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Daniel Dunaief

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From left, Research Assistant Onur Eskiocak, CSHL Fellow Semir Beyaz and graduate student Ilgin Ergin. Photo by Gina Motisi, 2019/CSHL.

By Daniel Dunaief

It’s a catch-22: some promising scientific projects can’t get national funding without enough data, but the projects can’t get data without funding.

That’s where private efforts like The Mark Foundation for Cancer Research come in, providing coveted funding for promising high-risk, high-reward ideas. Founded and funded by Pamplona Capital Management CEO Alex Knaster in 2017, the Foundation has provided over $117 million in grants for various cancer research efforts.

Tobias Janowitz

This year, The Mark Foundation, which was named after Knaster’s father Mark who died in 2014 after contracting kidney cancer, has provided inaugural multi-million dollar grants through the Endeavor Awards, which were granted to three institutions that bring scientists with different backgrounds together to address questions in cancer research. 

In addition to teams from the University of California at San Francisco and a multi-lab effort from Columbia University, Memorial Sloan Kettering Cancer Center and Johns Hopkins University School of Medicine, Cold Spring Harbor Laboratory scientists Tobias Janowitz and Semir Beyaz received this award.

“We are absolutely delighted,” Janowitz wrote in an email. “It is a great honor and we are excited about the work.” He also indicated that the tandem has started the first set of experiments, which have produced “interesting results.”

The award provides $2.5 million for three years and, according to Janowitz, the researchers would use the funds to hire staff and to pay for their experimental work.

Having earned an MD and a PhD, Janowitz takes a whole body approach to cancer. He would like to address how the body’s response to a tumor can be used to improve treatment for patients. He explores such issues as how tumors interact with the biology of the host.

Semir Beyaz

Semir Beyaz, who explores how environmental factors like nutrients affect gene expression, metabolic programs and immune responses to cancer, was grateful for the support of the Mark Foundation.

Beyaz initially spoke with the foundation about potential funding several months before Janowitz arrived at Cold Spring Harbor Laboratory. When the researchers, whose labs are next door to each other, teamed up, they put together a multi-disciplinary proposal.

“If the risks [of the proposals] can be mitigated by the innovation, it may yield important resources or new paradigms that can be incorporated into research proposals that can be funded by the [National Institutes of Health] and other government agencies,” Beyaz said.

Janowitz wrote that he had a lunch together in a small group with Knaster, who highlighted the importance of “high-quality data and high-quality data analysis to advance care for patients with cancer.”

Michele Cleary, the CEO of The Mark Foundation, explained that the first year of the Endeavor program didn’t involve the typical competitive process, but, rather came from the Foundation’s knowledge of the research efforts at the award-winning institutions.

“We wanted to fund this concept of not just studying cancer at the level of the tumor or tumor cells themselves, but also studying the interaction of the host or patient and their [interactions] with cancer,” Cleary said. “We thought this was a fantastic project.”

With five people on the Scientific Advisory Committee who have PhDs at the Foundation, the group felt confident in its ability to assess the value of each scientific plan.

Scientists around the world have taken an effective reductionistic approach to cancer, exploring metabolism, neuroendocrinology and the microbiome. The appeal of the CSHL effort came from its effort to explore how having cancer changes the status of bacteria in the gut, as well as the interplay between cancer and the host that affects the course of the disease.

From left, Becky Bish, Senior Scientific Director, Ryan Schoenfeld, Chief Scientific Officer and Michele Cleary, CEO of The Mark Foundation at a workshop held at the Banbury Center at Cold Spring Harbor Laboratory in September 2019. Photo by Constance Brukin.

These are “reasonable concepts to pursue, [but] someone has to start somewhere,” Cleary said. “Getting funding to dive in, and launch into it, is hard to do if you can’t tell a story that’s based on a mountain of preliminary data.”

Beyaz said pulling together all the information from different fields requires coordinating with computational scientists at CSHL and other institutions to develop the necessary analytical frameworks and models. This includes Cold Spring Harbor Laboratory Fellow Hannah Meyer and Associate Professor Jesse Gillis.

“This is not a simple task,” Beyaz said. The researchers will “collaborate with computational scientists to engage currently available state-of-the-art tools to perform data integration and analysis and develop models [and] come up with new ways of handling this multi-dimensional data.”

Cleary is confident Janowitz and Beyaz will develop novel and unexpected insights about the science. “We’ll allow these researchers to take what they learn in the lab and go into the human system and explore it,” she said.

The researchers will start with animal models of the disease and will progress into studies of patients with cancer. The ongoing collaboration between CSHL and Northwell Health gives the scientists access to samples from patients.

With the Endeavor award, smaller teams of scientists can graduate to become Mark Foundation Centers in the future. The goal for the research the Foundation funds is to move towards the clinic. “We are trying to join some dots between seemingly distinct, but heavily interconnected, fields,” Beyaz said.

Beyaz has research experience with several cancers, including colorectal cancer, while Janowitz has studied colorectal and pancreatic cancer. The tandem will start with those cancers, but they anticipate that they will “apply similar kinds of experimental pipelines” to other cancer types, such as renal, liver and endometrial, to define the shared mechanisms of cancer and how it reprograms and takes hostage the whole body, Beyaz said. 

