Cool Biology

Computational and molecular biology is arguably one of the areas of fastest expansion in science today. Ranging from mathematical ecology to the protein folding problem, this is an exciting area to work in.

About me:
My name is David Angeles, I am a Mexican student (currently a junior) studying Comp. Bio in Cornell University. We'll see where life takes me!
fuckyeahmolecularbiology:

Coloured scanning electron micrograph (SEM) image of influenza A virus particles. The most virulent of the three influenza types, the Influenza A virus particle consists of a core of RNA surrounded by a protein capsid and lipid envelope. Embedded in the capsid are two types of glycoprotein spike, haemagglutinin and neuraminidase, which determine the strain of the virus. 
Image Source: Science Photo Library

fuckyeahmolecularbiology:

Coloured scanning electron micrograph (SEM) image of influenza A virus particles. The most virulent of the three influenza types, the Influenza A virus particle consists of a core of RNA surrounded by a protein capsid and lipid envelope. Embedded in the capsid are two types of glycoprotein spike, haemagglutinin and neuraminidase, which determine the strain of the virus. 

Image Source: Science Photo Library

(Source: amolecularmatter, via davidaa11)

Darwin is wrong!

No, I’m not about to give a long and boring lecture on why creationism is right. If I ever do that, please tape my mouth shut to save me the embarrassment. 

However, I would like to seriously consider the possibility that Darwin was, in fact, wrong, about his theory of natural selection. Now though, what do I mean by wrong? Well, Darwin’s theory of evolution by natural selection is one of the main driving forces behind modern biology, providing powerful insights into the how’s and why’s of the complex mechanisms that organisms possess to enable them to live. So, really, the question is not whether he was wrong or not, but how wrong he was. 

In science, you can always be wrong. In fact, in science, you’re always wrong. Partially wrong, very wrong, completely wrong; it’s all wrong regardless! But there is a gradient of wrong, and people would be silly to deny it. Saying Newton was wrong when he said F=dP/dt is a true statement. Einstein showed just how wrong Newton was. The answer? Not very wrong… unless you’re going at a speed close to the speed of light, or if you’re a massive black hole, or some other case like that. Thus, although we often like to say that Einstein disproved Newton, because this is such a powerful and impacting statement, we could just as easily, and truly, say that Einstein refined Newton.

We are biologists, though, so back to biology. No more derivatives if we can avoid it. For now. Could Darwin have been wrong? Well, maybe. Why? Let’s understand a little bit more about Darwin’s postulates, and those of his followers (mainly, the great statistician Fisher). 

Darwinian postulates, in no particular order:
1) Selection acts on populations, not individual organisms.

2) Evolution  occurs during generations, an individual is no longer ‘evolving’. 

3) Constant phenotypic change is always in response to selection, not in spite of it. 

4) In order to be evolutionarily stable, phenotypic changes must be accompanied by genotypic changes (i.e., changes in the DNA code), because DNA is robust and so these changes can persist over time. Changes that are not engraved in the DNA are lost too quickly, and are therefore transient: They don’t affect evolution in the grand scheme. 

So. Can anyone spot any mistakes? Well, a few molecular biologists seem to think so. 

The 1st postulate is pretty robust. The reason for selection acting on a population is that evolution is actually a statistical theory - genotypes predispose fitness, but that doesn’t mean everyone with a specific genotype (set of alleles) has that exact fitness. Some have much lower, some have much higher fitness. 

The 2nd postulate seems to be robust as well. After all, people don’t gain any more limbs after they are born, no matter how convenient it would be to do so. However, quite recently, a field called Epigenetics has started to shake this up quite a bit. Why? Epigenetics means, literally, on top of genetics. It turns out that parts of your DNA can be turned on, or off, in response to environmental stimuli. Epigenetic phenomena regulate cellular differentiation, leading to organized body structures, and can also affect behavior, strength or other fitness-related traits. Moreover, it has been observed that epigenetically defined traits (i.e. traits that are not defined merely by your genotype) can actually be passed on to offspring! Now, why is this important? We are now talking about a kind of phenotype that is 1) heritable, 2) fitness-related, meaning that it can affect evolution. However, this phenotype is not engraved in the genetic code, rather, it is engraved in the manner the genetic code is expressed. 

