processed to yield the protein that performs the gene’s function. Think of the gene as a ‘recipe’ for a protein, with the RNA molecule being the unfinished product halfway along the recipe. There are, however, some regions of the genome which are processed to form RNAs, but do not form proteins. They often have regulatory functions.

ncRNA-a (the region of the genome on upper segment of the loop) helps the mediator protein complex to gain a foothold on the right region, so that the gene (shown by ‘mRNA’ on the lower segment of the loop) can be transcribed. [Image Credit: Nature Publishing Group]

Long Non-Coding RNAs Regulate Gene Expression

Moving back to the research team, they had previously discovered that a class of these ‘non-coding RNAs’, which they have termed ‘ncRNA-a’, serve to activate processing of their neighbouring genes. But how do they do this? There are certain proteins called mediators which facilitate the processing of genes to RNA. They have now discovered that ncRNA-a helps these mediator proteins bind to these genes at the right place. To determine this, the team removed proteins known to be involved in gene processing (called transcription) one by one, and looked for changes in ncRNA-a mediated activation. And voilà, components of the mediator complex came up immediately. They also found that the chromosome forms a loop between the ncRNA-a locus and the gene locus, for the mediator complex to be able to gain a stronghold at the gene locus using the ncRNA-a as a base.

Why is this result important? It gives us a better idea of the factors controlling gene expression. And as importantly, it helps us understand our DNA just a little better. You can read about this research here.

Poachers 11100: Conservation 0

Shocking figures on elephant conservation have just been released by the Wildlife Conservation Society (WCS). The Minkebe National Park in Gabon has lost as many as 11,100 elephants to the ivory trade in the last 9 years.

Rampant Elephant Poaching in Gabon

Gabon is home to more than half of Africa’s elephants, and elephant poaching in this region was believed to be less than in other regions of Africa, where 31000 elephants are estimated to have been lost due to poaching. However, there has been increased human activity seen in this National Park, with there being around 5000 miners, poachers and arms and drugs dealers on its premises. Authorities believe that 50-100 elephants could be killed everyday.

Image Source: Wikimedia commons
Gabon’s elephant population is estimated to be 40,000. This number may not be safe. [Image Source: Wikimedia commons]

Increasing Demand for Ivory

According to a previous report by the CNN, there is an increased demand for ivory which can be attributed to economic growth in Asia, where ivory is valued for ceremonial and cultural purposes. The price of ivory has reached $1000 per pound. The statistics released highlight the extent of the threat these pose to conservation.

Authorities Respond

These statistics are dramatic enough to have evoked reactions from the Gabonese government. The president has vowed to introduce further legislation to dissuade poachers, including longer prison terms. He also called for an integrated effort to meet this problem. He was echoed by the president and CEO of WCS. “This sad news from Gabon confirms that without a global commitment, great elephant populations will soon become a thing of the past,” said WCS President and CEO Cristián Samper. “We believe that elephants can still be saved – but only if nations greatly increase their efforts to stop poaching while eliminating the illegal ivory trade through better enforcement and reduced demand.”

The surveys were conducted by WCS, WWF and Gabon’s National Parks Agency. This report was sourced from a press release by WCF, which you can read here.

How Does Our Brain Create Fear?

Why do we feel fear? For years, a part of the brain called the amygdala has been implicated in this emotional response. This region links memories with emotional responses, one of which might be fear. A patient (known as S.M.) with dysfunctional amygdalae on both sides of her brain has been known to show no fear in response to various fear-inducing stimuli, including life-threatening traumatic events.

