Venturing Out of the Lab to Defend Science

It’s 6 p.m. on a Wednesday and the grad students aren’t at their lab benches. IM softball doesn’t start till next week, what gives?

We’ve snuck out of our labs a bit early to take in a dose of U.S. policy for the evening.

Politics fall far outside our normal areas of expertise. I’m a biology Ph.D. student studying plants — even with my liberal arts education, politics isn’t my bread and butter.

Buz Waitzkin of Science & Society (blue shirt) gave grad students a highly accelerated intro to matters of science policy.

But the current political climate in the U.S. has many scientists taking a more careful look into politics. Being scholars who have a sense of the world around us has become more important than ever.

“Agency regulation, funding, it’s all decided by our branches of government,” says Ceri Weber, a 3rd year Ph.D. candidate in Cell Biology.

Weber, a budding “sci-pol” enthusiast and the general programming chair for the student group INSPIRE, feels passionately about getting scientists informed about policy.

So she organized this event for graduate scientists to talk with the deputy director of Duke Science & Society, Buz Waitzkin, who previously served as special counsel to President Bill Clinton, and now teaches science policy classes cross-listed between Duke’s Biomedical Science programs and the Law School.

Seated with food and drinks—the way to any grad student’s heart—we found ourselves settling in for an open discussion about the current administration and the impact its policies could have on science.

We covered a lot of ground in our 2-hour discussion, though there was plenty more we would love to continue learning.

We discussed: lobbying, executive orders, the balances of power, historical context, tradition, and civil actions, to name a few.

There were a lot of questions, and a lot of things we didn’t know.

Even things as simple as “what exactly is a regulation?” needed to be cleared up. We’ve got our own definition in a biological context, but regulation takes on a whole new meaning in a political one. It was neat having the chance to approach this topic from the place of a beginner.

We were floored by some of the things we learned, and puzzled by others. Importantly, we found some interesting places of kinship between science and policy.

When we discussed the Congressional Review Act, which impacts regulations—the main way science policy is implemented—we learned there is ambiguity in law just like there is in science.

One area on all of our minds was how we fit into the picture. Where can our efforts and knowledge as scientists and students can make a difference?

I was shocked to learn of the lack of scientists in government: only five ever in Congress, and three in the Cabinet.

But luckily, there is space for us as science advisors in different affiliations with the government. There are even Duke graduate students working on a grant to develop science policy fellowships in the NC state legislature.

At the end of the night, we were all eager to learn more and encouraged to participate in politics in the ways that we can. We want to be well-versed in policy and take on an active role to bring about change in our communities and beyond.

Hopefully, as the years go on, we’ll have more opportunities to deepen our knowledge outside of science in the world around us. Hopefully, we’ll have more scientists who dare to step out of the lab.

Guest Post by Graduate Student Ariana Eily

Cells Need Their Personal Space

One of the body’s first lines of defense against harmful pathogens is the skin. The constant maintenance of this epithelial cell layer which serves as a barrier to infection  is essential to fighting off disease.

Jody Rosenblatt, an Associate Professor in the Department of Oncological Sciences at the University of Utah School of Medicine, has made it her lab’s mission to study the function of epithelia as a barrier, how this barrier is maintained, and what happens when it goes awry.

Jody Rosenblatt, PhD is an investigator for the Huntsman Cancer Institute at the University of Utah School of Medicine and a Howard Hughes Medical Institute Faculty Scholar

Rosenblatt recently spoke at Duke’s Developmental & Stem Cell Biology Colloquium where she presented some extraordinary findings about how epithelia can squeeze out  both healthy and dying cells  to preserve the protective barrier.

Some c cells commit suicide via programed cell death and are forced out of the cell layer because they are no longer functional. But in the case of forcing out living cells, “cell extrusion is more like a homicide” said Rosenblatt. The fact that perfectly functional living cells are pushed out of a cell layer perplexed her group until they discovered it was happening as a response to cell overcrowding.

