The quest for the perfect muffin, part II: Candidate approach
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, 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.
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.
The quest for the perfect muffin, part I: Screening
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.
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
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.
Karma muffins
Hypothetically speaking, if one were to accidentally back into someone´s car´s door, and drive away in a hurry without leaving a note, and then some weeks later someone else would in turn back into your car´s door and scram (leisurely or hurriedly) without leaving a note, it must mean that the universe, using the active forces of karma, has just spun around enough to recover its equilibrium.
But rationally speaking, that universal balance cannot, possibly, be ever preserved still. The logic of supernatural forces implies that when you backed into someone´s car the first time, the owner probably deserved it somehow, and you were just a toy being brandished by karma´s hands. So the bad energy merely got transfered, or derived from good one. And so on, and so forth, ad infinitum, it follows that an endless chain of unfairness fuels the dynamic balance of the universe.
Whenever I start thinking like that my heart gets dizzy. I have to admit that I am not much of a believer. It´s not personal, you gods and goddesses and earth energies, it´s just that I have trouble with the idea of believing itself. Of choosing to accept instead of to proof, or discover. In absolute terms, though, a life of faith sounds much more relaxing than endlessly trying to answer all the “whys” and “hows” and wtfs” around you.
battering heights
This weekend, as a mental vacation from worry, and to make up for some recent bad energy transfers, I decided to give karma a try, scientifically speaking. I always picture karma like a molding water mill wheel, Ignatius Reilly-style. So my premise is that if karma is some sort energy cycle, not created or destroyed but just transformed by human actions and consequences, it must be amenable to measurement. It has to have a quantifiable unit, kJs perhaps (karma-joules, not kilo joules, thank you).
And if we have our units, we can devise a system to calculate how many KJs are there in a hug, a kind salute, a ride to the airport. But as we don´t know either the exact parameters of the energy conversion reaction (is it exotermic? explosive? catalyzed?), save for that sometimes it includes a kinetic intermediary in the form of car crashes, we need to create good energy, from scratch. More accurately, from our very own chemical potential. AKA, the wheel of life.
top o´ the muffin
To do so, and establish a proper standard that we can apply to daily life, I figured I could make a well-known vehicle of good energy, that comes already aliquoted in individual doses. So instead of worrying, I adapted a warm looking muffin recipe to my non-dairy, berry-crazy standards. Then proceeded to bake them and spread them amongst my friends and folks, who received different doses of the sugary vibes. Now, I plan to just sit back, hang out and observe how the good karma expands and extends from my oven, into the hostile world, perhaps in waves of good luck or strikes of love. If we apply some simple exponential amplification rules, it is likely that this experiment might keep me busy for a while. So for now, worrying will have to wait for the next wheel´s turn.
(Good) Karma Muffins
Procure:
-1/2 cup margarine
-1+1/4 cup granulated sugar
-1/2 tsp salt
-1+1/2 cup all-purpose flour
-1/2 cup cake flour (optional, you can use AP)
-2 large eggs
-2 heaping tsp baking powder
-1/2 cup soy milk
-1 tsp vanilla extract
-6 ounces each of raspberries, blackberries, and blueberries, fresh or unthawed, sprinkled with:
-1 tsp sugar
-1 tsp cinnamon
-1 oven at 385F
-1 hand mixer
Perform:
-Sift flour and baking powder together and set aside.
-Cream margarine, sugar and salt with until soft (one day we must discuss the scientific value of baking terms such as this, or “until just combined”, “fluffy” or “just moist”)
-Add eggs and beat until fluffy, to your best judgement.
-Pat berries dry on a paper owel.
-Into the liquid mixture, fold alternatively one thir of flour, one third of milk, repeat until just combined. Add vanilla.
-Sprinkle berries with sugar and cinnamon, fold into batter.
-Pour 1+1/2 tbs of batter into greased muffin cups. I always have trouble calculating how much to aliquot, and can never seem to avoid putting too much. This measure seems to produce some handsome, pointy doses of good energy to share.
-Incubate in the oven for 20 minutes, or until golden and dry according to the international toothpick standard.
-Cool for 10 minutes on a rack, invite friends over, have them with hot chocolate, and rate your muffinity according to the width of the smiles and volume of grunts elicited. Good luck, and good karma.
Resistance
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!
Monkey Business
While some of us are scooping summer bliss out of ice cream cones, the on-shift scientists continue their quest for the secrets of life. In this case, of eternal life. But of course, their proposed recipe for extended youth has major catch.
Life-prolonging phenomena are harder to come by that life-ending ones, but nevertheless some thirty years back it was discovered that caloric restriction diets effectively prolonged life span. For those of us who make our pies with lard, there was the consolation that those results came from studies in mice. Arguably of limited relevance for human biology, mice, with their intense three years average lives, were still he model organism of choice until know. They are a useful albeit imperfect system to study longevity, given the obvious drawbacks of setting up experiments likely to last longer than the researcher´s life span.