Everyday Gas Induces Fear in the Brain

Another stimulus that is known to evoke fear is carbon dioxide. Inhaling this gas turns on a protein which in turn plays a role in fear and anxiety (how this protein works in inducing fear remains unknown). How would patients with damaged amygdalae react to this stimulus? A team of researchers at the University of Iowa tried to find out.

fear center in the brain
The first image is a scan from a normal patient and the next three are from patients with damaged amgydalae. The area marked in red shows the lesions present in their brains. [Image Source: Iowa Neurological Patient Registry at the University of Iowa]

‘Fearless’ Patients Show Fear

To their surprise, they found that the 3 people with lesion in their amygdalae (let’s call them patients) showed a greater degree of panic than a group of patients with normal amygdalae. The patients described having experienced emotions they had never felt before, with their descriptions residing well under the category of ‘fear’. Clearly, these results show that the amygdala is not an absolute necessity for fear. However, anticipatory responses to the inhalation, such as an increased heart rate before inhalation, were shown to be significantly increased in controls when compared to patients.

These results led the authors to believe that the carbon dioxide activated a previously unused pathway in patients with damaged amygdalae. One possibility is that most stimuli that normally induce fear are external—perceived visually or auditorily—, whereas inhalation of carbon dioxide represents a physiological, internal, change that does not need processing by the amygdala to generate fear. Another conclusion that the authors came to was that the amygdala might, to some degree, inhibit fear, since the degree of panic attacks was milder in the control group.

Fear is an important survival mechanism, and this experiment gives important clues to its origin. You can read about this research here.

Novel Method To Invade Cells

One of the current paradigms of molecular biology research is to study cells by manipulating them. Insert a piece of DNA and see what changes. Add a protein and see if the cell can now become cancerous. Inactivate a protein and see if a diseased cell becomes normal.

One of the trickiest steps in such processes is often getting the foreign substance inside a cell. Living cells have membranes designed to keep out foreign substances and to absorb just what the cell wants. How do we let particularly large molecules in?

Infiltrating the Cell’s Walls

Pieces of DNA are usually inserted into a longer fragment of DNA called a vector (to keep the DNA stable). The cell is then shocked to jolt the proteins in its membrane and make it temporarily porous. This method can work for small molecules, and another method is the chemical disruption of the membrane temporarily. The problem with these methods is that they change some properties of the cell, and the goal of such experiments is to observe changes in the cell that is ONLY because of the inserted molecule, and not due to other factors (such that the result of a shock might lead to). Another method is to deliver the molecule inside nanoparticles which can then enter the cell, but the nanoparticle is often captured by an organelle of the cell, and the molecule is then not released. The cell’s membrane also allows certain protein to pass through it—think of it like a gatekeeper, letting proteins of certain charges and small enough sizes go through while keeping out the others.

This image gives the workflow of the microfluidics device. Figure A shows cells flowing through a tube with a constriction. After being squeezed, these cells are now have the delivery material inside them. [Image Credit: Sharei et al; PNAS]

Squeezing Cells to Make Them Yield

A general method of insertion would thus be a useful tool in research. Researchers at MIT have come up with the solution mothers use when their children don’t eat food—they press in the child’s cheeks till their mouths open. This team has developed a microfluidics device that does something similar. Cells (and the delivery material) flow through a tubes under external pressure and are forced to pass through a tiny constriction in the tube (see figure). During this phase, the cells are compressed to such tiny sizes that their membranes ‘split’ temporarily, leaving gaps for molecules to enter.

The team used this method to generate stem cells (by inserting the necessary factors into cells) and found that this method had an efficiency 10 to 100 times greater than other existing methods. Their next step is to use this for therapeutic purposes, wherein a patient’s cells could be taken out of his body, injected with the necessary DNA/protein, and re-injected into his/her body.

You can read about this research here.

Deadly Ebola Strain Could Infect Asian Bats

Ebola is a viral disease that has been a threat for more than a decade. Detected in Africa, this virus causes a serious haemorrhagic fever and has high fatality rates. There have been indications that it is from bats that these viruses infect humans, and a new study in Bangladesh lends this further credence.

