On January 23, the Christina Renna Foundation (CRF), together with Cold Spring Harbor Laboratory, will host a free virtual celebration and sarcoma update to mark their 14th Annual Angel’s Wish Gala. Join us in celebrating 14 years of funding cutting edge research into rare pediatric cancer.
The gala will honor Christopher Vakoc, MD., Ph.D., Professor, Cold Spring Harbor Laboratory, 2020 CRF Research Award recipient for the Sarcoma Research Project
The Christina Renna Foundation is a 501(c)(3) public charity supporting children’s cancer research and furthering awareness and education through the support of cancer groups and outreach programs for the direct support of those in need. Funds raised through this event will go to continued research into rhabdomyosarcoma (RMS), a rare and often fatal form of pediatric cancer. In total, CRF has donated over $350,000 to research at CSHL. For more information, please visit: www.crf4acure.org
What: CRF Angel’s Wish Virtual Gala and Sarcoma Research Update
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.
Brookhaven Lab Scientist Guobin Hu loaded the samples sent from researchers at Baylor College of Medicine into the new cryo-EM at LBMS. Photo from BNL
On January 8 the U.S. Department of Energy’s (DOE) Brookhaven National Laboratory welcomed the first virtually visiting researchers to the Laboratory for BioMolecular Structure (LBMS), a new cryo-electron microscopy facility. DOE’s Office of Science funds operations at this new national resource, while funding for the initial construction and instrument costs was provided by NY State. This state-of-the-art research center for life sciences imaging offers researchers access to advanced cryo-electron microscopes (cryo-EM) for studying complex proteins as well as the architecture of cells and tissues.
Many modern advances in biology, medicine, and biotechnology were made possible by researchers learning how biological structures such as proteins, tissues, and cells interact with each other. But to truly reveal their function as well as the role they play in diseases, scientists need to visualize these structures at the atomic level. By creating high-resolution images of biological structure using cryo-EMs, researchers can accelerate advances in many fields including drug discovery, biofuel development, and medical treatments.
During the measurement of the samples, the LBMS team interacted with the scientists from Baylor College of Medicine through Zoom to coordinate the research. Photo from BNL
This first group of researchers from Baylor College of Medicine used the high-end instruments at LBMS to investigate the structure of solute transporters. These transporters are proteins that help with many biological functions in humans, such as absorbing nutrients in the digestive system or maintaining excitability of neurons in the nervous system. This makes them critical for drug design since they are validated drug targets and many of them also mediate drug uptake or export. By revealing their structure, the researchers gain more understanding for the functions and mechanisms of the transporters, which can improve drug design. The Baylor College researchers gained access to the cryo-EMs at LBMS through a simple proposal process.
“Our experience at LBMS has been excellent. The facility has been very considerate in minimizing user effort in submission of the applications, scheduling of microscope time, and data collection,” said Ming Zhou, Professor in the Department of Biochemistry of Molecular Biology at Baylor College of Medicine.
All researchers from academia and industry can request free access to the LBMS instruments and collaborate with the LBMS’ expert staff.
“By allowing science-driven use of our instruments, we will meet the urgent need to advance the molecular understanding of biological processes, enabling deeper insight for bio-engineering the properties of plants and microbes or for understanding disease,” said Liguo Wang, Scientific Operations Director of the LBMS. “We are very excited to welcome our first visiting researchers for their remote experiment time. The researchers received time at our instruments through a call for general research proposals at the end of August 2020. Since September, we have been running the instruments only for COVID-19-related work and commissioning.”
LBMS has two cryo-electron microscopes—funded by $15 million from NY State’s Empire State Development—and the facility has space for additional microscopes to enhance its capabilities in the future. In recognition of NY State’s partnership on the project and to bring the spirit of New York to the center, each laboratory room is associated with a different iconic New York State landmark, including the Statue of Liberty, the Empire State Building, the Stonewall National Monument, and the Adam Clayton Powell Jr. State Office Building.