“It’s important to understand what are the common denominators of cancer, so you might hopefully find the Achilles Heel of that process.”

While Cleary takes personal satisfaction at seeing some of the funding go to CSHL, where she and Mark Foundation Senior Scientific Director Becky Bish conducted their graduate research, she said she and the scientific team at the foundation were passionate to support projects that investigated the science of the patient.

“No one has tried to see what is the cross-talk between the disease and the host and how does that actually play out in looking at cancer,” said Cleary, who earned her PhD from Stony Brook University. “It’s a bonus that an institution that [she has] the utmost respect for was doing something in the same space we cared” to support.

The CSHL research will contribute to an understanding of cachexia, when people with cancer lose muscle mass, weight, and their appetite. Introducing additional nutrition to people with this condition doesn’t help them gain weight or restore their appetite.

Janowitz and Beyaz will explore what happens to the body physiologically when the patient has cachexia, which can “help us understand where we can intervene before it’s too late,” Cleary said.

The CSHL scientists will also study the interaction between the tumor and the immune system. Initially, the immune system recognizes the tumor as foreign. Over time, however, the immune system becomes exhausted.

Researchers believe there might be a “tipping point” in which the immune system transitions from being active to becoming overwhelmed, Cleary said. People “don’t understand where [the tipping point] occurs, but if we can figure it out, we can figure out where to intervene.”

Scientists interested in applying for the award for next year can find information at the web site: https://themarkfoundation.org/endeavor/. Researchers can receive up to $1 million per year for three years. The Mark Foundation is currently considering launching an Endeavor call for proposals every other year.

 

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Pexel photo

By Daniel Dunaief

Daniel Dunaief

What do we do when we meet someone new in 2021 IRL, or, to the 12 uninitiated readers, “in real life?”

Well, for starters, we can’t and shouldn’t shake hands. That ritual is probably long gone. Maybe the Japanese were right with bowing. If handshakes are out, hugs, even for those we might have been speaking to for months during the isolated pandemic, are absolutely forbidden.

If we can’t hug grandma, grandpa and other relatives we’ve known most or all of our lives, we certainly can’t hug, even casually, someone new.

Ideally, we’d stand somewhere between six and 60 feet away from them, especially if we’re inside. That could be problematic for people who can’t hear all that well and who don’t have the benefit of reading anyone’s lips anymore. 

In fact, I’m thinking of going into the business of selling those Mission Impossible voice changers. If you’ve seen the movies, you know that the Tom Cruise teams can change their voices to sound like everyone else. Most of us who have heard our own voices on voicemail would like a few moments to sound more like James Earl Jones or Scarlett Johansson. Maybe we like our own voice, but we’d prefer to have a British, Australian or New Zealand accent. We could change our accents, the way we change the navigational voice on Siri and ask people if they know where we’re pretending we were raised.

Now, what we discuss is a bit tricky in the hypersensitive, polarized world of 2021. Someone who’s walking a dog most likely would be happy to talk about their four-footed companion. 

I’ve been surprised by the type of questions and information people seek when they talk about my dog. People have asked not only how old he is, but also how much he weighs, as if dogs around his size are in some kind of modeling contest. Fortunately, my dog doesn’t seem particularly concerned about his weight, as he demonstrates regularly with a feverish appetite for everything from broccoli to french fries to cat vomit. Yes, he eats cat vomit, which means that if I cook something he won’t eat, he thinks it tastes worse than cat vomit, a notion that delights my teenage children.

Now, if you’re thinking about politics, you probably should keep that to yourself. Unless someone is wearing a MAGA hat or has some version of Dump Trump on a T-shirt, it’s tough to know where they stand on the plate tectonic sized political divide.

We can talk about sports, but we run the risk of someone telling us how irrelevant sports is in the modern world during a pandemic or how they wish they could return to the age when sports mattered.

Children seem like fair game, although we have to watch out for many age-related minefields. 

My son, for example, is a senior in high school. Some parents are happy to tell you all the colleges that accepted and rejected their children, while others are content to share what city or even what coast intrigues their progeny, as in, “yes, my son has only applied to schools on the East Coast or in states with fewer than seven letters” (there are nine states in that category, by the way).

So, where does that leave us in the strange world where we’re all putting on masks before we go into a bank (imagine taking a time machine from 1999 and seeing those entering a bank without masks getting into trouble?) Well, the weather is often safe, as are dogs, the disruption the pandemic caused and, generally speaking, children.

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Illustration depicting Falcatakely amid nonavian dinosaurs and other creatures during the Late Cretaceous in Madagascar. (Credit: Mark Witton)

By Daniel Dunaief

Dromomeron and Falcatakely lived nowhere near each other. They also lived millions of years apart, offering the kind of evolutionary pieces to different puzzles that thrill paleontologists.

Left, Alan Turner holds a model of the maxilla of Falcatakely, with a CT reconstruction on his computer screen.

These two creatures, the first a three-foot long dinosaur precursor discovered in Ghost Ranch, New Mexico, and the second a crow-sized bird fossil discovered in Madagascar, have taken center stage in recent scientific circles.