Source of the Disease

Diseases like Ebola emerge periodically in human populations, and just as suddenly, disappear following an outbreak. This patterns owes itself to the virus being ‘zoonotic’—a virus that infects humans via another organism. Zoonotic diseases are hard to eradicate because we can’t immunize animals in the wild. This is why we have effective vaccines for Measles (not zoonotic), but Ebola or the flu is always on the radar for health officials. Thus, a crucial step in studying zoonotic diseases is determining their primary hosts. One criterion for primary hosts is that the virus shouldn’t be too harmful to them. If it were, it would kill the host organism and would not be able to circulate for long periods of time, as it does. Humans are definitely not its primary hosts—each outbreak subsides soon after its origin because it is so lethal.

This innocuous virion is the cause of a deadly disease. [Image Source: wikipedia]

Ebola Virus in Bats

The organism which is the original reservoir of Ebola virus has not been known for certain, though previous studies have found a few species of bats infected with Ebola. Now, researchers have studied 276 bats in three regions of Bangladesh and identified antibodies against the Ebola virus in 4% of these, meaning that the bats have, at some point, been exposed to the Ebola virus. However, they haven’t found live virus in bats, which is the piece of evidence necessary to confirm that bats are a reservoir, i.e. a permanent ‘store’ of the virus.

What Does this Study Tell Us?

Bats harbouring antibodies for Ebola has already been found—what new information does this study yield? This study tested bats for 2 strains of the virus: the Reston strain which has been seen in animals across the world (and has not caused human disease), and the more deadly Zaire strain, which has a whopping mortality rate of around 80% and was previously seen only in Africa. Antibodies for both these strains were found by this study, which means that a Zaire Ebola infectious outbreak in Asia remains a distinct possibility. How possible? We don’t know, until we have more evidence on prevalence of the virus in its primary hosts.

This research was conducted by the EcoHealth Alliance. You can read about this study here.

Ancient Link Between India and Australia

The study of the human genome continues to yield new insights about our history. A new study on the variation seen across human populations has revealed an ancient migration from India to Australia 141 generations ago, one that hadn’t been on record.

It is accepted that human populations migrated out of Africa and subsequently colonized the world. Some previous studies have shown that a wave of migration (called the ‘southern route’ of migration) to the Australian landmass occurred around 45000 years ago, following which this population remained isolated until colonization by Europeans in the 18th Century. This study upends this conclusion.

How Does Such Genetic Analysis Work?

Before the era of airplanes and global migration, populations across the world were relatively isolated, mainly because of geographical barriers, and often because of cultural and social barriers. Thus, members of each population would only breed with other members of the same population. Over time, this lack of interbreeding, or genetic mixing between different populations, led to distinct patterns that could be seen in each population. It is by looking at similarities and differences in these that we can compare genetic data.

A Study of Global Populations

The distribution of samples used in the study. [Image Source: PNAS: doi: 10.1073/pnas.1211927110]

Researchers at the Max Planck Institute for Evolutionary Anthropology collected ‘genotype data’—genetic data only at commonly varying locations in the genome—from different populations across the world (see figure above), and looked for patterns of similarities across these populations in terms of their genetic data. Using this genetic data and known rates of genetic change, they found a genetic link between populations from Australia, New Guinea and Mamanwa (an ancient group from the Philippines). This is consistent with the ‘southern route’ theory. What was novel was a significant similarity between Indian populations and Australian populations. This indicates a pattern of gene flow from India to Australia approximately 4230 years ago, a period called the Holocene.

Genetic Link Matches Archaeological Record—Coincidence?

This is fascinating because of an archaeological factoid of this period. This represents the period when changes in tool technology, food processing and a dog native to Australia called the dingo emerged on the Australian subcontinent. Could this emergence be related to the migration occurring in the same period?

It is plausible that this wave of migration was not direct, i.e., it could have been through the region of S.E. Asia, which shares long cultural links with Australia. However, the patterns of similarity seen between the Indian and Australian populations are not seen in the South-East Asian populations which were also included in this study. This means that there was a direct migration between India and Australia.