So, although epigenetics seems like it might challenge Darwin, the catch is in the fact that it is not maintained in the genetic code, and so Darwin’s 4th postulate comes to the rescue: Since the phenotype is given by the methylation state of DNA, and the methylation state of DNA changes considerably often, this phenotype is not evolutionarily stable and thus doesn’t contribute to the overall evolutionary change of a species! Aha! Q.E.D. But is this true?

Evolutionary biologists love to use cross-species data, and I do too. So, if epigenetic changes do not contribute to the direction in which species evolve, why does every single higher-order eukaryote have epigenetic mechanisms? Because they increase the fitness of an organism. But, if the fitness effect is transient, wouldn’t epigenetic phenomena actually have a net fitness effect approaching 0 as time goes on? I’m actually not sure whether this line of reasoning is mathematically sound, but I think it could be (I haven’t worked the math for this out yet). If the fitness over time is 0, then selection can’t be strong enough to maintain this mechanism and it should be lost. Since many epigenetic mechanisms are actually essential for the survival of many organisms, these mechanisms must actually be under quite strong pressure. 

Finally, 3) says that selection causes a change in phenotype, but that phenotypes don’t change in spite of selection, at least at the population level. But is this true?  Hang on to your seats, I’m about to take a turn that is going to be hard to follow, but it promises too many rewards not to pursue it. 

Recently, biologists have discovered that proteins can actually be used to pass on phenotypes. Yup. Phenotypes can actually be inherited through proteins. Specifically, she’s shown proteins called prions can pass on information through generations. A prion is a protein that is misfolded into a sort of a fibrous state. You most likely know about prions if you’ve heard about Mad Cow Disease. That’s a protein that misfolded into what is called the prion conformation. It can be passed on, and can cause the subject to acquire a novel phenotype. Now, this caused a lot of surprise in the biological community, because, although the phenotype in this case is not a good one (Mad Cow Disease phenotype), it doesn’t require genetic information to be expressed. However, most evolutionary biologists considered it a fluke, and disregarded it because the phenotype associated with prions seemed to be always highly negative.

Even more recently, however, scientists have shown that, at least for yeast, prions can actually be beneficial. In fact, they found that in many yeast strains, prions are actually necessary to survive! 

Moreover, yeast populations continuously “bet” against the environment, with a fraction of the population maintaining the prion form of a protein, and a fraction maintaining the native form. This “bet-hedging” is stochastic, but it helps yeast protect against switching in environment. When the environment switches to a state that requires the prion conformation, not all the yeast colony dies. Likewise, if the environment now switches back to a state that require the native form of the protein, the fraction of the yeast colony that randomly switched back to the native form in the previous environment (to its detriment) can now survive and thrive in the novel environment. 

Complaints against prions are still the same as for epigenetic mechanisms, though: They aren’t permanent enough. However, genomic analyses have begun to find that specific amino acids that make prion conformations more likely appear to actually have been selected for in yeast, showing that prions could be permanent enough to yield a non-zero fitness effect. 

So, is Darwin wrong? You tell me. 

fuckyeahmolecularbiology:

Meet The Neurosphere
A neurosphere is a system composed of free-floating clusters of neural stem cells. Because stem cells cannot be studied in vivo, neurospheres provide a method of investigating neural precursor cells in vitro. To grow a neurosphere, putative neural stem cells are suspended in a medium lacking adherent substrates but containing necessary growth factors, like epidermal growth factor and fibroblast growth factor. This allows the neural cells to form characteristic 3D spheres. 
The clinical applications of neurospheres are still in their infancy, but they have the potential to help treat many diseases. Transplanted neural stem cells are not only able to cross the blood-brain barrier and integrate themselves into the host’s brain without disrupting normal function - they are also incredibly versatile, and have been shown to proliferate and differentiate in various other tissues of the body when transplanted. Researchers are currently exploring the use of neural stem cells obtained from neurospheres to aid in the growth of inner ear neurons and hair cells; the hope is that these cells may be able to restore auditory function in hearing-impaired patients.
The image above is of a neurosphere from Vanderbilt University’s Department of Molecular and Cell Biology.

fuckyeahmolecularbiology:

Meet The Neurosphere

A neurosphere is a system composed of free-floating clusters of neural stem cells. Because stem cells cannot be studied in vivo, neurospheres provide a method of investigating neural precursor cells in vitro. To grow a neurosphere, putative neural stem cells are suspended in a medium lacking adherent substrates but containing necessary growth factors, like epidermal growth factor and fibroblast growth factor. This allows the neural cells to form characteristic 3D spheres. 

