Algae Disco
All posts by Leah Burrows
Chill out! You control your stress response
Think finals are stressful? Try being chased by a lion.
Humans evolved in a dangerous, threatening world where stress usually preceded bodily injury. As a result, the evolutionary theory goes, our stress response system jump-starts our immune system, triggering the deployment of white blood cells and increased expression of the inflammatory gene interleukin-6 (IL-6) into the blood stream.
As part of our immune system, IL-6 can help stave off infection and promote wound healing, but if left unregulated, this inflammatory agent can contribute to cardiovascular disease, cancer and Alzheimer’s. Knowing where and how in the body various forms of IL-6 are produced is an important step in understanding how stress relates to disease.
In a recent study published in Brain, Behavior and Immunity, Brandeis researchers discovered that one’s perception of stress directly impacts how genes express stress. The paper was written by graduate student Christine McInnis and professor Nicolas Rohleder, and co-authored by Danielle Gianferante, Luke Hanlin, Xuejie Chen and Myriam Thoma.
Researchers have long known that IL-6 proteins increase in blood plasma after stress but this is the first time scientists have observed increased activation of the IL-6 gene in white blood cells as a stress response.
The size and duration of the increase is closely tied to perception and mood, according to the study. The more a person stresses out, the more IL-6 is expressed.
“Stress perception initiates the gene expression and self-reported mood changes are directly related to the size of the gene expression response,” says McInnis.
In other words, we can, to some extent, control our genetic response to stress by moderating how we perceive stress.
“If you learn to control your stress levels, your genes will follow,” says McInnis.
So next time you’re stressed about a big test, calm down: It might be a bear of a test, but it’s no lion.
This research was supported by the American Federation of Aging Research.
Science friction: Unlocking this basic force may lead to futuristic technologies
Here’s the rub with friction — scientists don’t really know how it works. Sure, humans have been harnessing the power of friction since rubbing two sticks together to build the first fire, but the physics of friction remains largely in the dark.
In a new paper in Nature Materials, Brandeis University professor Zvonimir Dogic and his lab explored friction at the microscopic level. They discovered that the frictional force is much stronger than previously thought. The discovery is an important step toward understanding the physics of the cellular and molecular world and designing the next generation of microscopic and nanotechnologies.
The research was conducted as part of the Brandeis University Materials Research Science and Engineering Center.
Dogic and his team focused on the frictional forces of actin filaments, essential cellular building blocks responsible for many biological functions including muscle contraction, cell movement and cell division. All of these processes require filaments to move and slide against one another, generating friction.
Scientists assumed that the frictional forces of these movements were minimal, acting more like weaker hydrodynamic friction — like pulling an object through water — than the larger solid friction — pushing an object across a desk.
But Dogic and his team observed the opposite. They developed a new technique to measure friction, and when they dragged two actin filaments against each other, they observed frictional forces nearly 1,000 times greater than expected — closer to solid friction than hydrodynamic friction.
This is due, in part, to interfilament interaction. Imagine filaments as two beaded strings, one on top of the other, pulled in opposite directions. As the strings move, the beads must go up and over their counterparts on the opposite string, generating even more friction. By observing this interfilament interaction, Dogic and his team were able to measure the frictional forces and tune them, altering the forces to include more or less friction.
“Before this research, we didn’t have a good way of controlling or understanding friction,” Dogic says. “We still have a lot more to understand but now, one of our oldest sciences is becoming less opaque.”
The paper was coauthored by Brandeis scientists Andrew Ward, Fiodar Hilitski, Walter Schwenger and David Welch; A. W. C. Lau of Florida Atlantic University; Vincenzo Vitelli of the University of Leiden, and L. Mahadevan of Harvard University.
This research was funded by the National Science Foundation.
#TheDress Effect: What you see isn’t necessarily what’s there
Last week, a poorly lit picture of a dress sparked one of the fiercest — and perhaps most meaningless — debates in Internet history: Was it white and gold or blue and black? Now that the dust has settled, and the definitive answer established it’s blue and black, it’s time to move onto a more important question: Why did people see the dress differently? ReAction asked biology professor Stephen Van Hooser to break down the science of the dress.
We tend to think we are able to understand the world perfectly through our eyes. In reality, our visual system makes best guesses with limited information. Take, for example, the fact that the world is three-dimensional but the images on our retina are two-dimensional. Our visual system has to make guesses as to the locations of objects based on this two-dimensional image.
Visual illusions force us to confront the fact that the brain still makes guesses, or especially when the visual system doesn’t have all the information its needs.
Consider the “Cornsweet effect” (Purves et al., 1999). If we look at the following scene, we perceive that the gray patch above the white rectangle has the same luminance as the gray patch below the white rectangle.
