There is no rule that says scientists have to look or act a certain way. Scientists can be funny and outgoing, athletic and artistic. They come from all different backgrounds and have all different interests. At Brandeis, our scientists are as diverse as the groundbreaking research they engage in. This on-going series is inspired by This is What a Scientist Looks Like.
This post was written by Madelen Díaz, PhD student in professor Michael Rosbash’s lab.
The music of the mind
Where are you from?
I was born and raised in Miami, Fla. after my parents emigrated from Cuba.
What do you research?
I currently research the neuronal circuitry responsible for circadian rhythm in the fruit fly (Drosophila melanogaster). Why do we use the fruit fly to study circadian rhythm? Fruit flies sleep at night and even sleep the siesta during the afternoon. Several of the molecular proteins responsible for these behavioral oscillations are conserved across species. We use complex genetic tools, behavioral assays, and several imaging techniques to see how these circadian neurons coordinate with each other to produce their active/sleep cycle throughout the day.
What is your biggest passion outside of science?
My passion outside of science has always been classical piano. I’ve been playing since I was 6 years old. There is something incredibly relaxing about immersing yourself into the music that you forget that ever-growing “to-do” list.
How do you define discovery, and how does it make you feel?
I would term discovery as obtaining an unexpected or controversial result. It’s very exciting thinking of the possibilities of a new discovery and how this can potentially contribute to the “big picture.” It can also be nerve-wracking because of the uncertainty of not knowing what to do next or where to look. The most difficult part of graduate school is to continue working through all of the uncertainty.
What do you do to unwind, after a long day at the lab?
After a long day in the lab, I most commonly relax by baking desserts or playing piano. On weekends, I like to go out salsa dancing or traveling New England.
That’s how Elyn Saks, law professor and mental health advocate, describes the delusions, hallucinations, memory loss and mental fragmentation that schizophrenia causes.
The mental disorder affects millions of people worldwide but the cause of its wide-ranging symptoms remains largely unknown.
At Brandeis University, researchers believe they have discovered an abnormality in the schizophrenic brain that could be responsible for many of the disease’s symptoms and could provide a drug target for therapeutic treatments.
Led by John Lisman, the Zalman Abraham Kekst Chair in Neuroscience and professor of biology, and Matthew Wilson of MIT, the research team published their findings in a recent issue of the Journal of Biological Psychiatry. The paper was co-authored by Aranda Duan, Carmen Varela, Yuchun Zhang, Yinghua Shen, Lealia Xiong, and Matthew Wilson.
Unusual neural oscillations — brain waves — have long been associated with schizophrenia. The oscillations, called delta waves, are similar to slow oscillations seen in normal brains during sleep, but in schizophrenic brains, they occur during wakefulness. The connection between these oscillations and schizophrenic symptoms, particularly cognitive deficits such as memory impairment, has long been unclear.
Lisman and his team set out to understand that connection by artificially producing delta waves in mammalian brains using a new technique called optogenetics, which activates brain signals using light.
When the delta frequency light was turned on, Lisman observed disruption in the working memory of rats. When it was turned off, the rodents were once again able to perform working memory tasks. More important, Lisman and his team were able activate the abnormal oscillations only in a tiny subpart of the thalamus, a region of the brain that has long been a focus of schizophrenia research.
An information hub and relay center, the thalamus is central to working memory, sleep, consciousness and sensory-information processing.
“The oscillations produce an artificial signal that jams normal communication,” Lisman says. “The part of the thalamus that is supposed to carry information about working memory couldn’t do the task at all with these sleep-like delta waves. We suspect the abnormal delta oscillations seen in patients with schizophrenia are producing a similar jamming of normal signals.”
Delta waves require a specific type of ion channel called a T-type Ca channel. These channels are of particular interest because they are one of the few types of ion channel implicated in schizophrenia by genetic studies. The next step, Lisman says, is to figure out what kind of agents could be used to block these channels.
“If you could block these channels, you could block these bad oscillations,” he says. “That may have therapeutic value in patients.”
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 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?
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.
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.”
We like to think of evolution as a fine-tuning process, one that whittles away genetic redundancies in pursuit of that elusive goal first articulated by Victorian intellectual Herbert Spencer: becoming “the fittest” species. The only problem is, we are not fine-tuned machines. Our bodies are chock-full of parts that either don’t work anymore (talking to you, appendix) or are so buggy that our biology has Macgyvered a way to make it work.