The clinical applications of neurospheres are still in their infancy, but they have the potential to help treat many diseases. Transplanted neural stem cells are not only able to cross the blood-brain barrier and integrate themselves into the host’s brain without disrupting normal function - they are also incredibly versatile, and have been shown to proliferate and differentiate in various other tissues of the body when transplanted. Researchers are currently exploring the use of neural stem cells obtained from neurospheres to aid in the growth of inner ear neurons and hair cells; the hope is that these cells may be able to restore auditory function in hearing-impaired patients.

The image above is of a neurosphere from Vanderbilt University’s Department of Molecular and Cell Biology.

(Source: amolecularmatter)

A great video explaining evolution, which everyone could benefit from watching, not just creationists!

The simulation is quite fascinating… I would love to see the code! The population genetics behind this, I should also mention, are quite solid. 

(Source: pretendy, via amolecularmatter)

Una gráfica ligeramente preocupante que construí con datos del PREP en tiempo real. La correlación es de .999 - algo increíble dado que estos puntos son menos del 10% de los datos. Una correlación entre 0 - .8 no sería sorprendente, incluso .9, pero .999? La forma en que se hizo el conteo no admite grandes posibilidades de que un correlación de esta fuerza aparezca. 

#Mi nombre es David, soy un estudiante de tercer año de biología computacional en Cornell University (15 mejor universidad del mundo, World Ranking), y de momento estoy trabajando en MIT. No estoy afiliado a ningún partido ni tampoco acuso a nadie - sólo apunto a un evento que estadísticamente es muy improbable dado el método del IFE. 

Una gráfica ligeramente preocupante que construí con datos del PREP en tiempo real. La correlación es de .999 - algo increíble dado que estos puntos son menos del 10% de los datos. Una correlación entre 0 - .8 no sería sorprendente, incluso .9, pero .999? La forma en que se hizo el conteo no admite grandes posibilidades de que un correlación de esta fuerza aparezca. 

#Mi nombre es David, soy un estudiante de tercer año de biología computacional en Cornell University (15 mejor universidad del mundo, World Ranking), y de momento estoy trabajando en MIT. No estoy afiliado a ningún partido ni tampoco acuso a nadie - sólo apunto a un evento que estadísticamente es muy improbable dado el método del IFE. 

fuckyeahmolecularbiology:

“The Black Death” usually invokes mental images of tolling church bells, doctors with beak-shaped masks, necrotic tissue, grave diggers, and the Middle Ages - but that’s far from the whole story.
Meet Yersinia pestis: A Gram-negative, rod-shaped bacterium pictured here (in green) using scanning electron micrography on proventricular spines of a Xenopsylla cheopis flea (in purple). Yersinia pestis, which can infect most small mammals - cats, rats, dogs, and humans among them - is the cause of the bubonic, pneumonic, and septicemic plague. While we may now know that the Black Death was not caused by bad smells, as was once believed, Yersinia pestis has proven extraordinarily persistent - and resistant to eradication.
Because of the zoonotic relationship between Y. pestis, humans, fleas, and rats, the best we can do, to date, is contain outbreaks of the plague when they arise. Most recently, they’ve arisen in China, Peru, and the United States. While the spread of infection is quickly stopped and antibiotic treatment is effective, individual cases of the plague are often not isolated quickly enough, as was the case in China; early symptoms are general and include high fever, coughing, dizziness and vomiting, and resemble those of the flu. Don’t be fooled, though, infection with Y. pestis is still as deadly as ever: The index case in the Chinese outbreak died, and the septicemic plague (thankfully, the rarest form of the disease, caused when the bacterium enters the bloodstream directly), kills within 24 hours.
 Image Credit: NIAID (National Institute of Allergy and Infectious Disease).

fuckyeahmolecularbiology:

“The Black Death” usually invokes mental images of tolling church bells, doctors with beak-shaped masks, necrotic tissue, grave diggers, and the Middle Ages - but that’s far from the whole story.

