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Cold Spring Harbor Laboratory

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DNALC Assistant Director Amanda McBrien teaches a live session. Photo by Chun-hua Yang, DNALC

By Daniel Dunaief

Two letters defined the DNA Learning Center at Cold Spring Harbor Laboratory over the last several months: re, as in rethink, reimagine, reinvent, recreate, and redevelop. They also start the word reagent, which are chemicals involved in experiments.

The 32-year-old Learning Center, which teaches students from fifth grade through undergraduates, as well as teachers from elementary school to college faculty, shared lessons and information from a distance.

At the Learning Center, students typically benefit from equipment they may not have in their schools. That has also extended to summer camps. “Our camps are built on this experiential learning,” said Amanda McBrien, an Assistant Director at the Learning Center.

DNALC Educator Dr. Cristina Fernandez-Marco, teaches a Genome Science Virtual Class. Photo by Sue Lauter, DNALC

While that part of the teaching experience is missing, the center adapted to the remote model, shifting to a video based lessons and demonstrations. Indeed, campers this year could choose between a live-streamed and an on-demand versions.

Dave Micklos, the founder of the Learning Center, was pleased with his staff’s all-out response to the crisis.

“The volume of new videos that we posted on YouTube was more than any other science center or natural history museum that we looked up,” Micklos said. “It takes a lot of effort to post content if you’re doing it in a rigorous way.” During the first few months of the lockdown, the Learning Center was posting about three or four new videos each day, with most of them produced from staff members’ homes.

As for the camps, the Learning Center sent reagents, which are safe and easy to use, to the homes of students, who performed labs alongside instructors. In some camps, students isolated DNA from their own cells, plant or animal cells and returned the genetic samples to the lab. They can watch the processing use the DNA data for explorations of biodiversity, ancestry and detecting genetically modified organisms.

The Learning Center has been running six different labs this summer.

The virtual camps allowed the Learning Center to find a “silver lining from a bad situation” in which students couldn’t come to the site, McBrien said. The Learning Center developed hands-on programs that they sent throughout the country.

McBrien said the instructors watched each other’s live videos, often providing support and positive feedback. Some people even watched from much greater distances. “We had a few regulars who were hysterical,” McBrien said. “One guy from Germany, his name is Frank, he was in all the chats. He loved everything we did” and encouraged the teachers to add more scientific lessons for adults.

McBrien praised the team who helped “redevelop a few protocols” so high-level camps could enable students to interact with instructors from home.

A DNA Barcoding Virtual Camp featuring DNA Learning Center Educator Dr. Sharon Pepenella, with her virtual class. Over Pepenella’s shoulder is a picture of Nobel Prize winners Francis Crick and James Watson. Photo by Sue Lauter, DNALC.

Using the right camera angles and the equipment at the lab, the instructors could demonstrate techniques and explain concepts in the same way they would in a live classroom setting. To keep the interest of the campers, instructors added polls, quizzes and contests. Some classes included leader boards, in which students could see who answered the most questions correctly.

This summer, Micklos and Bruce Nash, who is an Assistant Director at the Learning Center, are running a citizen science project, in which teams from around the country are trying to identify ants genetically throughout the United States.

Using a small kit, one reagent and no additional equipment, contributing members of the public, whom the Learning Center dubs “Citizen Scientists,” are isolating DNA from about 500 of the 800 to 900 species of ants.

In one of the higher level classes called metabarcoding or environmental DNA research, teachers collected microbes in a sample swabbed from their nose, their knees, tap water, and water collected from lakes.

The Learning Center supports this effort for high school research through Barcode Long Island, which is a partnership with the Hudson River Park to study fish in the Hudson. High school interns and the public help with sampling and molecular biology.

“Much like barcoding, we aim to democratize metabarcoding,” Nash explained in an email. A metabarcoding workshop that ended recently had participants in Nigeria, Canada, Antigua and distant parts of the United States, with applicants from Asia.

After teaching college faculty on bar coding, Micklos surveyed the teachers to gauge their preference for future courses, assuming in-person meetings will be possible before too long.

