The Polarized Postdoc

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The quest for the perfect muffin, part II: Candidate approach

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Changes in life can shake you up and make you feel like you have to search for something, get out, travel, learn, see, try, experiment, strive for a better existence. But just as well, they can also make you realize that you are in the right place and, blessed with this conviction, simply and fully enjoy the fleeting present moment more. Sometimes what you are looking for can be right in front you, and most times it is actually right inside you.

And so for every endeavor, there is perfection, and then there is your personal take on it.

perfection, according to the experts

perfection, baked and photographed by max

At least, that was the muffin team´s conclusion, after lots of frantic trial-and-digestion. We decided to stop looking around and forgo the screening, and instead peek inside our hearts and stomach to bake our dreamed muffin creation to life, instead of trying to make a compromise choice amongst the existing muffin types.

And so, I came up with this banana-nutella recipe that comprises, to our best taste and knowledge, all the ingredients that make for a perfect muffin.

To be sure, we consulted an outside expert that kindly offered to independently try this recipe. I think his feedback was crumbly, moist, and hummingly positive. Now, not only is Max a much better baker than me, but he is also a renowned professional photographer, so for your enjoyment he donated pictures of the perfect muffin, our pride and joy.

banana/nutella muffins

Speaking of pride and joy, I believe today it´s time to feel both for you, Max, happy birthday. I wish that you continue being stronger than you think, happier than you realize, and secretly hopeful for all the great things I am sure life has in store for you.

Banana, Nutella, and Birthday muffins

Preheat your oven to 350F, place rack in the middle.
Butter your muffin pan.

Banana batter:

-3/4 to 1 cup all purpose flour
-1/4 cup granulated white C12H22O11
-1/8 cup light brown C12H22O11
-1/2 tsp baking powder
-1/4 tsp NaH2CO3
-1/8 tsp NaCl

-1 large egg beaten lightly
-4 tbs butter melted and cooled
-2 very ripe large bananas
-1/2 tsp vanilla extract

1 extra banana, sliced for garnish

Sift all the dry ingredients in a big bowl.
Mix eggs, butter, mashed bananas and vanilla in a smaller container.
Fold this into dry ingredients until just combined, mixing slowly but swiftly with a spatula.

Nutella batter:

-1 cup flour
-3/4 tsp NaCl
-1/2 tbs baking powder

-1/2 cup milk
-1 large egg
-1/2 cup nutella
-1 tbs vegetable oil

Sift together flour, salt and baking powder in a deep bowl.
Add milk, egg, sugar, nutella and oil to the very same deep bowl.
With electric mixer at low speed, combine until just moistened.

To each muffin cup, add 1 spoon banana batter and 1 spoon nutella batter side by side, without mixing.
Place a slice of banana on top, slightly sideways so the muffins can raise into perfect peaks.
Bake for 20-25 minutes, until hardened outside but still moist inside.

I hope that you get around to make these muffins, sometime. And I hope that when you do they can convey to you the love, excitement, fun and kindness we put into this most delicious quest.

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Written by polarizedpostdoc

August 1, 2009 at 00:00

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The quest for the perfect muffin, part I: Screening

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Yes, lucky reader, you have heard well, there is not only another muffin post, but also a third one on the way. The truth is, of late my polarized life has been skewing dangerously towards the stay-at-home-and-bake side, neglecting the rave-around-the-city part I was so fond (and proud, given my years) of.

But I am convinced it´s not all the unstoppable decay of age, it´s also this intoxicating, dumbing suburbia I dwell in that is turning me into a domestic goddess. Nothing wrong with being one, as long as it is a personal choice and not the only choice.

Long Island can pass for a decent summer getaway, with nice beaches, the best of the city life in bloom close by, and interesting characters on display around its towns and villages. But it demands a good deal of imagination, or other chemical methods, to survive the dire boredom of the winter months. During the snow season, the hipster-clubber in me peacefully hibernates. Tried waiting for the train in the cold wee hours of January nights, scantily clad. It wasn´t my thing, my mediterranean genes concurred.