The study of our past is a fascinating one. Genetic data is an invaluable tool in this pursuit, and provides a tangible way for mankind to trace its evolutionary past.

You can read about this research here.

Shopping for Diamonds—in Space

Astrophysicists are hypothesizing that a previously discovered planet could have a diamond interior.

This planet, called 55 Cancri e, is an exoplanet (a planet outside the solar system) that orbits a star called 55 Cancri. Its was the one of the first ‘Super-earths’ to be discovered—its mass is greater than that of earth (around 7.8 times), yet much smaller than the masses of Uranus and Neptune. Estimates of its interior composition and atmosphere had already been made from previous studies observing its transits across the star (similar to the much talked-about Venus transit earlier this year). It was estimated that this planet had a core of iron and silicates, and an envelope of supercritical water (i.e., water in a blurred state between liquid and gas).

However, these estimates were based on the assumption that the planet had an oxygen-rich interior, similar to earth. This assumption is now being challenged in a new model proposed by researchers at Yale University. The star around which the planet orbits itself has a carbon-rich interior, and 55 Cancri e is the closest planet to the star. This led to a new model that the planet could have an interior of carbon instead of oxygen, which could also lead to the observed properties of the planet.

An illustration of the planet 55 Cancri e’s interior. A molten iron core at its center, an outer layer of graphite, and an interior of diamond. [Image Credit: and Haven Giguerre]

However, based on the known temperature and pressure of 55 Cancri e, any carbon in its interior would have to exist in the form of diamond. “This is the first glimpse of a rocky world with a fundamentally different chemistry from Earth. The surface of this planet is likely covered in graphite and diamond rather than water and granite,” said Nikku Madhusudhan, who was the first author on this paper.

If this proves to be true, the phrase ‘like a diamond in the sky’, may turn out to be more than a simile. You can read about this research here and here.

Why Does a Nail on a Blackboard Make Us Cringe?

Why is the sound of nails on a blackboard (and to some of us, even the thought of it) enough to make us wince and cover our ears? Do our ears respond differently to them?

It has been previously known (by brain imaging studies) that in addition to the auditory part of our brain (the auditory cortex), the emotional center of the brain—the amygdala—is also activated by unpleasant sounds. Now how does this dual response work? How are unpleasant sounds represented in the brain? Do specific auditory signals go to the amygdala from the auditory cortex or does it receive them directly? Researchers at Newcastle University have performed a series of experiments seeking to determine precisely this.

The brain scans of 16 participants were obtained in response to a variety of pleasant (bubbling walter, a baby laughing) and unpleasant sounds (a fork scraping glass, nails against a blackboard). Based on these scans, the research team could chalk out the series of events that lead to the disturbed response exhibited upon hearing unpleasant sounds.

Why this aversion to some sounds? [Image Credit:]

The sound signals are first processed by the cortex and then transferred to the amygdala. The amygdala, upon recognizing the signal as being ‘unpleasant’, kicks in to transfer a signal back to the auditory cortex, driving it to perceive the sound as even more unpleasant. What this means is that the intense discomfort you experience when you hear an electric drill is driven by an emotional response. “It appears there is something very primitive kicking in,” says Dr Sukhbinder Kumar, the paper’s author from Newcastle University. “It’s a possible distress signal from the amygdala to the auditory cortex.”

The authors also noted that most sounds we classify as unpleasant belong to a high frequency range of the auditory spectrum, the same range in which the sound of a human screaming can be found. Perhaps our aversion to these sounds are thus evolutionary.

This study could be extended to learn more about the generality of this result. Is this specific to unpleasant sounds? What about words with negative connotations? What about words that are merely ‘negative’ but not distinctly unpleasant? The same research methodology can be extended to uncover the mechanisms by which our brain processes auditory information.

You can read about this research here.

Nobel Prize in Medicine Explained

So the Nobel Prize in Physiology and Medicine for 2012 has been announced, but what have the deserving winners done anyway? Here’s a look at the defining achievements that have cemented their place in history.

