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. 

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.