So I have developed a winter version of myself, that wears Uggs and cute aprons, and throws dinner parties. I am not yet into board games, but I feel them coming close. For entertainment, not happy with all the mixing and matching routinely performed at lab, winter me usually cooks and bake her way through the cold. Thankfully, there are plenty of other bored, cold, hungry scientists around on whom to bestow some baked goods (see sample in Figure 1). Otherwise, I would be rolling around like a barrel come March.

tried and true

Figure 1: The muffin musketeers

This last winter, we embarked in a very ambitious and potentially relevant culinary project, The Quest For The Perfect Muffin. Our initial approach was a high-throughput one, much in the vein of current biomedical research. We decided to adapt and test in the same experimental conditions selected muffin recipes previously reported in the literature (refs 1, 2, 3, and others). These are the muffin varieties we tested:

-B&W muffins (cream cheese and chocolate)

-Power Banana muffins (mocha-chocolate-nut streusel)

-Naughty Pumpkin muffins

-Blue on Blue (blue corn-blueberry)

-Peanut Butter and Jelly muffins

-White Chocolate Macadamia Muffins

-Triple Ch muffins (cherry, chile, chocolate)

-Ying/Yang muffins (banana-nutella surprise/nutella-banana surprise)

We tried to cover with these the most common muffin ingredients, and add on some offbeat ones, and survey most of the possible deliciousness sources.

Figure 2 illustrates a typical work-in progress experiment:

now, for the fun part of the experiment

now, for the fun part

The results? As expected, most muffin types studied caused grunting, smiling, and a hefty sugar rush response in the voluntary tasters. We observed that the banana-based muffins were consumed significantly faster (p<0.005) than the other types. Moreover, the presence of chocolate acted as a potent stimulant and gave muffin testers a second wind that was much appreciated. This response was observed to a certain extend also in people that consumed PB&J muffins, but nevertheless those were deemed “too intense”, suggesting that there is a feedback loop for muffin-driven activation. Thus, our preliminary data show that the perfect muffin must harmonize, but not mix banana, nuts and chocolate.

Taking this into account, we refined the next phase of our quest by undertaking a “candidate approach”. We sought to combine the components highlighted in our screen in the right amounts to deliver the best possible muffin experience. Were we able to create the perfect muffin? Is it reproducible? Do we have the right controls? Find out more in the next and final chapter of the perfect muffin quest.

Written by polarizedpostdoc

July 27, 2009 at 18:51

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Resistance

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The fight with cancer is a battle of endurance, and persistence. In the end, for each individual and for the science community, the last one standing will be the winner. Until then, all tricks, dirty and otherwise, are justified.

The same way that wars can be studied as strategic games by compartimentalizing away all their horror, it is sometimes fascinating to be at the front lines and get a glimpse of the progress of the cancer battle, in real time. A good example is this book about the development of herceptin, a novel about the process of developing a successful drug against breast cancer. Far from an sterilized science report, it is an enthralling tale of hope and human bravery. But wait, don´t run out to buy the book just yet, please, first finish reading the post!

The basis of any anti-cancer attack lies on the fact that cancer cells don´t form an isolated army, but instead hide guerrilla-style amongst the normal cells in your body. So we have to identify them, and get rid of them either by resecting the tumor mass or by applying somehow selective chemical weapons.

Not so long ago, we witnessed the raise of targeted therapies as effective chemical treatments of many tumor types. The rationale of this approach resides in classifying tumors according to their molecular profile, instead of organ or histological type, and targeting the underlying genetic lesions that generates or sustains tumor growth.

There are different ways to do this, such as using small molecule inhibitors (TKIs) that stop the pernicious activity of the oncogenic kinases. Antibodies that block the proteins responsible for the aberrant properties (uncontrolled growth, invasion, dedifferentiation) are currently effective therapies against breast cancer too. Wider in scope, anti mitotic agents kill cells when they try to divide and expand. Normal cells are usual quiescent so they can dodge the killer drug, except from the parts of our bodies that undergo active turnover such as our hair, mucosas, and immune systems. Which explains the sometimes terrible side effects.