What they have in common is Alan Turner, Associate Professor in the Department of Anatomical Sciences at the Renaissance School of Medicine at Stony Brook University.

The discoveries, which were made over a decade ago, were recently parts of publications in consecutive issues of the prestigious journal Nature. “It’s really exciting,” Turner said. “I definitely feel fortunate” to contribute to these two publications.

Turner, who is not the lead author in either study, emphasized that these papers were only possible through teamwork. “These large, collaborative efforts are one of the ways these really significant discoveries can happen,” he said.

The work that includes Dromomeron, in particular, is one that “any one of our groups couldn’t have done [alone]. It hinged on a series of discoveries across multiple continents.”

Each paper helps fill out different parts of the evolutionary story. The Dromomeron discovery helps offer an understanding of a major evolutionary transition from the Triassic Period, while the Falcatakely find offers a look at the diversification of birds during the Cretaceous Period.

Dromomeron

Starting with the paper in which Dromomeron appears, researchers used a collection of dinosaur precursor fossils to study a smaller group of animals called lagerpetids, whose name means “rabbit lizard” or “rabbit reptile.”

These creatures lived during the age of the earliest relatives of lizards, turtles and crocodylians.

Above, a reconstruction of a pterosaur, a lagerpetid from the Triassic Period/Rodolfo Nogueria

Pterosaurs, which have a characteristic elongated fourth finger that forms a large portion of their wing, lived 160 million years ago, which means that the earlier, flightless lagerpetids roamed the Earth about 50 million years before pterosaurs.

Turner discovered Dromomeron in Ghost Ranch, New Mexico 14 years ago. Since then, other scientists have unearthed new bones from this prehistoric rabbit lizard group in North America, Brazil, Argentina and Madagascar.

Scientists involved in this paper used micro-CT scans and 3D scanning to compare lagerpetid and pterosaur skeletal fossils to demonstrate overlaps in their anatomy. The shape and size of the brain and inner ear of these lagerpetid fossils share similarities with pterosaurs.

The inner ear, Turner explained, is particularly important for animals like the pterosaur, which likely used it the way modern birds do when they are in flight to help determine their location in space and to keep their balance.

Lagerpetids, however, didn’t fly, so paleontologists aren’t sure how these ancient rabbit lizards used their inner ear.

Turner said the Dromomeron discovery was initially more of a curiosity. In fact, when researchers found it, “we had a blackboard in this collection space where we were working,” Turner recalled. “It was unceremoniously referred to as ‘Reptile A.’ There weren’t a lot of things to compare it to. At that point we knew we had a thing but we didn’t know what it was.”

A colleague of Turners, Randall Irmis, Chief Curator and Curator of Paleontology, Associate Professor of Geology and Geophysics at the University of Utah, traveled to Argentina, where he noticed a creature that was similar to the find in New Mexico.

Irmis’s trip “allowed our team to confirm our comparison [between Dromomeron and Lagerpeton] first-hand. From there, we were able to build out the larger evolutionary context,” Turner explained in an email.

Falcatakely

Meanwhile, Turner and Patrick O’Connor, Professor of Anatomy and Neuroscience at Ohio University and lead author on the study, shared their discovery of a bird they located in Madagascar that they called Falcatakely.

The bird’s name is a combination of Latin and Malagasy, the language of the island nation of Madagascar, which means “small scythe” and describes the beak shape.

Right, an artist reconstruction of the Late Cretaceous enantiornithine bird Falcatakely forsterae with its unique beak/Sketch by Mark Witton

The scientists found a partial skull in a quarry in Madagascar. The fossil was embedded in rocks. Turner and O’Connor analyzed it through CT scanning and through careful physical and digital preparation by their colleague Joe Groenke, laboratory coordinator for the O’Connor lab.

The discovery of grooves on the side of the face for a beak took the researchers by surprise.

“As the face began to emerge from the rock, we immediately knew that it was something very special, if not entirely unique,” O’Connor said in a press release. 

“Mesozoic birds with such high, long faces are completely unknown, with Falcatakely providing a great opportunity to reconsider ideas around head and beak evolution in the lineage leading to modern birds.”

As with the Dromomeron find, the discovery of Falcatakely didn’t provide a eureka moment when the scientists found it 10 years ago.

“We didn’t know [what we had] when we collected this material,” Turner said. “It wasn’t until we CT scanned the block in an effort to begin the preparation that we said, ‘Wait a second. There’s something really weird in this block. The flat part turned out to be the side of the face.”

Turner originally thought it could have been the breast bone of a larger dinosaur. During the pandemic, he has come back to projects that have been sitting around for several years. Some have “probably danced on the periphery that have now come to the dance,” in terms of his focus.

In looking back on the ingredients that made these two Nature papers possible, Turner added another element. These publications underline “the importance of investing in long term field work expeditions,” he said.

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Photo from Pixabay

By Daniel Dunaief

Daniel Dunaief

For my family and me, the pandemic-triggered life change started almost exactly 10 months ago, on March 13. How different is the life we lead now from the one we led way back in March? Comparing answers to the same questions then and now can offer a perspective on the time that’s passed and our current position.