However, if we fill in the white rectangle with a rounded contour and transition in luminance, our perception changes. We believe the light source must be coming from above, and that it is shining more directly on the upper surface than the lower surface. Yet, because the amount of light that hits our retina from the upper surface and lower surface is the same, we assume that the upper surface is inherently darker than the lower surface. That is, we imagine that if we were to shine a light directly on the two surfaces, the upper surface would appear darker than the lower one.
Our perception is influenced by assumptions that our visual system makes about the light source and reflectance of the materials.
This is what is going on in “the dress,” except that our uncertainty is in the chromatic nature of the illuminating light. Is the illuminating light daylight, which contains a broad range of component colors ranging from blue to red? Or is it an artificial light source, which usually contains much higher percentages of green, yellow and red light?
An object that looks white when illuminated by daylight will reflect more yellow light when it is illuminated by a yellowish light source, simply because of the color of the light that’s being shone on it. However, if we know that the light source is yellow-dominated, and we have some objects in the room that allow us to guess that the light source is yellow-dominated, then our brain will “correct” the raw data it is receiving and we will still perceive the object as white.
Now let’s consider an object that looks blue when illuminated by daylight. When it is illuminated by a yellowish light source, it will still reflect the weak blue light that is present in the yellowish light source, and it will also reflect some weak yellow light simply because the object is getting hit with a lot of yellow light. That is, in terms of “raw data,” our eyes will collect light more broadly across the spectrum — blues, greens, yellows and reds. If we have cues that tell us that the light source is yellow-dominated, we will still see the object as blue.
If we see a blue object illuminated by yellow-dominated light but for some reason our brain thinks that it is actually illuminated by daylight, our brains will perceive the object as white.
The dress illusion is strong because the light source is ambiguous. Some people might imagine that the dress is being illuminated by daylight, and they will perceive the material as white. Others may think it is under strong artificial illumination, and the material will appear blue.
From moment to moment, our impression can change, but we always have a single impression.
It looks pink to me.
This story was written by Stephen Van Hooser.
Update: Rosa Lafer-Sousa at MIT has combined the dress image with images from Beau Lotto that evoke strong sensations of yellow-dominated or blue-dominated illuminating light. Separately zoom in on both images. See if you can see the dress as blue or white in the different figures! http://web.mit.edu/bcs/nklab/what_color_is_the_dress.shtml
Want renewable energy? There’s an enzyme for that.
It’s all about those enzymes.
Enzymes are nature’s magicians. They perform incredibly complicated feats of chemistry in milliseconds. They change light and food into energy, carbon dioxide into oxygen, one cell into two. They are responsible for catalyzing — speeding up — every biological process. If researchers could replicate the power, speed and efficiency of nature’s enzymes, it could mean true renewable energy, not to mention new drugs and greener industrial materials.
There has been some progress in engineering enzymes — think ethanol and other biofuel fuels — but enzymes designed in a lab still can’t compete with those evolved in nature. This is partly because researchers haven’t had a clear, step-by-step understanding of how enzymes do their magic.
Now, we do.
For the first time, Brandeis University researchers have observed and recorded each step of how the enzyme adenylate kinase (ADK), catalyzes the transfer of energy in our cells. Dorothee Kern, professor of biochemistry and Howard Hughes Medical Institute Investigator, published the findings in a recent issue of Nature Structural and Molecular Biology.
ADK plays an important role in cellular energy homeostasis, maintaining the right nucleotide (chemical energy storage molecules) levels in cells. Kern and her team, which included professor Michael Hagan, outlined the minimum five-step process of catalysis, during which the sophisticated ADK enzyme binds the target nucleotides, closes around them, catalyzes the chemical reaction, reopens and releases the final product. The whole process takes milliseconds with the enzyme. Without it, it would take about 8,000 years for this process to happen naturally.
The team also observed what each part of the enzyme does during the process — revealing an efficient team of players, including magnesium, each responsible for multiple parts of catalysis.
“We found that you really can’t get much more efficient than ADK,” Kern says. “It really is an amazing accelerator.”
Kern’s work is a first step to designing better, faster, stronger enzymes but there is still a long way to go.
“The first step is seeing how it works in nature,” Kern says. “Then, we can figure out how to make it better.”
This work was supported by the Howard Hughes Medical Institute, the Office of Basic Energy Sciences, Catalysis Science Program, Department of Energy and the National Institutes of Health.
Evolution may hold the key to rational drug design
This is the story of Abl and Src — two nearly identical protein kinases whose evolution may hold the key to unlocking new, highly specific cancer drugs.