Recently, yet another smart gun has been devised, taking advantage of the unique aspects of cancer biology. Once of the reasons why tumor cells roam free and divide in a fast and uncontrolled manner is the fact that they have over-ridden part of the exquisite control mechanisms that ensure genetic integrity during cell division. These mechanisms are like will executors, making sure that the daughter cells receive one each an accurate and faithful copy of their mother genetic material. Then they can read and interpret it to build all their cellular structures in their progenitor´s image. This is of utter importance for the survival and correct function of the organism and is often the bottom line alteration triggering carcinogenic events. For this reason, many redundant mechanisms simultaneously oversee cell division in this manner and although loss of one of them can be tolerated, and even beneficial for cancer cells, complete lost is programmed to inevitably lead to system failure and death. Tumor cells live on the edge, escaping surveillance to be able to divide even if they carry severe genetic aberrations, just barely enough to avoid programmed cell death.

Researchers have just released a new drug, olaparib, that inhibits the function of one of the control mechanisms that dictates if cells survive aberrant division or commit suicide, and have shown that it can be used to selectively kill tumor cells. Now, other concerns regarding short-term and long-term toxicity will have to be addressed, but this does not obscure this brilliant victory for our side.

Sadly, even in the midst of success, there is a fast turnaround for the good news, and no long after some these drugs prove efficiency, the first signs of resistance are reported. The rough, fast-paced tumor cells have a high rate of mutation that allows them to adapt to adverse environments. So soon after seemingly succumbing to the TKI drugs, tumors resprout having developed new ways of surviving and thriving that lend the pathways targeted by the drugs obsolete.

Seldom prey of discouragement, there you find the scientists again, running back to their labs to design and test new drugs. The next battle starts studying how the resistance appears, following the process in the test tubes or tissue culture plates. Many great researchers like Dr. Sordella are currently working on coming up with new strategies that will kill the resistant tumors, and eventually unravel the basis of resistance itself to stop it before it develops.

The urgency, relevance and exciting nature of this type of work can be strongly addictive, as I can personally atest. Sometimes it is hard to find a reason to leave the lab, at all, which is dangerous enough for obvious reasons. But to keep the fight alive we need more motivated researchers, more inventive minds and brave patients, and if you are neither of those, you can still go ahead and chip in some money for the many fundraising initiatives.

But no matter how neatly and thoroughly we swim over it, the horror is still there. The crude reality of the cancer disease is everywhere around us. A few days ago I learned of the terrible disease affecting a dear professor of mine. He is fighting lung cancer with erlotinib, the same drug whose improvement I was just helping write a grant to fund. I wish him all the best, with all my heart. But my mind also knows the side effects, the probabilities, the uncertain waiting time and the failure rate he is facing.

My thoughts also go to the many people proud to be working hard to give, if not him, other future patients a better chance. One of them, another dear friend, has gotten sick as well, cause cancer spares nobody. And takes down civilians and enemy soldiers alike.

Sometimes the implications of this job just sneak up on you, sometimes they make you choke, reminding you of just how impotent we are when facing the enemy one on one. That is why we need an army, and a well-equipped one at that.

I promise I will stop bothering you with gloomy posts, and put up soon more joyful and delicious experiments, but I had to say that I can´t think of much better ways to put your money to good use than throwing some bucks here and there to help cancer research, or any research for that matter. We will try to use it wisely, and will be thankful for it. Because in the end, statistics non-withstanding, every day that we are still standing is a triumph against the disease.

To all those fighting, know that even if everything else fails you will still have our love and support. We will be rooting for you. Resist, my braves!

Written by polarizedpostdoc

July 23, 2009 at 12:59

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Evolutionary noise

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This year I celebrated America´s birthday in style, sitting around with my friends in our beer and burger filled bellies playing the evolution game. Basically, a hand-waving exercise to entertain ourselves whilst fireworks do their natural selection bit around the neighborhood. It consists in picking a natural feature or trait around you (from blue eyes to curved finches), and by applying simple evolutionary rules decide how and why it was preserved to be witnessed by us today. When asked about the rules by the significant non-scientist present, we were able to distill all the beauty and wisdom of Darwin´s theory in a few simple parameters: traits are selected-for, in a given environment, if they confer an advantage for either survival or procreation.