When asked if they would like in-person instruction only, a hybrid model, or classes that are exclusively virtual, none of the teachers preferred to have the course exclusively in person. “People are beginning to realize it is more time efficient to do things virtually,” Micklos said.

Nash added that the preference for remote learning predated the pandemic.

Micklos appreciates the Learning Center’s educational contribution. “To pull these things off with basically people talking to each other via computer, to me, is pretty amazing,” he said.

Around four out of 10 students who enter college who have an interest in pursuing careers in science continue on their scientific path. That number, however, increases to six out of 10, when the students have a compelling lab class during their freshman year, Micklos said.

Lab efforts such as at the Learning Center may help steady those numbers, particularly during the disruption caused by the pandemic.

The longer-term goal at the Learning Center, Micklos said, is to democratize molecular biology with educational programs that can be done in the Congo, the Amazon or in other areas.

As for the fall, the leadership at the center plans to remain nimble.

The Learning Center is planning Virtual Lab field trips and will also continue to offer “Endless Summer” camp programs for kids and parents looking for science enrichment.

The Center also hopes to send instructors for in-person demonstrations at schools, where they can host small groups of student on site.

“We are supporting as many people as possible through our grant-funded programs and our (virtual) versions of camps and field trips,” Nash said. “These will be adapted to support schools and others to progressively improve them through the fall, with the hope of reaching all those we would normally reach.”

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John Inglis. Photo courtesy of CSHL

By Daniel Dunaief

In the post COVID-19 world, the pace of science and, in particular, scientific publishing has changed, giving researchers a sense of urgency to share information that might lead to preventions, treatments and cures.

Cold Spring Harbor Laboratory has produced two preprint research services, bioRxiv and MedRxiv, that complement the longer peer-reviewed path to publication.

After numerous scientists restructured their labs to contribute to the growing body of knowledge and information about COVID-19, these researchers turned to preprint services to share the results of their work and the evolution of their thoughts on how to defeat the virus.

“It’s absolutely unprecedented for scientists to drop what they are doing and switch their focus to something completely new to aid society and mankind in general,” said John Inglis, the co-founder of bioRxiv and one of the members of joint management group for medRxiv.

MedRxiv, which started in June of 2019, helped provide the scientific community with an outlet for their health science research, with the caveat that the results haven’t received a thorough peer review, as they might in the New England Journal of Medicine, Cell, or other periodicals.

The number of preprint research papers has climbed dramatically this year, as scientists race to get their results from the bench to the server. The number of papers in bioRxiv increased to 88,268 in June from 71,458 in January. The increase at the newer medRxiv is much more dramatic, climbing from 953 in January to 7,541 in June.

The number of pandemic related papers on medRxiv and bioRxiv in total is 6,458, with 5,133 on medRxiv and 1,325 on bioRxiv.

Pandemic-related papers account for close to 70 percent of the new research published on medRxiv since January 1st, while the percentage of virus-related papers on bioRxiv is 6.2%, in large part because bioRxiv includes numerous other subject areas, including ecology, bioinformatics, plant biology and zoology.

The world has taken notice of all these papers, with page views peaking in April for medRxiv to almost 11 million for the month.

While the papers aren’t peer reviewed, the managers of these sites urge readers to remain cautious in their interpretation and use of these findings, while the scientific community continues to duplicate any encouraging or compelling results.

“We remind people all the time that these are preprints,” Inglis said, as the site has numerous reminders about the early nature of the findings. “They are preliminary reports and should not guide clinical practice or be reported as established information. That’s a battle we’re still fighting.”

The peer review process has also picked up some speed, as journals, inundated with potential game-changing material, have been accelerating the process of reading and reviewing papers. The median time between posting an article on bioRxiv and publication in a journal before the pandemic was nine months. Some papers in medRxiv have been published in journal in as few as 35 days.

For medRxiv, the screening process requires an ethics statement, a funding statement, and any potential conflicts of interest. These requirements are “all far more familiar in medical publishing than in scientific publishing,” said Inglis.