Question: What do we do?

March 2020: Shut businesses down, encourage people to stay home and track everything. Talk about where we are “on the curve” and hope that we can “flatten the curve” and reach the other side, allowing us to return to the lives and habits we used to know.

January 2021: Try to keep infection rates down and take measured chances in public places, while hoping officials allow schools, restaurants and other businesses to remain open.

Question: What do we eat?

March 2020: Pick up take out food whenever we can. Go to the grocery store and cook. Baking rapidly became a release and relief for parents and children, who enjoyed the sweet smell of the house and the familiar, reassuring and restorative taste of cookies and cakes.

January 2021: In some places, we can eat indoors. Many people still order take out or cook their own food.

Question: What do we do with our children?

March 2020: Overburdened parents, who are conducting zoom calls, conference calls and staring for hours at computer screens, face the reality of needing to educate their children in subjects they either forgot or never learned.

January 2021: Many students continue to go to school, even as the threat of closing, particularly in hot spots, continues.

Question: What do we do for exercise?

March 2020: People take to the streets, order exercise equipment or circle the inside or outside of their house countless times, hoping to break free from their blinking, beeping and demanding electronic devices.

January 2021: Gyms have reopened, with some people heading to fitness centers and others continuing their own version of counting the number of times they’ve circled the neighborhood, with and without their dogs.

Question: What can we do about work?

March 2020: Many businesses close, asking employees to work from home.

January 2021: Many businesses are trying to stay open, even as others have continued to ask their employees to work from home, where they can talk on computer screens in mismatched outfits, with nice blouses and shirts on top and gym shorts or pajamas.

Question: What can we plan for?

March 2020: We cancel weddings, parties, family gatherings and all manner of events that involve crowds.

January 2021: We have learned not to make plans that are set in stone, because the calendar has become stone intolerant. We make plans and contingency plans.

Question: What do we do for entertainment?

March 2020: We secretly binge watch TV shows, although we don’t share our indulgences.

January 2021: After we ask how everyone is doing, we regularly interject questions about the latest TV shows or movies.

Question: What do we notice in the supermarkets?

March 2020: Toilet paper and paper towels are hard to find.

January 2021: Toilet paper and paper towels are generally available, but we may only be allowed to buy two packages. The cost of paper goods and other items seems to have risen.

Question: Do we let our children play sports?

March 2020: Almost every league in every sport shut down, following the lead of professional teams.

January 2021: Youth leagues have restarted.

Question: What’s a cause for optimism?

March 2020: We believe in flattening the curve.

January 2021: The vaccine offers hope for a return to a life we used to know.

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Michael Schatz and Aspyn Palatnick. Photo by Lauryl Palatnick

By Daniel Dunaief

Michael Schatz, Adjunct Associate Professor at Cold Spring Harbor Laboratory, saw some similarities to his own life when he met the then 14-year old Aspyn Palatnick.

Palatnick, who was a student at Cold Spring Harbor High School, had been developing games for the iPhone. When he was that age, Schatz, who is also a Bloomberg Distinguished Associate Professor of Computer Science and Biology at Johns Hopkins University, stayed up late into the evening programming his home computer and building new software systems.

Meeting Palatnick eight years ago was a “really special happenstance,” Schatz said. He was “super impressed” with his would-be young apprentice.

When he first met Schatz, Palatnick explained in an email that he “realized early on that he would be an invaluable mentor across research, computer science, and innovation.”

Palatnick was looking for the opportunity to apply some of the skills he had developed in making about 10 iPhone games, including a turtle racing game, to real-world problems.

Knowing that Palatnick had no formal training in computer science or genetics, Schatz spent the first several years at the white board, teaching him core ideas and algorithms.

“I was teaching him out of graduate student lecture notes,” Schatz said.

Schatz and Palatnick, who graduated with a bachelors and master’s from the University of Pennsylvania and works at Facebook, have produced a device which they liken to a “tricorder” from Star Trek. Using a smart phone or other portable technology, the free app they created called iGenomics is a mobile genome sequence analyzer.

The iPhone app complements sequencing devices Oxford Nanopore manufactures. A mobile genetic sequencer not only could help ecologists in the field who are studying the genetic codes for a wide range of organisms, but it could also be used in areas like public health to study the specific gene sequences of viruses like SARS-CoV-2, which causes COVID-19.

In a paper published in GigaScience, Schatz and Palatnick describe how to use iGenomics to study flu genomes extracted from patients. They also have a tutorial on how to use iGenomics for COVID-19 research.

While developing the mobile sequencing device wasn’t the primary focus of Schatz’s work, he said he and others across numerous departments at Johns Hopkins University spent considerable time on it this summer, as an increasing number of people around the world contracted the virus.

“It very rapidly became how I was spending the majority of my time,” said Schatz.

Palatnick is pleased with the finished product.

“We’ve made DNA sequence analysis portable for the first time,” he explained in an email.

Palatnick said the app had to use the same algorithms as traditional genomics software running on supercomputers to ensure that iGenomics was accurate and practical. Building algorithms capable of rendering DNA alignments and mutations as users tapped, scrolled and pinched the views presented a technical hurdle, Palatnick wrote.