Meet Yersinia pestis: A Gram-negative, rod-shaped bacterium pictured here (in green) using scanning electron micrography on proventricular spines of a Xenopsylla cheopis flea (in purple). Yersinia pestis, which can infect most small mammals - cats, rats, dogs, and humans among them - is the cause of the bubonic, pneumonic, and septicemic plague. While we may now know that the Black Death was not caused by bad smells, as was once believed, Yersinia pestis has proven extraordinarily persistent - and resistant to eradication.

Because of the zoonotic relationship between Y. pestis, humans, fleas, and rats, the best we can do, to date, is contain outbreaks of the plague when they arise. Most recently, they’ve arisen in China, Peru, and the United States. While the spread of infection is quickly stopped and antibiotic treatment is effective, individual cases of the plague are often not isolated quickly enough, as was the case in China; early symptoms are general and include high fever, coughing, dizziness and vomiting, and resemble those of the flu. Don’t be fooled, though, infection with Y. pestis is still as deadly as ever: The index case in the Chinese outbreak died, and the septicemic plague (thankfully, the rarest form of the disease, caused when the bacterium enters the bloodstream directly), kills within 24 hours.

Image Credit: NIAID (National Institute of Allergy and Infectious Disease).

(Source: amolecularmatter)

Working at the Whitehead Institute at MIT! Amazing!

Hsp90

So much for me keeping a blog. I had final exams, and friends’ graduation. I was busy… But enough excuses.

Today, I present to you Hsp90.

This protein is one of the best conserved proteins - it is present in E. Coli, yeast, C. elegans, and yes, of course, mice and even humans. This protein helps other proteins to fold, and when they misfold, it can help them go right again. 

Hsp stands for Heat Shock Protein. There are many of these, and they are all quite important. Hsp90 is kind of unique though. Whereas other Hsps bind to specific sequences (some bind to nascent polypeptide chains, others bind to short apolar motifs, etc…), nobody has yet determined how Hsp90 chooses its targets, or where it binds. 

Now let’s go a little bit into the structural biology of this protein. It has three domains, the N-terminal domain (NTD), the Middle Domain (MD), and the Carboxy-terminal domain (CTD). The NTD is what binds ATP — the bright spheres in the above image. The CTD is the really dense region at the rightmost end of the protein - its function is to bind to another CTD: If you look really closely, you’ll see the image above has a line of symmetry. This is because the protein I’m showing you is in its dimer form, which means that it is bound to itself. Thus, there are actually two polypeptide chains in the image above that are actually the same. When the chain binds to ATP, it is in the closed conformation. Once the ATP is converted to ADP, the chains actually open, kind of like a scissor, where the handle would be the CTD. Somehow, this motion must help the folding proteins (called clients) to find the correct conformation. How? Nobody knows (but I will be researching this at MIT this summer!!!).

Impromptu

**I know this is a biology blog, but I need to publish this post, as it deals with what I consider to be some of the most important political realities of my country. Feel free to distribute widely. 

            On Friday, May 11th, something highly unusual happened. The presidential candidate had visited the Universidad Iberoamericana in Santa Fe, México City, to speak about his vision for México. He spoke at length, and his answers were met with mixed responses. Near the end, the disgruntlement grew larger, and people asked about Atenco, a name that will go down in history, for it was the bloodbath of my generation, the symbolic (thankfully not the numeric) equivalent of the Matanza de Tlatelolco that has marked our history thus. Now, the ambiguity surrounding the Matanza de Tlatelolco should not surprise you. There have been many accounts of the two massacres that were performed in that once sacred place.