Rosenblatt explained that like people, cells tend to like their personal space, so when this is compromised, live cells are actively pushed out of the cell layer, restoring balanced cell numbers.

Rosenblatt’s lab took this discovery a step farther and pinpointed the pathway that likely induces the extrusion of live cells.

Piezo1, a stretch-activated calcium ion channel present in epithelial cells, senses crowding and activates sphingosine-1-phosphate (S1P), the driver of epithelial cell extrusion. When Piezo1 channels are inhibited and don’t sense stretching, cells cannot extrude.

Using zebrafish, Rosenblatt showed that when extrusion was blocked by compromising the S1P2 pathway, epidermal cells form masses that are resistant to chemotherapy drugs and signals for programmed cell death.

Rosenblatt explains the importance of regulating cell extrusion in the epithelium to maintain the tissue’s function as a protective barrier for our organs. Misregulation of this function can result in diseases such as metastatic cancers.

This finding lead them to examine samples of human pancreatic, lung, colon, and breast tumors. They found that in all of these cancers, S1P2 is significantly reduced. But if they restored S1P2 activity in cell lines of these cancers, the extrusion pathway was rescued and tumor size and metastases were greatly decreased!

Rosenblatt and her colleagues have shown that the importance of cell extrusion cannot be overstated. If extrusion is compromised, cells can begin to pile up and move beneath the cell layer, which can lead to invasion of the tissues beneath the epithelium and metastasis to other sites in the body.

Now that we are uncovering more of the pathways involved in tumor formation and metastasis, we can develop new drugs that may be the key to fighting these devastating diseases.

Guest Post by Amanda Cox, PhD candidate in biology

 

Totally Tubular! Fluid forces that affect the development of biological tubes

Have you ever wondered how something as simple as fluid can impact the development of a large organism? How about the way tubes form in relation to each other? Or maybe you’ve wondered how it is possible for something as rigid as a spine to be formed from fluid?

Zebrafish embryos are relatively transparent, making them easier to study.

Zebrafish embryos are relatively transparent, making them easier to study.

Dr. Michel Bagnat and his lab work to analyze each of these questions and more in their research about how biological tubes are formed and how pressure exerted by these fluids affects the formation of these tubes.

Dr. Bagnat, an associate professor of cell biology, uses ‘forward genetics,’ a process by which genes are modified in order to see the effect and function of each gene in the organism. The technique enables them to identify and analyze the role of fluid secretion in zebrafish. Fluid secretion also plays a role in many human diseases, including cystic fibrosis and polycystic kidney disease.

The void in a blood vessel is called the lumen. Bagnat studies the cells lining the lumen.

The void in a blood vessel is called the lumen. Bagnat studies the cells lining the lumen.

One of the most interesting aspects of tubal formation is that biological tubes often form in relation to each other. Dr. Bagnat and his lab study this type of tubal formation through studying the lumen, or the thin membrane lining the intestinal tubes of zebrafish. There are many cellular mechanisms that can affect the formation of the lumen, and extensive research is conducted in order to better understand these mechanisms.

These same sorts of forces can even help build a structure as complex as the spine. Dr. Bagnat’s research covers this specific field. The notochord of zebrafish, or the scaffold which will develop into a spine, is heavily affected by the growth of vacuoles, or fluid-filled sacs in the cell. Dr. Bagnat’s research explores the deeper mechanisms behind the filling of these fluid vacuoles in cells and how each cell’s vacuole stops and starts filling with fluid.

This image of fluid-filled sacs forming a fish notochord was on the cover of a journal.

This image of fluid-filled sacs forming a fish notochord was on the cover of a journal.

Overall, Dr. Bagnat’s research holds strong implications for how we understand the development and formation of biological tubes not just in zebrafish but in our own human bodies.