While Schatz is optimistic about the vaccinations that health care workers are now receiving, he said a mass vaccination program introduces new pressure on the virus.

“We and everyone else are watching with great interest to see if [the vaccinations] cause the virus to mutate,” Schatz said. “That’s the big fear.”

Working with the sequences from Nanopore technology, iGenomics can compare the entire genome to known problematic sequences quickly. Users need to get the data off the Oxford Nanopore device and onto the app. They can do that using email, from Dropbox or the web. 

In prior viral outbreaks, epidemiologists traveled with heavier equipment to places like West Africa to monitor the genome of Ebola or to South and Central America to study the Zika virus genome.

“There’s clearly a strong need to have this capability,” Schatz said.

Another iGenomics feature is that it allows users to airdrop any information to people, even when they don’t have internet access.

Schatz urged users to ensure that they use a cloud-based system with strong privacy policies before considering such approaches, particularly with proprietary data or information for which privacy is critical.

As for COVID-19, people with the disease have shown enough viral mutations that researchers can say whether the strain originated in Europe or China.

“It’s kind of like spelling mistakes,” Schatz said. “There are enough spelling mistakes where [researchers] could know where it came from.”

Palatnick described iGenomics as an “impactful” tool because the app has increased the population of people who can explore the genome from institutional researchers to anyone with an iPhone or iPad.

In the bigger picture, Schatz is broadly interested in learning how the genome creates differences.

“It’s important to understand these messages for the foods we eat, the fuels we use, the medicines we take,” Schatz said. “The next frontier is all about interpretation. One of the most powerful techniques is comparing one genome to another.”

Schatz seeks out collaborators in a range of fields and at numerous institutions, including Cold Spring Harbor Laboratory.

Schatz and W. Richard McCombie, Professor at CSHL, are studying the genomes of living fossils. These are species that haven’t evolved much over millions of years. They are focusing on ancient trees in Australia that have, more or less, the same genetic make up they did 100 million years ago.

As for Palatnick, Schatz described his former intern and tricorder creating partner as a “superstar in every way.” Schatz said it takes considerable fortitude in science, in part because it takes years to go from an initial idea on a napkin to something real.

Down the road, Schatz wouldn’t be surprised if Palatnick took what he learned and developed and contributed to the founding of the next Twitter or Facebook.

“He has that kind of personality,” Schatz said.

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Photo from Pixabay
Daniel Dunaief

I have brought three fictional characters in to discuss their thoughts for 2021. Please welcome Yoda from the “Star Wars” series, Jack Ryan from Tom Clancy books, and Jane Craig from the film “Broadcast News.” I will call you all by your first names. Well, except for you, Yoda.

TBR: After such a tumultuous 2020, I wanted to ask you what you all thought would likely happen next year.

Yoda: Tough to say, the future is. If the answers you don’t like, the questions you must change.

Jack: Look, I’m not sure what we’re doing here, but I think the vaccine offers real hope for change. Your world, such as it is, should be able to move in the right direction.

Jane: The trends at this point are horrific. You have enormous numbers of positive tests each day, hospitalizations are up and the number of dead continues to rise.

TBR: Yoda, you’re kind of off point and sound like a backwards fortune cookie. Jack, I appreciate the optimism and Jane, I think you’re focusing on the negatives.

Jane: We can’t preclude the possibility that the positive infections will continue to climb for months. While it’d be swell to have a big party to celebrate the vaccine and the return to whatever version of normal each of us has, it’s important that we protect ourselves and our families.

Jack: She’s right. Everyone doesn’t have the vaccine and everyone hasn’t taken it, which means we won’t reach herd immunity for a while. While this is killing the entertainment industry, among so many others, it’s necessary for us to sit tight for a while. At the same time, we need to consider the possibility that other governments will become opportunistic about this messy transition at the White House. We need to protect ourselves and remain vigilant. This is a dangerous time, in so many ways, and we need to analyze all kinds of traffic.

Yoda: Know something about vigilance, do I. Messy, this world has become. Goodness, hope and optimism, there remains. Effort to get there will it take.

TBR: Jane, this question, in particular, seems right up your alley. What do you think about the news business in 2021?

Jane: I’m not going to lie to you, it’s been a tough year for everyone, particularly in the news business. We are not the enemy. When we do our jobs well, people get to hear the truth. They can make informed decisions that affect their lives. Are there problems? Of course, but that doesn’t make the entire industry corrupt, any more than it would in any other business.

Yoda: Inside each of us, the enemy resides. Confront it, we must.

Jack: I’ve dealt with journalists all the time. They are a competitive group, I’ll give them that, but they are necessary to shine light, at the right time, on everything from the fight against the virus to the battle against corrupt governments.

TBR: Do you think we’ve learned any lessons from 2020?

Jack: It’s been a brutal year and so many people have lost so much. The numbers don’t tell the entire story. We can only live with what we know: we can protect ourselves and our family through policies that have nothing to do with politics. Careful analysis and science brought us the vaccines. We need to make informed decisions about using them.

Jane: Exactly my point, Jack. We can and should make informed decisions, which the media, at its best, can support.