“By dedicating our different instruments to New York landmarks, we wanted to acknowledge the role the State played in this new national resource and its own unique identity within Brookhaven Lab,” said Sean McSweeney, LBMS Director. “Brookhaven Lab has a number of facilities offering scientific capabilities to researchers from both industry and academia. In our case, we purposefully built our center next to the National Synchrotron Light Source II, which also serves the life science research community. We hope that this co-location will promote interactions and synergy between scientists for exchanging ideas on improving performance of both facilities.”
Brookhaven’s National Synchrotron Light Source II (NSLS-II) is a DOE Office of Science User Facility and one of the most advanced synchrotron light sources in the world. NSLS-II enables scientists from academia and industry to tackle the most important challenges in quantum materials, energy storage and conversion, condensed matter and materials physics, chemistry, life sciences, and more by offering extremely bright light, ranging from infrared light to x-rays. The vibrant structural biology and bio-imaging community at NSLS-II offers many complementary techniques for studying a wide variety of biological samples.
“At NSLS-II, we build strong partnership with our sister facilities, and we are looking forward to working closely with our colleagues at LBMS. For our users, this partnership will offer them access to expert staff at both facilities as well as to a versatile set of complementary techniques,” said NSLS-II Director John Hill. “NSLS-II has a suite of highly automated x-ray crystallography and solution scattering beamlines as well as imaging beamlines with world-leading spatial resolution. All these beamlines offer comprehensive techniques to further our understanding of biological system. Looking to the future, we expect to combine other x-ray techniques with the cryo-EM data to provide unprecedented information on the structure and dynamics of the engines of life.”
LBMS operations are funded by the U.S. Department of Energy’s Office of Science. NSLS-II is a DOE Office of Science user facility.
Brookhaven National Laboratory is supported by the U.S. Department of Energy’s Office of Science. The Office of Science is the single largest supporter of basic research in the physical sciences in the United States and is working to address some of the most pressing challenges of our time. For more information, visit https://energy.gov/science.
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.
Corals in the Gulf of Aqaba in the Red Sea. Photo by Maoz Fine
A paper published in Frontiers in Marine Science on December 15 is calling for action to remove the oil from a decaying and inactive tanker in the Red Sea that holds approximately one million barrels of oil – four times the amount of oil contained in the Exxon Valdez, the tanker that had a disastrous environmental oil spill in 1989 – before its current seepage turns into a massive oil spill into the sea. The paper, a policy brief, is authored by a team of international scientists led by Karine Kleinhaus, MD, MPH, an Associate Professor of the School of Marine and Atmospheric Sciences (SoMAS) at Stony Brook University.
Scientists produced a computer simulation of the spread of oil from the abandoned tanker in the Red Sea. The projection shows mass spread during winter compared to summer due to current patterns. The data shown was produced by running the model for 30 days. Oil spread even further from the tanker when the model ran for a longer period of time. Photo from SBU
Called the Safer, the tanker is a floating storage and offloading unit (FSO) abandoned for years, and with access controlled by Yemen’s Houthis. The paper, titled “A Closing Window of Opportunity to Save a Unique Marine Ecosystem,” comes shortly after The New York Times reported on November 24 that the Houthis will grant permission to a United Nations (UN) team to board the Safer to inspect and repair the vessel in the near future.
“The time is now to prevent a potential devastation to the region’s waters and the livelihoods and health of millions of people living in half a dozen countries along the Red Sea’s coast,” says Dr. Kleinhaus. “If a spill from the Safer is allowed to occur, the oil would spread via ocean currents to devastate a global ocean resource, as the coral reefs of the northern Red Sea and Gulf of Aqaba are projected to be among the last reef ecosystems in the world to survive the coming decades.”
She explained that the reason the coral reefs of the northern Red Sea are unique is because they survive in much warmer waters than today’s ocean temperatures, which are becoming too high for most coral to tolerate (over half of the Great Barrier Reef has degraded due to marine heat waves caused by climate change). Additionally, the fish living on the reefs off Yemen in the southern Red Sea are a major resource of food for the populations of the region, and the entire sea and its coral reefs are a highly biodiverse and rich ecosystem.