Guest Post by Vaishnavi Siripurapu, North Carolina School of Math and Science, Class of 2018

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Treating Traumatic Brain Injury

After a traumatic brain injury (TBI), the brain produces an inflammatory response. This prolonged swelling is known as cerebral edema and can be fatal. Unfortunately, the only medications available just address symptoms and cannot directly treat the inflammation.

Daniel Laskowitz

Daniel Laskowitz, M.D. M.H.S, is a professor of neurology.

Some people can walk out okay after suffering from this injury, yet others can become comatose or may even die. This raises the intriguing question: why do people with similar injuries end up with vastly different outcomes? TBI affects nearly 2 million Americans every year and nearly 52,000 of these injuries are fatal.

“To a certain extent, the way the body responds to injury is probably genetically hardwired,” said Dr. Daniel Laskowitz, a neurologist at Duke who has been working on the mysteries of traumatic brain injuries for two decades. He said in medical school, he preferred the approach of treating the whole body and not super specializing. He chose to work specifically with brain injury because he could treat patients with other conditions along with brain injury.

One of Dr. Laskowitz’s first publications was about brain injury. As a fellow training in neurology in the mid-1990s, he looked at genetic factors that could make a difference in the outcome of a brain injury and found that genetic variation in a protein called apolipoprotein E (apoE) played a role.  ApoE comes in three slightly different flavors, and one of the common forms of apoE (apoE4) was associated with bad outcomes after brain injury. This raised the question of what apoE was doing in the brain to affect outcome after injury.

In 1997, he published an article about the effect of apoE on mice suffering a stroke and found that mice with the apoE allele had a better recovery than mice with an apoE deficiency. These findings were later repeated in an article in 2001,which found that following traumatic brain injury, animals with apoE had better outcomes than animals without this protein.

Since it was found that apoE could improve an injured patient’s neurologic outcomes, it became a model for medication to treat brain injuries. However, apoE does not easily cross the blood-brain-barrier, making it a challenging molecule to dispense as a drug.

Dr. Laskowitz’s lab has spent almost a decade looking at how apoE works. They have recently developed a peptide made of 5 amino acids, CN-105, that is based off of this protein and is able to cross the blood-brain-barrier, giving it the potential to be distributed as a treatment. This has been tested in mice and shown to improve outcomes.

In July, CN-105  completed a first phase clinical trial and found that  drug administration was safe and well tolerated. In the coming year, a phase 2 study will look at whether  CN-105 improves outcomes in patients with brain hemorrhages.

The plan is to give the peptide through an IV every six hours for three days, the time period when most of the swelling happens after injury.

Dr. Laskowitz’s research has already had a significant impact on the treatment of brain injury, and hopefully, this new medication could be another great contribution to this field.

Ryan SheltonGuest Post by Ryan Shelton, North Carolina School of Math and Science, Class of 2017

Acoustic Metamaterials: Designing Plastic to Bend Sound

I recently toured Dr. Steven Cummer’s lab in Duke Engineering to learn about metamaterials, synthetic materials used to manipulate sound and light waves.

Acoustic metamaterials recently bent an incoming sound into the shape of an A, which the researchers called an acoustic hologram.

Acoustic metamaterials recently bent an incoming sound into the shape of an A, which the researchers called an acoustic hologram.

Cummer’s graduate student Abel Xie first showed me the Sound Propagator. It was made of small pieces that looked similar to legos stacked in a wall. These acoustic metamaterials were made of plastic and contained many winding pathways that delay and propagate, or change the direction, of sound waves. The pieces were configured in certain ways so they could design a sound field, a sort of acoustic hologram.

These metamaterials can be configured to direct a 4 kHz sound wave into the shape of a letter ‘A’. The researchers measured the outgoing sound wave using a 2D sweeping microphone that passed back and forth over the A-shaped sound like a lawnmower, moving to the right, then up, then left, etc. The arrangement of metamaterials that reconfigures sound waves is called a lens, because it can focus sound waves to one or more points like a light-bending lens.