At bioRxiv, which recently introduced a competing interest statement as well for authors, freelancers and a group of Principal Investigators look at everything before it posts, to make sure it’s science and that it’s not dangerous. The screeners turn the manuscripts back to the team if they have any concerns.

“We felt, early in the pandemic, that it was necessary to make sure we have people with expertise in outbreak science,” Inglis explained. “We brought on volunteers.”

According to Inglis, the percentage of manuscripts that scientists submit, but that bioRxiv doesn’t publish, is between 5 and 10 percent, while that figure is closer to 20 to 25 percent for medRxiv.

Inglis said numerous scientists have done some modeling based on public data, but that the preprints don’t accept those papers unless they contain additional research.

The preprint management team was “worried about the indiscriminate use of these models to guide public policy,” he said.

Additionally, the team excluded manuscripts that might be dangerous to human health or human-health related behavior. They didn’t want people to rush out and take something that, theoretically, might help, but that hasn’t received sufficient testing. A treatment might block a receptor, but also have significant side effects.

Inglis said the team of people who work at the preprints, which includes five full-time preprint-platform dedicated staff members and seven other CSHL staff with other responsibilities, including the founders, tech developers and production staff, worked seven days a week, with long working days to meet the increased need and demand.

People working on this effort “are not doing it because they are getting rich or handsomely acknowledged.” An arduous job with thousands of papers, the staff are working out of a “sense of purpose and mission,” Inglis explained.

The Chan Zuckerberg Initiative and CSHL provide financial support for these preprints. The research community has shared their appreciation for these preprints and CSHL generously acknowledges the work of the staff.

Inglis and Richard Sever co-founded bioRxiv. MedRxiv is managed by Sever and Inglis in collaboration with Professors Harlan Krumholz and Joe Ross from Yale and Dr. Theo Bloom and Claire Rawlinson from BMJ, which was originally called the British Medical Journal.

Inglis said numerous papers have become game-changers in the battle against the virus, including a study from two weeks ago in the United Kingdom on dexamethasone, a steroid that was proven effective in severe cases of COVID-19. Indeed, just recently, a Bethesda hospital became the first in the nation to use the steroid to combat the virus.

The team working in preprints at CSHL appreciates the opportunity to contribute to the public health crisis.

Inglis is pleased with how the community trusted the preprints with their work, while numerous members of the community helped screen manuscripts and provide advice about how to react to the needs of the pandemic.

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Saket Navlakha. Photo from CSHL

By Daniel Dunaief

When people walk into their own home, they immediately ignore sensory cues around them. They may not notice the picture of their children on the wall, the lush leaves of the ficus plant, or the constant smell of soup that greets them when they return from work.

Similarly, animals and even flies become accustomed to cues in their environment, habituating to them so they can focus on more important signals, like the smell of nearby food or the appearance of a fly swatter.

Cold Spring Harbor Laboratory Associate Professor Saket Navlakha and his post doctoral researcher Yang Shen recently studied the way flies subtract smells from the environment, giving them the opportunity to focus instead on odors that might be more important to their lives.

In a paper last month in the Proceedings of the National Academy of Sciences, Navlakha and Shen converted the way flies use a signal filtering process to create a computer algorithm.

Navlakha explained that the tandem were using computer science to understand better a basic biological phenomenon of habituation and how it happens. “We’ve been studying background subtraction,” he said in a recent interview.

One of the applications for their work is in electronic noses. Hotels and even military departments may in the not too distant future use these systems to process odors to determine what’s in the environment.

These electronic noses detect faint signals within noisy backgrounds. Habituation enables them to remove from consideration those scents that would otherwise distract from the goal of scanning the environment for new information.

Navlakha suggested that humans, who are often a visually dominant species, are not always the best species at using a sense of smell to perceive the environment.

Saket Navlaka with his wife Sejal Morjaria, during a run in Port Washington in mid-May. Photo by Lawrence Lau

“Many other species rely on their noses as much as we rely on vision,” he said. “We don’t always have an intuitive sense of what is possible in the olfactory space. Sometimes, that limits our imagination.”