Take our DNA. No, seriously, take our DNA. It’s mostly garbage anyways. Fifty percent of our genome is comprised of genetic parasites, called transposable elements or transposons, that usually lie dormant. When they are allowed to move around the genome, they can wreak havoc on our genes. These bundles of rogue DNA sequences, nicknamed jumping genes, can hop into an essential gene and interrupt it, leading to a variety of mutations that cause conditions like infertility.
The woman who discovered transposons, Barbara McClintock, won the Nobel Prize in Physiology or Medicine, and is the only woman to receive an unshared Nobel in that category.
Our reproductive cells, called germ cells, are particularly sensitive to transposons, so they rely on a system called the PIWI pathway to keep the transposons in check. Scientists have long wondered how the pathway works and why, despite its checks and balances, do transposons still make up such a large portion of our genome. Understanding the system would help scientists demystify human infertility and other diseases that result when transposons run amok.
Brandeis biology professor Nelson Lau and his lab recently published two studies on the PIWI pathway, short for P-element Induced Wimpy testis. When the pathway is blocked in fruit flies, it results in small, infertile testes and ovaries.
The pathway’s main weapons against transposons are PIWI proteins and small RNA molecules called piRNAs.
Think of PIWI proteins as transposon bounty hunters and piRNAs as the wanted posters that provide vital information about the outlaw DNA. But the piRNAs don’t offer a complete picture. “Germ cells do something very weird by shredding that wanted poster into a lot of small pieces,” Lau says. “Instead of carrying the whole poster, piRNAs carry what might look like part of a nose, half of an eye or a sliver of a lip.”
Just as a shredded wanted poster could match many faces, those small piRNAs could match many good genes, so how do PIWI proteins track down and silence transposons without silencing good genes in the process?
In a study published in RNA, Lau and his team, led by graduate student Josef Clark and former technician Christina Post, observed that PIWI proteins are careful. The proteins waited until they had a good composite picture from enough piRNAs before they clamped down on the transposon.
But that doesn’t mean the system is flawless. Far from it, Lau’s team discovered.
In a second study published in Genome Research, Lau and postdocs Yuliya Sytnikova, Reazur Rahman and bioinformatician Gung-wei Chirn observed new transposable elements in the fruit fly cells moving to different areas of the genome, affecting nearby genes. “We all knew that the PIWI pathway was continuously active, so the conventional wisdom was that it was doing a decent job keeping these transposons under wraps,” Lau says. “We stood corrected.”
It turns out transposons are not so easily subdued. Many slipped past the PIWI system, landing on new genome spots and impacting surrounding genes. Some transposons could even make disguises — long non-coding RNAs that Lau thinks are meant to trick the PIWI proteins.
This may explain why transposons continue to make up such a large part of our genome, Lau says. “The PIWI pathway works just well enough to allow our germ cells to develop, but not well enough to keep all of the transposons fully redacted,” he says.
This may seem an ineffective way to protect our genome — our body’s most important artifact — but there may be a method in PIWI’s madness. After all, transposons have evolved with every member of the animal kingdom, from sponges to humans — there must be some reason they’re tolerated.
Perhaps, Lau says, a bit of genetic mischief, in the right places, is good. It ensures genetic variation and diversity, which is important for a species to reproduce and evolve.
Like so much of our biology, it’s not pretty but it is effective — for the most part.
Scientifically speaking, there is no bad DNA, though we like to blame it for unruly hair, klutziness or poor gardening skills. There is, however, junk DNA.
Heterochromatin are tight bundles of DNA that often contain the genes our cells want to keep quiet, either because they are not needed or they are repetitive. Heterochromatic genes are silenced by a muzzle-like protein while the gene cells we want expressed, called euchromatin, are activated.
Sometimes, an important gene — a gene we want activated — gets mistakenly embedded in junk DNA. Scientists have long wondered how those genes get activated. Now, Brandeis University researchers may have solved that mystery.
Michael Marr, associate professor of biology, published a paper in the journal Molecular and Cellular Biology this summer with John Lis of Cornell University, Jessica Treisman of the NYU School of Medicine and former Brandeis research associate Sharon Marr, now at the Massachusetts General Hospital.
Transcription of DNA into RNA is an insanely complicated process that is still not entirely understood. In the 1990s, Roger Kornberg, a professor of structural biology at Stanford University, discovered a huge, multiprotein complex he called Mediator, which helps activate transcription. Kornberg won the Nobel Prize for his discovery.