Tlatelolco was the sister city of Tenochtitlan. On the 13 of August 1521, Hernán Cortés defeated the mexicas and took Cuauhtémoc prisoner, defeating the mighty sword of Huitzilopochtli – Jesus Christ triumphed before the heathen gods. The Spaniards estimated that 40,000 mexica warriors were killed in battle. It is in this blood that my country was born, and in this blood we were all baptised, a blood baptism, for truly on that day did water turn to blood, and it was a miracle. In the end, perhaps it is better not to rue the Spanish conquerors too much – war is, after all, war, and the crimes were committed against a foe that the Spanish hated and feared, a foe they knew to be equivalent in might to them. The second matanza happened in 1968, not long before the Olympics in México. Mexican students were protesting, as students often do, when infiltrated agents by the government fired at the military guarding the plaza of Tlatelolco. The military returned fire, not at the snipers who had shot at them but rather at the students. The death count is unknown. While the government insists only twenty youth were killed, witnesses claim that the plaza was filled with blood and bodies. Unfortunately, in the end, we shall never know. The death count is lost or forgotten or hidden. It may be that only twenty youth were killed, but that the city of Tlatelolco, tasting the blood of its sons again, cried, filling the streets with its tears. Any number of deaths can still only be a single death, for two violent deaths are no different than one violent death, for these deaths are not additive, nor multiplicative. The mathematics of death escape us and scare us, and we long for the warmth and comfort of statistics, of strict ratios that can tell us the order of horrors of the many genocides that have plagued our history, but deep down we understand that the infinite pain of one violent death cannot be compared to the similarly infinite pain of twenty deaths. Both cases are a tragedy. Most horrendous of all, however, is the pleasure with which López Ordaz attributed the killings to himself, explaining that he had acted with the legitimate right of the Mexican government to employ force to quell the riots. To my mind, this day stands darker even than that older day of battle, because at least then brother stood with brother fighting a single, united enemy. In 1968, our Mexican elders shot and killed our own youth, driven by the desire for more power.

In Atenco, an old place with an older memory, florists tried to sell their flowers on the street Belisario Domínguez (a distinguished politician who was murdered for speaking out against dictator Victoriano Huerta, and after whom Mexico’s most celebrated medal is named; the irony of the involvement of his name in this incident should not be missed), but their permits were invalid and a police operation was initiated to remove them – forcibly if need be. The operation was not well planned and as a result did not go well; the florists fought back with machetes, and many policemen were injured. As the battle waged on, more than 200 police agents were sent to build a police fence. Over 300 men and women were engaged by the police forces; many of the women were raped, two men were killed, and children, men and women alike suffered physical abuse at the hands of the men of the law. Now, the florists were also not above reproach, as they kidnapped and threatened the lives of several police officers for many hours before the preventive federal police broke up the engagement. However, the appalling forwardness of the state government to use force, and the lack of planning involved in attempting to remove the florists are a serious cause for concern. Oh. I almost forgot. Many of these florists were Native American.

Presidential candidate Enrique Peña Nieto was asked on May 11th at the Universidad Iberoamericana about this last massacre; the massacre that he ordered. He refused to respond at first, but at the end, sensing the disgruntlement of the crowd, he attempted to answer. He claimed that the florists had been a threat, and that he had responded with the legitimate right of the state government to quell the riots. I do not know, but I am sure that a shiver must have gone through the history students present as Nieto’s words brought forth the ghosts of genocides past. With this authoritative response, the candidate of el PRI expected to calm the students down, but he achieved the opposite. It was not lost on the students that the police operation was hastily arranged (perhaps nobody cared to organize it properly?) because the situation presented itself impromptu (not because these were Native Americans! Nor was it because they lack either riches or political power). It was not lost on the students that although dozens of the florists were arrested, only a couple of the policemen were ever charged with anything at all, and none received jail time for their violent actions. Most of all, it was not lost on the students the irony of having the once governor of the State of Mexico say that force is the necessary response of the state to defend human rights in defence of the case that has become the iconic proof that the Mexican government does not actually have any of our human rights in mind. With all of this in mind, the students of a University that has a reputation for being separated from the socioeconomic reality in México began to shout at this man who so gallantly put a halo around his own head. His response, a cynical smile, only made the students angrier.