Yoda: Mistakes, everyone makes. Opportunities to learn, we have. Family and those fortunate enough to share life with us, we must cherish.

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Carlos Simmerling

By Daniel Dunaief

They know what happens. They’re just not sure how it happens.

Carlos Simmerling, Marsha Laufer Endowed Professor of Physical and Quantitative Biology and Professor of Chemistry at Stony Brook University, has spent over 22 years trying to answer the question of how processes at a molecular level occur.

Using chemistry, physics and computer programs he helped create, Simmerling determines the intermediate structural changes that occur with biomolecules such as nucleic acids and proteins, which would be extremely difficult to impossible to do at a bench or in a laboratory.

In March, as the United States was in the beginning of various school and office lockdowns in response to the spread of the pandemic, Simmerling endured the same discomfort and loss of control.

Researchers at Brookhaven National Laboratory, including Kerstin Kleese van Dam, Director of the Computational Science Initiative, reached out to Simmerling to see if his lab might use their experience and tools to understand the spike protein on the coronavirus that causes COVID-19.

Except for two people who were on the cusp of finishing their PhD’s, everyone else in the lab “shifted to work on this instead. We put everything else on hold and it’s been nonstop since March.”

Simmerling said he and his lab group decided at a special lab meeting on March 13th that it was important to contribute whatever they could to this unprecedented crisis.

Without the same kind of restrictions or limitations that lab groups that depend on working at a bench or conducting in-person experiments might have, the Simmerling group could work every day, forging ahead to understand the way the protein operates and to look for critical steps or weaknesses that might assist doctors down the road.

Recently, Simmerling and his lab group exchanged emails over Thanksgiving, during which the group felt this commitment to COVID research gave them a “shared purpose” and helped them feel as if they were “doing something.”

While the Simmerling lab appreciated the opportunity to contribute to efforts to combat COVID-19, they also recently received a national award in high-performance computing. Called the Gordon Bell Special Prize, the award recognizes “outstanding research achievement towards the understanding of the COVID-19 pandemic through the use of high-performance computing.”

The award, which was announced at the virtual SuperComputing 2020 Conference and recognizes the work of the Simmerling lab and some collaborators they worked with since early in the pandemic, includes a $10,000 prize.

The kind of research Simmerling and his team conducted may help either with this specific virus or with any others that might threaten human health again.

“We were not well prepared in science and humanity in general,” Simmerling said. “We have to come up with better tools.”

While he is pleased that pharmaceutical companies are getting closer to introducing vaccines for COVID-19, Simmerling said any such solutions would apply to this specific virus and not to any subsequent forms of coronavirus or other potential threats to human health.

People who contracted SARS or MERS, which are coronavirus cousins, didn’t develop an immunity to COVID-19.

“Even if we all get vaccinated, that won’t help us for the next one, and we’ll likely have other ones,” Simmerling explained. “Science needs to do a better job getting deeper into how these work.”

At this point, the models Simmerling and his staff have created are working and are providing the kind of clues that could contribute to providing suggestions for future experiments. The lab is “now at the stage where we are seeing new things not seen in the experiments and suggesting new experiments to test our hypotheses,” said Simmerling.

His lab has focused on the dynamics of proteins and other biomolecules to see how they move around in time. He simulates the shape changes when molecules interact, including in the 2000s when he worked on proteins in the human immunodeficiency virus.

Simmerling likens the study to the process of shaking other people’s hands. When two people come together, their hands adapt to each other when they interact, changing shape as they move up and down.

With the spike protein in COVID-19, scientists have seen what it looks like before it interacts. The structure after it unlocks the cell is fuzzier and scientists aren’t sure if they are relevant to the actual virus or something vaguely similar to it.

“We only get snapshots at the beginning and the end,” he said. “What we need to do is figure out how it works.”

He uses software his lab has developed with a few other labs in the country. Scientists around the world use this Amber system. They take steps in time and calculate the forces on the atom, which requires millions of iterations.

Simmerling said other people sometimes think he and his team download the structure, plug it into a computer, run it and then publish a paper. That’s far from the case, as the computer does the number crunching, but people like Simmerling spend considerable time trying to understand a molecule like the spike protein well enough to develop ideas about how it might move and change.

Simmerling took a circuitous route to the world of using chemistry and physics on a computer. When he entered college at the University of Illinois at Chicago, he wanted to be a chemist. The only problem was that he didn’t enjoy working in the lab with all the chemicals.

Half way through his college education, he left school and started working at a computer company. Eight years later, he decided to return to college, where he planned to earn his chemistry degree.

“When I went back to school, I told my [teaching assistant] that I wish I could do [chemistry] on computers rather than experiments,” Simmerling said. “He introduced me to the professor [Ron Elber] who became my PhD advisor. That brought together things I was interested in.”

He knew programming and how to use computers.

“Sometimes, you’re the sum of your choices,” Simmerling said.

He and his wife Maria Nagan, who also does computer modeling at Stony Brook University, live in Port Jefferson. In non-pandemic times, Simmerling enjoys sailing throughout the year.