Dr. Kleinhaus and co-authors point out that in May 2020 seawater breached the Safer and entered the engine compartment, and news agencies have reported oil spots next to the tanker, indicating likely seepage. The tanker has been abandoned since 2015, which the authors emphasize is a long advance warning of a decaying tanker poised to degrade to the point of a mass oil leak into the Red Sea.
The paper reveals a computer model of how the oil will disperse if a major leak begins this winter. The model shows that the oil will reach much further if the spill occurs now rather than in summer, due to the typical winter currents in that region of the Red Sea. A spill now will cause much broader and more extensive devastation as a result.
Despite the signs of the Safer’s structural deterioration, access to the tanker has yet to be achieved and concrete steps to repair or to prevent an oil spill have yet to been taken, the authors point out. Dr. Kleinhaus adds that winter is the worst time to have an oil spill in that region, as winter currents will disperse oil much more widely.
The authors urge that “Emergent action must be taken by the UN and its International Maritime Organization to address the threat of the Safer, despite political tensions, as a spill will have disastrous environmental and humanitarian consequences, especially if it occurs during winter. With millions of barrels of oil, a day passing through the Red Sea, a regional strategy must be drafted for leak prevention and containment that is specific to the Red Sea’s unique ecosystems, unusual water currents, and political landscape.”
The Long Island Explorium, 101 E. Broadway, Port Jefferson has been selected by the Museum Association of New York (MANY) with 98 museums from across New York State to participate in “Building Capacity, Creating Sustainability, Growing Accessibility”, an IMLS CARES Act grant project designed to help museums impacted by the COVID-19 pandemic share their collections and reach audiences who cannot physically visit their museums. Staff will be trained to use new hardware and software to develop programs that will engage their communities and reach new audiences.
The grant is an in-depth partnership for two years designed to strengthen museum virtual programs. In addition to the training, museums will receive hardware and software equivalent to a $5,000 in-kind donation.
“We are honored to be awarded IMLS CARES act funding and excited to be able to make an impact on the work of our colleagues and their museums across New York State,” said Erika Sanger, MANY Executive Director. “We are living in an age of transition, experiencing a radical shift in our ways of learning and communicating. The group selected captures the diversity of our shared history in NY and our nation. The stories embodied in the museums’ collections and the storytelling talents of their interpretive staff are the heart of the project.”
In this two-year program, museums will identify a program to virtually deliver to their audiences, focusing on developing programs from stories found in their collections that reveal cultural and racial diversity in their communities.“We are ecstatic to receive this award to continue to be responsive and reflective of the diverse communities we aim to reach. We aim to build upon a current exhibit, “Rain Gardens: Linking Water, Wildlife, and Wisdom,” and use technology to develop a video/ audio series that focuses on the rich heritage of the indigenous peoples of Long Island and their contributions to Long Island”, said Angeline Judex, MPA, Executive Director, Long Island Explorium.
“The Long Island Explorium was selected due to our perseverance in the face of the devastating COVID-19 pandemic and our commitment to STEM and those in our communities on Long Island and in New York,” explained Lisa Collet Rodriguez, M.S. Director, Digital Media/Marketing, Long Island Explorium. “We are excited to begin working with the Museum Association of New York serving high need communities through this initiative. The program is geared to assist and successfully respond to one of the biggest challenges created by the pandemic: how we reach audiences that cannot visit the Long Island Explorium in person. The pandemic has provided the Explorium with an opportunity to re-imagine our program delivery methods and engage our online audiences through meaningful content on a much larger scale.”
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.
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.”
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.
Arkarup Banerjee is coming back home to Cold Spring Harbor Laboratory. This time, instead of working on the olfactory system, the way he did in Associate Professor Dinu Florin Albeanu’s lab from 2010 to 2016, he is studying vocalizations in the Alston’s singing mouse, a Central American rodent.
Banerjee rejoined Cold Spring Harbor Laboratory in November after almost four years of post-doctoral work at NYU Langone Medical Center. He hopes to use the study of the way these mice react to songs and the way they formulate them to understand how signals from the brain lead to vocalizations.