Abl and Src are bad guys — oncogenes with a predilection to cause cancer in humans, mainly chronic myeloid leukemia (CML) and colon cancer. These two proteins are separated by 146 amino acids, and one big difference — Abl is susceptible to the cancer drug Gleevec, while Src is not.
Dorothee Kern, professor of biochemistry and Howard Hughes Medical Institute investigator, unraveled the journey of these two proteins over one billion years of evolution, pinpointing the exact evolutionary shifts that caused Gleevec to bind well with one and poorly with the other. This new approach to researching enzymes and their binding sites may have a major impact on the development of rational drugs to fight cancer.
The findings were published in the journal Science and coauthored by Doug Theobald, professor of biochemistry, with Christopher Wilson, Roman Agafonov, Marc Hoemberger, Steffen Kutter, Jackson Halpin, Vanessa Buosi, Adelajda Zorba, Renee Otten and David Waterman.
When Gleevec hit the market in 2001, it was hailed as the magic bullet against cancer.
That’s because most cancer drugs fight a scorched-earth campaign — killing as many healthy cells as cancerous ones. But Gleevec is specifically attracted only to Abl, the enzyme in cancerous cells responsible for growth and reproduction. Gleevec binds with Abl, deactivating it and stopping the spread of cancer in its tracks.
Developing more drugs to work like Gleevec — known as rational drug design —could create therapies that target specific enzymes in many types of cancer. Unfortunately, scientists haven’t known why Gleevec is so picky, binding with Abl but not with its close cousin Src.
To solve this puzzle, Kern and her team turned back the evolutionary clock one billion years to find Abl and Src’s common ancestor, a primitive protein in yeast they dubbed ANC-AS. They mapped out the family tree, searching for changes in amino acids and molecular mechanisms.
“Src and Abl differ by 146 amino acids and we were looking for the handful that dictate Gleevec specificity,” says Kern. “It was like finding a needle in a haystack and could only be done by our evolutionary approach.”
As ANC-AS evolved in more complex organisms, it began to specialize and branch into proteins with different regulation, roles and catalysis processes — creating Abl and Src. By following this progression, while testing the proteins’ affinity to Gleevec along the way, Kern and her team were able to whittle down the different amino acids from 146 to 15 responsible for Gleevec specificity.
These 15 amino acids play a role in Abl’s conformational equilibrium — a process in which the protein transitions between two structures. The main difference between Abl and Src, when it comes to binding with Gleevec, is the relative times the proteins spend in each configuration, resulting in a major difference in their binding energies.
By understanding how and why Gleveec works on Abl — and doesn’t work on Src — researchers have a jumping off point to design other drugs with a high affinity and specificity, and a strong binding on cancerous proteins.
“Understanding the molecular basis for Gleevec specificity is opened the door wider to designing good drugs,” says Kern. “Our results pave the way for a different approach to rational drug design.”
This research was supported by HHMI, the Office of Basic Energy Science, the U.S. Department of Energy Catalysis Science Program and grants from the National Institutes of Health.
Why all-nighters don’t work
Want to ace that test tomorrow? Here’s a tip: Put down the coffee and hit the sack.
Scientists have long known that sleep, memory and learning are deeply connected. Most animals, from flies to humans, have trouble remembering when sleep deprived, and studies have shown that sleep is critical in converting short-term into long-term memory, a process known as memory consolidation.
But just how that process works has remained a mystery.
The question is, does the mechanism that promotes sleep also consolidate memory, or do two distinct processes work together? In other words, is memory consolidated during sleep because the brain is quiet, allowing memory neurons to go to work, or are memory neurons actually putting us to sleep?
In a recent paper in the journal eLife, graduate students Paula Haynes and Bethany Christmann in the Griffith Lab make a case for the latter.
Haynes and Christmann focused their research on dorsal paired medial (DPM) neurons, well-known memory consolidators in Drosophila. They observed, for the first time, that when DPM neurons are activated, the flies slept more; when deactivated, the flies kept buzzing.
These memory consolidators inhibit wakefulness as they start converting short-term to long-term memory. All this takes place in a section of the Drosophila brain called the mushroom body, similar to the hippocampus, where our memories are stored. As it turns out, the parts of the mushroom body responsible for memory and learning also help keep the Drosophila awake.
“It’s almost as if that section of the mushroom body were saying ‘hey, stay awake and learn this,’” says Christmann. “Then, after a while, the DPM neurons start signaling to suppress that section, as if to say ‘you’re going to need sleep if you want to remember this later.’”
Understanding how sleep and memory are connected in a simple system, like Drosophila, can help scientists unravel the secrets of the human brain.