But eventually, curiosity and rigor prevailed and a group from Wisconsin stared thirty years ago to test whether caloric restriction had an effect on longevity. To this aim they used the closest non-human primate, the rhesus monkey. 30 males and 30 females were placed on either on a control or a low- calorie diet for 30 years. For those of you interested in those things, the low diet contained 15% protein and 10% fat.
During the course of the study, the investigators examined aging-related parameters, namely mortality and onset of related conditions such as cardiovascular disease, brain atrophy, cancer and diabetes. The results, contrary to non-conclusive previous studies, unequivocally show that a lower calorie intake expands life for an average of ten years. Moreover, leaner monkeys seem to display a healthier condition overall, with delayed onset of the diseases studies.
When compared to their take-out dinner mates (left) they look like this:
drop those cupcakes!
These pictures are striking, and gave raise to a very healthy, amusing debate amongst my fellow scientists. Of note, though, these data compare “normal” to “low” calories, and we can not extrapolate on the negative effects of a high calorie diet on the life span, a subject still under heavy debate.
Looking at this compelling evidence, we can reflect on quantity vs. quality. There are no standarized measurements for a good life, but I still spent a long time staring into the monkeys´ eyes. Trying to decipher if, beyond all those physiological readouts, there were other differences. Other than physical appearance, the paper does not comment on the quality of the macaques lives. Are the low-calorie diet monkeys more active, more creative, do they socialize more? Are they smarter, funnier, can they dance and sing better?
I don´t care, just give me a burger
While those questions are irrelevant in the context of the presented research, they might be of interest for you as they are for me. In fact, the end point count of travels and stories, parties and midnight swims and hikes and dinners with friends and cakes in the oven may be more important to you than scoring those extra years.
To date, science can´t help you evaluate that, and the question is only yours to ask. Is a life of lyophilized broccoli worth getting 30% more years? Or living at all? If the answer is yes, now you have that option, just have to keep following science´s advice. If the answer is no, on the other hand, you might want to navigate in a different direction.
Whatever your choice may be, happiness is still not a monkey business. So however long and flavorful you decide to make your life, hope you make the most of it!
Empanada
“Empanada” is a Spanish word with poignant connotations for my life right now. Literally, it means “breaded” or “tucked inside bread” and usually refers to a traditional dish from the north-west of Spain. This region delimited by mountain ranges and crooked coast lines is the home of velvety, furry grassed hills and the rich silver stretch of the Atlantic ocean that we call Cantabric sea.
In slang, to be “empanada” refers to that distracted state in between spirited away and absent-minded that can be experienced when you have many loose ends slashing out all over your brain. Which is exactly how I feel these days. Tucked between the dough of fate, in a cloudy haze, at times dizzy or giddy with fear or excitement. A true case of empanada.
Aside from the human version, there is also the bite size one, empanadillas, that are pretty much the local take on dumplings. They look like puffy dough balls, and are filled with an assortment of the seasonal earth and sea goodies at hand. Much like this:
Reagents
veggies ready to take it to the next step
feeling the filling
one, two, three... empanada
Evolutionary noise
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
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.
Know your enemy
Contrary to what the buzz says, new developments in the war against cancer are not that hard to come by, or that minor. Those important characteristics in anti-cancer advances (speed, abundance and relevance) are in direct correlation to the money and effort invested in research. Which is why we need to keep committing both to an unfaltering fight. Because even the smallest victory saves countless lives, present and future.
It is my personal experience that usually cancer research elicits respect, and often encouragement, from lay audiences understanding the fierceness of the fight on both sides. But for some reason, lately cancer research is under a heavy flak of criticism based on lack of progress and innovativeness.
I disagree with both claims as strongly and biasedly as I possibly can. And I could use my insider´s view to go on a really righteous and uptight diatribe about why and how, exactly, but in my best scientist behavior I am going to just let the facts speak for themselves.
Just recently, two new therapies have been announced, one of them stemming from a pretty revolutionary and novel approach called synthetic lethality. In an agile leap from ideas to cures, this new concept has already provided effective therapies for one of the most aggressive and poorly understood forms of breast cancer, the so-called triple negative tumors. This positive response represents not only a victory, but a spearhead propelling us ahead in the game, opening new possibilities for treating other forms of the disease.
Because contrary to the rules of engagement proposed initially when we declared this war against cancer, the enemy is neither one, nor static. Cancer is an ample term that fits in solid armies of tumors growing silent and morphing in many different organs, guerrillas of circulating tumor cells ready to invade new territories, dormant mutations that act like secret agents turning normal cells to the dark side, collaborationist immune system components, and many more wicked weapons yet to be uncovered.