As for the prize, Simmerling said the “recognition is nice” and he would like his lab to contribute to “models to change how we combat infectious disease.”

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Pixabay photo

By Daniel Dunaief

Daniel Dunaief

What if James Bond had to wear a mask? What would it look like and would it become a fashion accessory and a multi-functional gadget at the same time?

It could be all black to match his dapper tuxedo. If he ever wore a bow tie that was a different color, he could coordinate the two items to keep the visual integrity of the ensemble.

Then again, maybe it’d be pink with a small ribbon, to show that he’s finally caught up to the times and, after all those years of leading ladies who fall in love with him at their own peril, he sees an opportunity to show his appreciation for women and the fight against breast cancer.

Maybe the mask would have a bright light built into it. He could use the light to interrogate someone, to shine it in someone’s eyes who was about to shoot him or to distract a vicious dog or lion that was about to eat him, but who followed the light around the room instead. He could also use the light in dark tunnels or underneath pyramids.

A problem with masks, even the ones we change each day, is that they don’t change what our faces do beneath them. It’s hard to sense the difference between a hidden smile and a smirk.

Remember those mood rings, which changed color depending on how we were feeling? A modern Bond could have a mood mask.

A James Bond mask wouldn’t simply be colorful. It would also be a communicator, akin to Maxwell Smart’s shoe in “Get Smart.” By tilting his head once to the right, Bond could speak with M or Q or any other one-letter person or, perhaps, another 00 like him, who would be able to speak with him through their mask. Tilting his head twice to the right would hang up the phone. He could dial by touching his tongue to a keypad in his mask.

By tilting his head to the left once, Bond could order a vodka martini, shaken not stirred, from the nearest bar.

In fact, keeping up with modern times, maybe Bond wouldn’t need to speak at all, but the mask could pick the ideas in his head, like, “hey, that woman over there looks intelligent. I can’t wait to speak with her about her hopes and aspirations. After we get to know each other well, we can establish a trusting relationship and then blow stuff up, kill some bad people, save the world and then spend some time undercover, if you know what I mean.”

A James Bond mask would also be the modern version of his all-purpose watch. Contoured to his face, he could whistle, causing the mask to break glass by releasing a supersonic sound. It could also shoot out a lifesaving dart or even provide oxygen for him if he were trapped underwater by a bad guy who didn’t realize that you can’t drown Bond while he’s wearing his mask.

Given the physical demands of the job, the mask would also come with a built-in coolant. Instead of sweating into the mask, the mask would be made of a dry-fit material while, on cue, it would release a comfortable and sweet-smelling coolant that would also cover up his bad breath.

Maybe he’d have a mask that played the theme song from his movies. Each time he bit down, he could sway and swagger to the familiar and engaging theme, annoying the evildoers with a song that almost always signals a Bond victory.

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Dennis Plenker Photo by Bob Giglione, 2020/ CSHL

By Daniel Dunaief

If the job is too easy, Dennis Plenker isn’t interested.

He’s found the right place, as the research investigator in Cold Spring Harbor Laboratory Cancer Center Director Dave Tuveson’s lab is tackling pancreatic cancer, one of the more intractable forms of cancer.

Plenker joined Tuveson’s lab in 2017 and is the technical manager of a new organoid facility.

Organoids offer hope for a type of cancer that often carries a poor prognosis. Researchers can use them to find better and more effective treatments or to develop molecular signatures that can be used as a biomarker towards a specific treatment.

Scientists can take cells from an organoid, put them in miniature dishes and treat them with a range of drugs to see how they respond.

The drugs that work on the organoids offer potential promise for patients. When some of these treatments don’t work, doctors and researchers can continue to search for other medical solutions without running the risk of making patients ill from potentially unnecessary side effects.

“Challenges are important and there is a sweet spot to step out of my comfort zone,” Plenker explained in an email.

Dennis Plenker Photo by Bob Giglione, 2020/ CSHL

In an email, Tuveson described Plenker as a “pioneer” who “likes seemingly impossible challenges and we are all counting on him to make breakthroughs.”

Specifically, Tuveson would like Plenker to develop a one-week organoid test, where tissue is processed into organoids and tested in this time frame.

Organoids present a cutting edge way to take the modern approach to personalized medicine into the realm of cancer treatments designed to offer specific guidance to doctors and researchers about the likely effectiveness of remedies before patients try them.

Plenker and others in Tuveson’s lab have trained researchers from more than 50 institutions worldwide on how to produce and use organoids.

“It’s complicated compared to conventional tissue culture,” said Plenker, who indicated that considerably more experience, resource and time is involved in organoid work. “We put a lot of effort into training people.”

Tuveson explained that the current focus with organoids is on cancer, but that they may be useful for other conditions including neurological and infectious diseases.

The way organoids are created, scientists such as Plenker receive a biopsy or a surgical specimen. These researchers digest the cells with enzymes into singular cells or clumps of single cells and are embedded. Once inside the matrix, they form organoids.

When they “have enough cells, we can break these down and put them into multi-well plates,” Plenker explained. In these plates, the scientists test different concentrations and types of drugs for the same patient.

It’s a version of trial and error, deploying a range of potential medical solutions against cells to see what weakens or kills cells.