“Knowing that sleep and memory overlap in the fly brain can allow researchers to narrow their search in humans,” Christmann says. “Eventually, it could help us figure out how sleep or memory is affected when things go wrong, as in the case of insomnia or memory disorders.”
To learn more about this and other fly research, check out Christmann’s blog, Fly on the Wall.
This research was funded by the National Institute of Health.
An Overwhelming Sense of Discovery
Jose Vargas ’15 is a time traveler.
As an undergraduate researcher in professor John Wardle’s lab, Vargas studies quasars, the brightest and most remote objects in the universe, clocking in at 10 to 12 billion light years away, meaning Vargas is looking 10 to 12 billion years in the past.
Quasars form when supermassive black holes — billions of times the mass of the Sun — feed on nearby material. The matter forms an accretion disk around the black hole, heating up to millions of degrees and blasting out radiation and powerful jets of particles, traveling at nearly light speed — like the universe’s largest particle colliders.
Astrophysicists believe that quasars may be an important step in the birth of galaxies.
We asked Vargas to describe what it’s like to see into the past. Here is what he said:
Big news for little cilia
Take a deep breath. You just inhaled dust, dirt, pollen, bacteria and probably more than a few of these dust mites — but don’t worry, your cilia are on it.
Cilia, the cell’s tails and antennae, are among the most important biological structures. They line our windpipe and sweep away all the junk we inhale; they help us see, smell and reproduce. When a mutation disrupts the function or structure of cilia, the effects on the human body are devastating and sometimes lethal.
The challenge in diagnosing, studying and treating these genetic disorders, called ciliopathies, is the small size of cilia — about 500-times thinner than a piece of paper. It’s been difficult to examine them in molecular detail until now.
Professor Daniela Nicastro and postdoctoral fellow Jianfeng Lin have captured the highest-resolution images of human cilia ever, using a new approach developed jointly with Lawrence Ostrowski and Michael Knowles from the University of North Carolina School of Medicine. They reported on the approach in a recent issue of Nature Communications.
About 20 different ciliopathies have been identified so far, including primary ciliary dyskinesia (PCD) and polycystic kidney disease (PKD), two of the most common ciliopathies. They are typically diagnosed through genetic screening and examination of a patient’s cilia under a conventional electron microscope.
The problem is, conventional electron microscopy is not powerful enough to detect all anomalies in the cilia, even when genetic mutations are present. As a result, the cause of ciliary malfunctions can be elusive and patients with ciliopathies can be misdiagnosed or undiagnosed.
Nicastro and her team developed an approach that includes an advanced imaging technique that entails rapidly freezing human samples to preserve their native structure, imaging them with transmission electron microscopy, and turning those images into 3D models. This cutting-edge imaging was in part made possible by the advanced instrumentation in the Louise Mashal Gabbay Cellular Visualization Facility at Brandeis. It is the first time this approach has been used on human cilia and patient samples.
We have a new window into the structure and defects in human cilia, says Nicastro.
“For so long, researchers haven’t been able to see the small defects in human cilia,” Nicastro says. “Now, we can fill in the pieces of the puzzle.”
The hunt for dark matter (and other fun physics in 2015)
There may not be an equation to prove it — but 2015 promises to be a big year for Brandeis physics.
In 2015, the Large Hadron Collider at CERN — the world’s largest science experiment — will reboot after two years of upgrades, with double the energy of its first run. The Brandeis High Energy Physics Group will be in the thick of it, exploring the newly discovered Higgs boson and hunting for supersymmetry, dark matter and extra dimensions.
With its National Science Foundation Grant renewed for six years at $12 million, The Brandeis Bioinspired Soft Materials Research Science and Engineering Center (MRSEC) will enter a new phase in 2015. Led by physicist Seth Fraden, the interdisciplinary group will continue its groundbreaking research into active biological matter and membranes materials, paving the way for soft robotics, novel drug delivery systems and artificial cells.
Over the next year, the Brandeis Astrophysics Group will continue its exploration of the cosmos, peering deep into the cores of galaxies and quasars, while Brandeis theorists continue to unravel the mysteries of quantum entanglement and gravity.
Expect new ideas and directions in undergraduate education as well, says professor Jané Kondev, physics department chair. In 2014, Kondev received a $1 million grant from The Howard Hughes Medical Institute to bolster interdisciplinary undergraduate research at Brandeis.
In 2015, physics professor Zvonimir Dogic and biology professor Melissa Kosinski-Colllins will begin collaborating on a new first-year lab course for premeds and life-science students, focusing on the physics of living systems.
Whether you’re interested in dark matter or active matter, 2015 promises to be an exciting year. Stay tuned!