What’s the Big Deal With Stem Cells?

Sir John Gurdon from Cambridge and Dr. Shinya Yamanaka from Kyoto University have won the prize for their work on induced pluripotent stem cells (IPS), and every biologist has greeted this news with a cheer. Every cell in our body is specialized to perform its own task; that’s why your food goes into your stomach and air into your lungs. However, every cell in our body arises from one single cell. How does this division of labor occur? At some stage of development in the womb, cells undergo a process called ‘differentiation’, which is what tells the cells what functions they will be restricted to performing. What we call ‘stem cells’ are essentially undifferentiated cells, which are enormously powerful simply because they can turn into any type of tissue we want!

Sir John B Gurdon, who first proved that differentiation could be reversed. [Image Credit:]

This differentiation was thought to be one-directional. In 1962, Sir John Gurdon showed that the reverse of the ‘differentiation’ process could be achieved. Cells from a tissue like the skin could be reversed to form ‘stem cells’ that could in turn turn into any type of tissue. He took out the nucleus of an adult frog and injected it into an egg cell of a tadpole (from which the DNA-containing nucleus had been removed). This embryo then grew into a live tadpole, showing that ‘adult DNA’ really could become ‘immature’ again.

Dr. Shinya Yamanaka converted skin cells from mice into embryos that could grow into adult mice. [Image Credit: nobelprizeorg]
Dr. Shinya Yamanaka, in 2006, concocted an actual recipe for this reverse differentiation, and produced IPS cells from the skin cells of mice in this seminal paper. He identified 4 genes that could convert these skin cells into immature yet all-powerful stem cells.

These cells have huge potential in both medicine and research. Brain cells, for example, are notoriously difficult to isolate. Thanks to their discovery, we can produce IPS cells and culture brain cells instead of having to isolate them. While the direct applications to medicine are not yet on the horizon, this technology does hold promises for the future.


Mothers Carry Pieces of their Children—In Their Brain

Did you know that long after you’re born, your mother carries little parts of you in her body? This phenomenon is called ‘microchimerism’, the presence of foreign cells in a tissue or organ. Recent research has now found cells from the foetus in the most distal part of the mother’s body, the head.

Babies’ Cells Migrate Into Mothers’ Bodies

Microchimerism arises during pregnancy when fetal cells move into the mother’s body where they may persist and multiply for a long time. This phenomenon is how the complete sequence of a foetus’s DNA can be determined simply from the mother’s blood. The effects of these cells on the mother’s health, if any, aren’t known. Some hypothesize that these ‘foreign’ cells could trigger off the mother’s immune system leading to autoimmune diseases. Others hypothesize that these cells actually help in the repair of damaged tissues in the maternal body. The kidneys, lungs, liver, lymph nodes and the hearts of mothers have been found to contain their sons’ DNA. Do they also travel to the brain?

fetal DNA in mother's brain
The origins of microchimerism. It is during pregnancy that cells from the foetus enter the mother’s body and may persist for as long as a few decades. [Image Credit: Wikimedia commons]

Looking for Y Chromosomes in Female Brains

Firstly, let’s talk about why ‘son’s’ DNA is mentioned, but not daughters’ DNA lest scientists be accused of sexism. Males contain a copy of the Y chromosome while females don’t. Merely finding a piece of this chromosome in a woman would be sufficient to determine the presence of foreign cells (most likely to be her son’s). On the other hand, to look for a daughter’s DNA, scientist would have to look for very specific differences between the mother and the daughter’s genes.

Keeping this in mind, researchers at the University of Washington in Seattle tested if a particular sequence of DNA in the Y chromosome was found in the brains of women who had sons. 63% of mothers were found to contain this segment of DNA, indicating that fetal cells do, in fact, travel all the way to the brain.

The next time your mother says you’re in her heart or on her mind, you know she means it literally. You can read about this research here.