Mediator, which is present in every eukaryotic organism from yeast to humans, is composed of dozens of subunits. However, some of the subunits are found only in animal cells. One of these subunits, Med26, has long been thought to be a marker for active, euchromatin genes.
Yet Marr and his colleagues discovered Med26 in heterochromatin — the first time the subunit has been observed among inactive genes. Either Med26 is moonlighting in an entirely new role, says Marr, or it is there tracking down lost genes and activating them.
“It looks as though Med26 is tethered to the silencer and maybe activates essential genes that got lost in the junk pile,” Marr says.
Marr and his team studied Med26 in Drosophila, the first time the subunit has been studied in an intact animal model. The team discovered that while cells and organs can develop without Med26, the organism as a whole dies if the subunit is removed.
“Med26 is essential for multicellular life and is involved in both active and silent genes,” Marr says. “Exactly how is the next big question.”
Ever had that dream where you’re about to take a test or perform in a play or go to a job interview and you are completely, woefully unprepared?
Many of us have that classic nightmare when we’re stressed out. But, for the scientists who study the effect of stress on the body, recreating those unnerving situations in real life is an important part of their research, however sadistic it may sound.
Psychology professor Nicolas Rohleder and his team of graduate and undergraduate researchers use so-called stress tests to study interleukin-6 (IL-6), an inflammatory agent linked to stress and a known contributor to heart disease, diabetes and cancer.
The science of stressing people out has, thankfully, evolved over the years from early tests in which participants were asked to stick their hands in buckets of ice or forced to watch videos of bloody surgeries, to more humane procedures today.
Although stress and its impact on the body have been studied since Austrian-Canadian endocrinologist Hans Selye’s experiments in the 1930s, stress tests weren’t standardized until the 1990s, when Clemens Kirschbaum of the Technische Universität in Germany came up with the Trier Social Stress Test (TSST).
Instead of using ghoulish or physically shocking methods to measure stress response, the TSST is designed to trigger a stress response to a social threat.
Considered the gold standard of stress tests, it has been used around the world in thousands of studies. Rohleder’s lab alone has put more than 1,200 people through the test. Though Rohleder can’t reveal everything in the TSST — it would ruin the stress for participants — he can share the basics.
First, researchers invite participants to sit in a comfy chair in a quiet room to draw blood to establish a baseline. Of course, needles themselves are stressors for some, so researchers attempt to make the experience as relaxing as possible.
Next, participants are introduced to a team of researchers and asked to perform two different kinds of tasks. The first requires interacting with the researchers and the second requires solving a problem. Two researchers observe and time participants performing the tasks.
I know problem-solving tasks can be stressful — math certainly stresses me out. But what’s so scary about a social interaction, you might ask. Think about a time you went on a first date, or to a party where you didn’t know many people. Think about your first day of orientation at Brandeis. How did you feel? Were your palms sweaty? Was your heart beating a little faster?
As social creatures, humans need social interactions to survive, says Rohleder. But people who perform poorly in social situations risk being isolated or cast out of the group. Evolutionarily speaking, their genetic longevity may be in danger (though there are exceptions to the rule).
Obviously, researchers can’t expose subjects to life-threatening stressors, but luckily, social stressors provide the next best measure. The risk of social isolation triggers many of the same biological responses as physical threats, and the sympathetic nervous system kicks into gear, cortisol levels spike, and secondary stress systems, such as the inflammatory agent IL-6, activate.
Most of the time, by the end of the TSST, participants’ heart rates are up, they might be sweating; their adrenalin might be pumping. The test usually stresses researchers out, too, Rohleder says, since they are also in a difficult social situation.
After the test, researchers take another blood sample to measure the biochemical changes in the body caused by stress. Participants can then leave — probably to calm down over a stiff drink.
Future stress test might include social media stressors, like Twitter trolls or nasty Facebook posts but we likely won’t see that in the lab until more people start seeing it in their dreams.
To read about Rohleder’s current research, check out our story on BrandeisNow.
Working with biochemistry professor Jeff Gelles, Brandeis research scientists Larry Friedman and Johnson Chung built a novel light microscope that uses multiple laser colors to examine the behavior of individual protein, DNA and RNA molecules. The researchers tag molecules with fluorescent colors, enabling the microscope to reveal the workings of the molecular machines that control the architecture of cells and regulate genes.