“If you do that exercise 100 times, you can see how many times compound A scores vs. C, E and F. You get a sense of what the options are versus what is not working,” Plenker said.

While scientists like Plenker and Tuveson use targeted drugs to weaken, cripple or kill cancer, they recognize that cancer cells themselves represent something of a molecular moving target.

“There is a very dynamic shift that can happen between these subtypes” of cancer, Plenker said. “That can happen during treatment. If you start with what’s considered a good prognosis, you can end up with a higher fraction of basal cancer cells” which are more problematic and have a worse prognosis. “We and others have shown that you have a mixture of cell types in your tumor all the time.”

Part of what Plenker hopes to discover as the director of the organoid center is the best combination of ingredients to foster the growth of these versatile and useful out-of-body cancer models.

The gel that helps the cells grow is something Plenker can buy that is an extracellular matrix rich matter that is of murine, or rodent, origin. He hopes to develop a better understanding of some of these proprietary products so he can modify protocols to boost the efficiency of the experiments.

Plenker is “trying to innovate the organoids, and so he may need to adjust conditions and that would include inventing his own recipes,” Tuveson explained.

The facility, which received support from the Lustgarten Foundation, will engage in future clinical trials.

The type of treatments for pancreatic cancer patients typically fall into two arenas. In the first, a patient who is doing well would get an aggressive dose of chemotherapy. In the second, a patient who is already sick would get a milder dose. Determining which regimen is based on the current diagnostic techniques.

Plenker and his wife Juliane Dassler-Plenker, who works as a post-doctoral fellow in the lab of Mikala Egeblad at Cold Spring Harbor Laboratory, live in Huntington. The pair met in Germany and moved to the United States together.

Plenker calls himself a “foodie” and appreciates the hard work that goes into creating specific dishes.

In his career, Plenker always “wanted to help people.” He has appreciated the latest technology and has disassembled and put back together devices to understand how they work.

Prior to the pandemic, Plenker had gone on short trips to Germany to visit with friends and relatives. He is grateful for that time, especially now that he is much more limited in where he can go. He appreciates his landlord and a second American family which helps the couple feel welcomed and grateful.

In 2017, Plenker recalls attending a talk Tuveson gave in Washington, D.C. in which he invited anyone in the audience who wanted to improve a test to come and talk to him after the presentation.

“I was the only one in that regard who talked to him” after that lecture, Plenker said.

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By Daniel Dunaief

Daniel Dunaief

My wife wanted to get out of the house and move beyond the daily walk in our neighborhood for her birthday. We decided to take our teenage children to the zoo.

Back when our son and daughter were younger, a trip to the zoo was a cause for celebration, as they got to see animals from all over the world, watch various shows, spend about four seconds reading an interesting fact about their favorite creature, and continue to hop, skip and jump from one exhibit to the next.

These days, their thumbs do most of the hopping, skipping and jumping. Given the importance of birthdays in our house and the willingness to do whatever the birthday celebrant desires, our teenagers gamely climbed into the car.

As with most zoos this year, we had to preregister for tickets. Indeed, the Bronx Zoo requires visitors to use a date-specific ticket.

The experience of entering the zoo was remarkably quick and smooth, saving us the customary wait.

Zoos require guests to remain socially distanced and to wear masks. All but about eight of the other visitors we saw wore masks.

Most of the time, other guests also maintained social distancing, taking their turns to the glass to look at gorillas and apes, who didn’t seem at all curious about the appearance of people whose lips and noses disappeared behind masks.

While we circumnavigated the walking trail, all four of us reveled in the appearance of numerous animals, including an enormous bison and a swaying elephant.

It seemed slightly unfair to the ostrich, who is over nine feet tall and is the largest bird in the world, to share a pen with the 20-foot giraffe, which dwarfs a bird that also has the largest eye of any bird in the world.

Something about seeing all these animals, including a lemur resting in a tree, an arctic fox and a pair of lions, restored a sense of normalcy in an abnormal year. It was also comforting to hear the excitement from other people who all expressed similar sentiments in several languages when the giraffe started to run.

On our first trip out around the zoo, we stopped at three bear exhibits in which the celebrated occupants were either not there or hidden. Once we had circled the zoo and headed back towards the car, my wife played her birthday privilege, urging us to take one more look at the black bear, the grizzly bear, and the polar bear.

The first two bears remained out of view on our way back to the car. Standing alone along the railing at almost exactly 4 p.m., which was closing time, we saw the polar bear slowly emerge, then retreat, then emerge from a darkened den. We suspected he might have a keen sense of time and know when it as safe to come out and avoid  larger crowds.

He or she (we didn’t read anything about the bear’s gender) played with a toy that looked like the top of a garbage can and then reached up to a ledge to pull down a bone with some meat on it. After giving us an eight-minute private show, the polar bear took his bone and, as if on cue, exited stage right.

While the zoo might not be at the top of your list or top of mind, particularly during the winter, it offers a pleasant chance to get away from our own 2020 pens. The Bronx Zoo has a know before you go page, which you can see by searching Know Before You Go — Bronx Zoo, with details about visiting this year.

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