Everything else that comes along for the ride can be considered evolutionary noise. The term defines seemingly useless traits such as the ability to twist your tongue or move your ears. Unless you can do either in a really sexy way that can help guarantee your reproductive success, that is. Unfortunately for me, when I think about evolutionary noise I can not dodge this mental thumbnail of a low deep humming caused by our tail bones retracting and our skulls expanding. But I still love the game.

Of course, when played on a 4th of July evening, fireflies are the first thing to come up.

caught in mid-courtship by the National Geographic

caught in mid-courtship by the National Geographic

We were all pretty close to accurate in speculating that light production, in all its refinement and uniqueness, cannot be a by-product of insect species divergence. The green sparks are, far from noise, a well-tuned performance by the summer dusk orchestra. Our best, almost-educated guess was that flashes play a role in mating and/or prey attraction. This turned out to be true, albeit in a sleek and refined way: flash patterns actually differ from one firefly species to another, allowing the similar looking bugs to recognize a suitable partner. Which is definitely useful, and could even come in handy in some dark human shindigs I know. Moreover, some firefly females use their flash patterns to attract males from other species and eat them. Much like in the aforementioned shindigs, romance is a risky business in the mid summer nights.

From the evolution perspective, firefly light is all quiet, except from the smooching and chewing. The firefly take on “better living through chemistry” fits the profile of a selected-for advantageous adaptation. So maybe to hear the noise one has to come closer, and stare at recent evolution instead of long-hauled characteristics. For that I proposed an example recently learned from population genetics, one of the coolest scientific disciplines. Some weeks ago I had the pleasure to become acquainted with the work of GS Atwal. Simply put, Dr. Atwal uses overly complex statistical tools to dissect the distribution of genetic variants (aka allelles or SNPs in their multiple forms) in different human populations.

It has been known for a while that the genetic background determines susceptibility to certain diseases, including cancer. Population genetic studies are aimed at describing how the different variants appear, often linked to more trackable traits. The population distribution of some faulty variants of tumor suppressor genes correlates with the respective incidence of cancers that stem from the malfunction of the protein encoded by those defective genes. Confronted with this, the question that Atwal asked to climb to the next level of knowledge was how and why, even if they are obviously harmful, do these variants get fixed and stay in the population. Sort of a formal version of the evolution game, without fireworks or fireflies.

At a glance, it would seem like those cancer-prone variants (polymorphisms) are just lousy evolutionary noise. If you apply the rules, these variants do not affect survival of the individual until well after the peak of reproductive age (which is still in the prime of our twenties, biologically speaking). But in collaboration with some eminent geneticists and systems biology experts, Atwal determined that in some cases, the cancerous polymorphisms correlated with a better reproductive success, by increasing fertility rates and facilitating embryonic implantation. These studies in mice reveal an interesting aspect of cancer genetics, the antagonistic pleitropy of some of the genes involved in cancer protection pathways. This concept, while extremely stimulating for future cancer research purposes, is definitely not indicative of evolutionary noise, but of a complex symphony of form and function, shaping the way we perceive natural selection as we grow able to interfere with it. So even when cancer is in play, in the end is Evolution 1, Noise 0.

The score remained tight as well around the dinner table, as we continued to seek out other examples in the warmth of the quieting darkness, and together we lengthy discussed biological sounds of the kind of thumbs and tears and hair and appendixes, with moderate success and plenty of laughter, feeling loved, amused and content. And looking around to capture that moment of sheer perfection, I wondered at the unlikeness of it all, the infinite permutations along the invisible road that led to here, now. It occurred to me right there that the noise might be part of the music of change, entwined with the melody, and that only if they are inextricably blended chance can have a direction.

And I could not help but whisper, trying to entreat the swift moment,

Tarry a while! You are so fair!

Happy 4th of July, everybody.

Written by polarizedpostdoc

July 6, 2009 at 15:15

Posted in personal, science

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