It has been clear for a while that the most effective way of winning is by getting to know your enemies, in every terrific form they take, and fight them to the ground one by one. This logic is simple and powerful enough, on top of tried and true, and I am perplexed as to why mass media can´t seem to accept it. There is not going to be a single bullet solution for cancer, but we are sure going to keep winning battles, if only they let us fight in peace.
One of the most poignant ones is the ongoing quest to discover how tumor cells can leave their niche and, evading several layers of surveillance, infiltrate other organs spreading the disease and making it impossible to control by surgical methods. Last week I had the privilege to witness an outstanding scientist describing how his group has devised a novel system to observe in real time the sly tricks of invasive tumor cells, shedding some light about the initial steps of this deadly process called metastasis.
The group of John Condeelis managed to put a microscope video camera inside a mouse breast tumor, and monitored the movements of tumor cells. In their recordings, we are able to witness in awe the showdown between immune cells (the vigilant macrophages) and tumor cells, as they chase each other´s chemical scent while sliding down the tumor´s scaffold of collagen fibers. The tumor cells swiftly follow the macrophage signal, EGF, to the blood vessels, where they can extend cellular protrusions to break into the blood stream. Hence, the first step towards invasion has happened, silently and far from the tightly surveilled edges of the tumor.
green tumor cells ambush a red blood vessel, ready to go on a invasion mission
Fireflies
We don´t have fireflies back home. But there are plenty here in the golden coast of LI, so many that people whisks them away like regular airflies. Me, I can´t get over them. And I am so grateful for it, cause it means that I have spent enough time of my life without them to ensure that from now on they will stay fresh and new forever, always. It is like getting a bit of your childhood back every time, a rebate.
The golden coast of LI makes me feel that way about science too, sometimes. If you are a local scientist, when the conference season comes by in the summer you are constantly stumbling upon outstanding talks that light up the dark auditoriums. Instead of just fizzing around your sleepy head, they warm up your heart making you feel the excitement of that first biology class, fresh and new again. And much like real fireflies, I don´t remember ever experiencing anything like that back home. So for a healthy daily dose of amazement, you usually just have to look the right way, and persistently keep your eyes open for wonders.
It seems like after some lackluster beginnings, last week we finally kick-started the summer, and I saw my first fireflies, both real and imagined. To fully appreciate the first ones, I am afraid you would have to move here one August, muddle through the hot wet air with a cold beer in a sweaty glass, and sit quietly near some bushes at sundown.
But for the second ones, you don´t need to leave your seat, just keep your eyes open and continue reading these posts. I am going to try and transmit the feeling of being mesmerized by summer science, time and time again. Cause as my friend Max just put it, there are a billion outlets for hard data, but there is only one outlet for me, and you are in it.
The shape of cells to come
By now you are aware of the importance of polarity for the correct function of essential biological processes. And you are asking yourself, but where does it start? How does it work? What are the cues that help cells identify the external asymmetry, and translate it into an internal one? Well, those questions are still being actively pursued by many talented scientists, and also regular ones like me. And as in every good story, our quest started out by sheer chance, or its technical counterpart, serendipity.
But in order to grasp polarized organization in all its beauty, we first need to get acquainted with regular organization. The mechanisms and pathways that determine unpolarized cell shape comprise a common core that is going to carry out the polarity differentiation program. So let´s unveil them, briefly I promise.
Like the structure of a building, or even the bones in your body, cells are equipped with a microscopic skeleton, the cytoskeleton. It is a system of interconnected filaments and tubes that provides the physical support and scaffold for all the cellular organelles. The interior of a cell is little more than a container for different subcellular structures, that in turn subdivide ad infinitum into smaller structures. To orient you inside this fractal microcosmos, this is a depiction of how we scientists see the inside of a cell when we close our eyes (color choices may vary):
animal cell, from A Blog Around The Clock
The cytoskeleton components not only keep everything in place, and give structural support to what is fundamentally a bag of liquid, but they also act like rails, or highways, through which cellular components can be shipped from one location to another. This shipping process usually goes from the cellular factories that assemble proteins and lipid structures, through the packing stations, round the energy central, to their target locations. For example, our cell may synthesize an adhesion protein to attach to its neighbor cell, and ship it to get polished and refined (usually by adding sugar and lipid tails and coats). Then the adhesion molecule will be directed through the cytoskeletal meshwork to its place at the plasma membrane, where it will insert itself and stretch out to grab on to an identical molecule from the adjoining cell. And just like that, life can go on.
Cytoskeleton networks and the sorting machinery, together with the membranous system of compartments, constitute the stable structural basis that enables the cell to function as such. But they represent a plastic arrangement that lends itself to multiple modifications and slight variations. It is thus exciting to think a step further about how this organization can be adapted to support not just a cell, but an asymmetric one. As usual, the answer to this is simpler, smarter, and far more beautiful than we could have imagined.