Xie then showed me a version of the acoustic metamaterials 10 times smaller that propagated ultrasonic (40 KHz) sound waves. He told me that since 40 kHz was well out of the human range of hearing, it could be a viable option for the wireless non-contact charging of devices like phones. The smaller wave propagator could direct inaudible sound waves to your device, and then another piece of technology called a transfuser would convert acoustic energy into electrical energy.

This structure, with a microphone in the middle, can perform the "cocktail party" trick that humans can -- figuring out where in the room a sound is coming from.

This structure with a microphone in the middle can perform the “cocktail party” trick that humans can — picking out once voice among many.

Now that the waves have been directed, how do we read them? Xie directed me to what looked like a plastic cheesecake in the middle of the table. It was deep and beige and was split into many ‘slices.’ Each slice was further divided into a unique honeycomb of varying depth. The slices were separated from each by glass panes. This directed the soundwaves across the unique honeycomb of each slice towards the lone microphone in the middle. A microphone would be able to recognize where the sound was coming from based on how the wave had changed while it passed over the different honeycomb pattern of each slice.

Xie described the microphone’s ability to distinguish where a sound is coming from and comprehend that specific sound as the “cocktail party effect,” or the human ability to pick out one person speaking in a noisy room. This dense plastic sound sensor is able to distinguish up to three different people speaking and determine where they are in relation to the microphone. He explained how this technology could be miniaturized and implemented in devices like the Amazon Echo to make them more efficient.

Dr. Cummer and Abel Xie’s research is changing the way we think about microphones and sound, and may one day improve all kinds of technology ranging from digital assistants to wirelessly charging your phone.

Frank diLustro

Frank diLustro is a senior at the North Carolina School for Science and Math.

 

Using the Statistics of Disorder to Unravel Real-World Chaos

What do election polls, hospital records, and the Syrian conflict have in common? How can a hospital use a patient’s vital signs to calculate their risk of cardiac arrest in real time?

Duke statistical science professor Rebecca Steorts

Duke statistical science professor Rebecca Steorts

Statistician Rebecca Steorts is developing advanced data analysis methods to answer these questions and other pressing real-world problems. Her research has taken her from computer science to biostatistics and hospital care to human rights.

One major focus of Steorts’ research has been estimating death counts in the Syrian civil war. She is working with her research group at Duke and the Human Rights Data Analysis Group (https://hrdag.org/) on combining databases of death records into a single master list of deaths in the conflict, a task known as record linkage.

“The key problem of record linkage is this: you have this duplicated information, how do you remove it?” explained Steorts. For example, journalists from different organizations might independently record the same death in their databases. Those duplicates have to be removed before an accurate death toll can be determined.

At first glance, this might seem like an easy task. But typographic errors, missing information, and inconsistent record-keeping make hunting for duplicates a complex and time consuming problem; a simple algorithm would require days to sort through all the records. So Steorts and her collaborators designed software to sift through the different databases using powerful machine learning techniques. In 2015, she was named one of MIT Technology Review’s 35 Innovators Under 35 for her work on the Syrian conflict. She credits a number of colleagues and students for their contributions to the project, including Anshumali Shrivastava (Rice University), Megan Price (HRDAG), Brenda Betancourt and Abbas Zaid (Duke University), Jeff Miller (Harvard Biostatistics, formerly Duke University), Hanna Wallach (Microsoft Research), and Giacomo Zanella (University of Bocconi and Visitor of Duke University in 2016).

Steorts’ work towards estimating death counts in the Syrian conflict is still ongoing, but human rights isn’t the only field that she plans to study. “I think of my work as very interdisciplinary,” she said. “For me, it’s all about the applications.”

Recently, Steorts, colleague Ben Goldstein, and students Reuben McCreanor and Angie Shen have been applying statistical methods to medical data from the Duke healthcare system. Her ultimate goal is to find techniques that can be used for many different applications and data sets.

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Guest post by Angela Deng, North Carolina School of Science and Math, Class of 2017