Singing Mouse
“The reason I decided to come back to Cold Spring Harbor Laboratory is not just because I did my PhD here,” said Banerjee, who is an assistant professor. “Neuroscience [at the lab] is amazing. I have fantastic colleagues. I expect to have lots of collaborations.” CSHL is one of his “top choices” in part because of the ability to interact with other researchers and to attend meetings and courses, he said.
To hear Albeanu tell it, CSHL’s colleagues appreciate the skill and determination Banerjee, whom Albeanu described as a “rare catch,” brings to the site.
“There was pretty much unanimous excitement about his vision for his research,” Albeanu said. “Pretty much everyone was in agreement that [hiring Banerjee] is a must.”
Fundamentally, Banerjee is interested in understanding how the brain computes information. In his new lab at CSHL, he wanted to study the natural behaviors that animals produce without having to teach them anything.
“That’s why my fascination arose in singing mice,” he said. “Nobody has to train them to vocalize.” He hopes to understand the neural circuits in the context of a natural behavior.
In the longer term, Banerjee is interested in contributing to the field of human communication. While numerous other creatures, such as birds, interact with each other vocally, singing from trees as they establish territorial dominance and soliciting mates through their songs, mice, which have cerebral cortexes, have brain architecture that is more similar to humans.
The Alston’s singing mice, which is found in the cloud forests of Costa Rica and Panama, is also different from numerous other species of mice. Many rodents produce vocalizations in the ultrasonic range. These animals can hear calls that are outside the range of human capacity to pick up such sounds.
The singing mice Banerjee is studying produces a stereotyped song that is audible to people. “These mice seem to specialize in this behavior,” he said. In neuroscience, scientists seek animals that are specialists with the hope that understanding that species will reveal how they work, he said.
Audible communications are important for male mice in attracting mates and in guarding their locations against other males. These lower-frequency sounds travel across greater distances.
Specifically, Banerjee would like to know the anatomical differences between the brains of typical rodents and the singing mice. He plans to probe “what kind of changes does it require for a new behavior to emerge during evolution.”
The songs have some value to the males who sing them. Females prefer males who sing more notes per unit time in a 10-second period.
In his experiments, Banerjee has demonstrated that the conventional view about one of the differences between humans and other vocalizing animals may not be accurate. Scientists had previously believed that other animals didn’t use their cortex to produce songs. Banerjee, however, showed that the motor cortex was important for vocal behaviors. Specifically, animals with temporarily inactivated cortexes could not participate in vocal interactions.
As a long term goal, Banerjee is also interested in the genetic sequence that makes the development of any anatomical or behavioral feature different in these singing mice. By using the gene editing tool CRISPR, which CSHL scientists employ regularly, Banerjee hopes to find specific genetic regions that lead to these unique behaviors.
Arkarup Banerjee with Honggoo Chae, a post-doctoral fellow at CSHL, from a Society of Neuroscience Meeting in 2018.
An extension of this research could apply to people with various communication challenges. Through studies of mice with different genetic sequences, Banerjee and other researchers can try to find genes that are necessary for more typical vocalizations. By figuring out the genetic differences, the CSHL scientist may one day discover what researchers could do to minimize these differences.
A resident of Mineola, Banerjee lives with his wife Sanchari Ghosh, who works at Cold Spring Harbor Laboratory press for the preprint service bioRxiv. The couple, who met in India, spend considerable time discussing their shared interest in neuroscience. Banerjee said his wife is a “much better writer” than he and has helped edit his manuscripts.
Banerjee is passionate about teaching and hopes he has a chance to educate more students once the pandemic recedes. Outside the lab, Banerjee shares an important quality with the mice he studies: he sings. He trained as a vocalist when he was growing up in India, and listens to a range of music.
Albeanu, who was teaching a course in Bangalore, India in 2009 when he met Banerjee, said it is a “pleasure to listen to [Banerjee] singing.”
Albeanu recalls how Banerjee stood out for many reasons when he first met him, including developing a way to modify a microscope.
As for his work, Banerjee hopes to understand behaviors like vocalizations from numerous perspectives. “We can seek explanations for all of these levels,” he said.
A neuroscientist by training, Banerjee would like to determine the connection between neural circuitry and the behavior it produces. “The understanding would be incomplete if I didn’t understand why this behavior is being generated.”
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