Peña Nieto left a buzzing auditorium, probably unaware that he had given the last swipe to an angry bee swarm that was now ready to execute the full power of its constitutional and democratic liberties of expression. Outside of the auditorium, hundreds of students rallied against Enrique Peña Nieto. They rallied against him and they chased him throughout the school for at least half an hour, as he struggled to get out, his face slowly showing more and more fear, more and more angst at the fact that he was trapped, that he could not get out. I can only imagine, as the students shouted “MURDERER!” at him, or as they shouted “WE SHALL NOT FORGET ATENCO”, that he must have felt the same way those florists felt when they saw the Mexican Federal Preventive Police rushing towards them, realizing that they were facing a foe with superior weaponry, training and, most important of all, far superior numbers. The students rushed towards Peña Nieto, blocking his path, forcing him and his enormous guard to turn around and look for a second exit only to find themselves blocked with more students. Their numbers were overwhelming. The situation almost, almost out of control. Yet, for all its dialectic violence, the insurrection at the Universidad Iberoamericana was not out of control; it was not actually anything other than an exemplary demonstration of the power of non-violence. For all of the students’ contempt for Peña Nieto, only one unfortunate shoe was thrown at the presidential candidate, narrowly missing him. The students could easily have allowed the situation to turn violent, but their democratic and tolerant self-restraint was more powerful, more symbolic, more progressive and most of all, more Mexican than the cynical corruption of our bureaucrats. This 11th May of 2012 brought the dead of the massacres to life again – the students who died in ’68, and the heathen god of Quetzalcoatl and Tlaloc lived once more to see the day in which the Mexican youth stood up to their corrupt elders in an act of supreme tolerance and resistance.

Perhaps it doesn’t matter who wins the 2012 elections. We all know they are rigged. We all know that 1 vote for AMLO, or 1 vote for Josefina Vázquez Mota, is in fact 2 votes for Peña Nieto. We all expect a blatant fraud in which the PRI will take its place once more at the head of the snake that is in the shield of our flag. But this time, it may be different. Our students, our youth have shown with the demonstrations that they are leading today all over the country that they are ready to exercise their democratic rights to the fullest. Our students have shown that they are willing to stand up to the power of money, government or even guns to make the future better not for themselves, but for their friends and family, for their community and for their country. The blood of the students who died in 1968 was not shed in vain. Their blood baptized our generation, infusing it with the realization that if we are not willing to stand up to power, we will never achieve our goals.

Mexico has never recognized us, its youth. We are the holders and, simultaneously, the receivers of the largest potential wealth of our country. However, we are denied the tools to make use of that potential. Our national school system is in ruins. Our universities do not receive enough funds. There are no scholarships for hard-working youth, and there are no jobs for us, regardless of whether we obtain a bachelor’s degree or not. There are few exchange programs with other programs, and no support for youth immersing themselves in science. We are referred to constantly as problematic, illiterate, caring only for television and videogames. And yet, what Mexico has never said, what Mexico has always failed to admit is the fact that it is our elders who have failed us! When the Spaniards came to Mexico, they instituted a complex caste system in which even the sons of Spaniards born in Mexico could not have access to certain job posts. Mestizos could not reach more than a certain level of education. Unwittingly (or perhaps quite wittingly), Mexico has chosen to continue this approach, by systematically denying its youth the fruits of a better future. Our history has shown us that a system like this can only be resolved through its upheaval. Today, college youth are beginning to do just that. Through the peaceful, united demonstrations that are on-going today, the Mexican youth has begun its path to true democratic freedom. This youth will show that democracy does not just mean freedom to choose; it means freedom to choose in an informed and educated manner. Such a system is a system that has never before existed in our republic. It is a system that el PRI both fears and respects, for it is the only system that can completely wash away the curse of the past. I hope that regardless of the results of the 2012 election, our youth will continue to inform the rest of the population and will continue to dog our politicians, demanding analytical and thoughtful answers to our questions. Maybe we will not have democracy in 2012, but so long as our universities and college systems remain robust production houses for informed youth, Mexico can have hopes of becoming a free country at last. 

fuckyeahmolecularbiology:

Fluorescence microscopy image of Anopheles gambiae (mosquito) heart, magnified to 100x.
Image Source: Nikon Small World Photomicrography Competition.

fuckyeahmolecularbiology:

Fluorescence microscopy image of Anopheles gambiae (mosquito) heart, magnified to 100x.

Image Source: Nikon Small World Photomicrography Competition.

(Source: amolecularmatter)