While Navlakha is not crafting sensors that can detect compounds, he is working on the computer science analogs to odor recognition and discrimination. He is exploring the kind of data analysis that would have applications in a range of fields. 

In one example, he said a sensor in an airport might be surrounded by a symphony of smells, including new pungent or even subtle toppings on pizza or even a new cologne from someone working in a watch repair store. 

The sensor might need to sift through all that data to find someone who is transferring a toxic chemical through an airport, the scent of which might be faint and almost insignificant compared with the other odors spreading through the terminal.

In a more everyday example, a sensor in the refrigerator might detect the subtle changes in odors emitted by foods that are starting to become inedible, such as an onion or cream cheese.

“You want to detect” when food is starting to turn so you can “eat it and use it” before it becomes inedible, Navlakha said. “These are the kind of problems we are exploring on the data analysis side.”

Navlakha specifically looked at the activity of Kenyon cells, which are special odor neurons. When a fly receives a new scent, about five percent of these cells turn on, developing a unique activity tag.

Once the fly becomes habituated to a smell that isn’t relevant for its survival — either to indicate the presence of food or to announce the arrival of a predator — Navlakha believes the number of Kenyon cells that make up the tag for the odor declines. While this is his theory, he said more work needs to be done to confirm these predictions.

A new odor repeats the process, bringing the fly’s attention to a new smell. The fly brain in principal can reverse the subtraction process for habituated odors if the odor becomes more rare or important for the fly’s survival. Researchers need to conduct more work to confirm this as well.

Navlakha hopes to frame the fluid process of recognizing, habituating and bolstering the signal for odors to understand how the brain is functioning.

He said the fly brain responds to smells based on two mechanisms. In the first, the fly has an innate, evolutionary behavior. In the second, the fly learns through experience. Navlakha studied the learned behaviors.

The next steps involve pushing more on the experimental front, determining the limits of odor discrimination and looking at the role of habituation.

He hopes to extend an experiment that others have done with people. Experimenters took three odors that were all relatively similar that come from three flowers. Most people could not discriminate between two out of the three odors. In an experimental group, they allowed people to habituate to one of three smells and then they had to discriminate between the other two. By subtracting out the common part of all three smells, they were more successful at decoding the difference between the others.

“We want to see if we can do this in fruit flies” while recording from a region of the fly brain called the mushroom body.

Navlakha also bought an electronic nose. Using this artificial system, he wants to test odor discrimination algorithms.

“One thing this would allow us to do is to test and validate these algorithms to see how well they perform,” he explained. “There are all kinds of tests to see what kind of power these sensors have.”

In the PNAS paper, Navlakha mostly used the literature for their biological inspiration. They discussed numerous parts of the paper with biological collaborators and including biological experiments. They did not introduce any new biological data.

He came across this literature about 18 months ago.

“We thought it was interesting because we could understand the whole series of transformations when a fly smells,” he said. He worked on how to understand the process from input to output.

During the COVID-19 lockdown, he has been spending considerably more time doing theoretical work and modeling. He and his wife Sejal Morjaria have also gotten out of the house to do some running.

As for his work, Navlakha is hoping to build on what he’s done so far and expects he will, if you’ll pardon the pun, follow his nose as the research progresses.

 

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Bruce Stillman. Photo from CSHL

By Daniel Dunaief

Bruce Stillman, the CEO of Cold Spring Harbor Laboratory, last week won the Dr. H.P. Heineken Prize for Biochemistry and Biophysics, which is considered the most distinguished scientific prize from the Netherlands.

The prize, which has been awarded to 13 researchers who have gone on to win Nobel Prizes, includes a $200,000 award and a crystal trophy.

Stillman earned the award, which began in 1964 and is given every two years in categories including Medicine, Environmental Sciences and History, for his decades of work on mechanisms involved in the replication, or copying, of eukaryotic DNA.

The understated Stillman, who was born and raised in Australia, expects he’ll put the prize money into a foundation, although he hasn’t thought much about it given the other concerns that dominate his time, including not only running his own lab amid the COVID-19 pandemic but also overseeing a facility where he has been the Director since 1994 and its CEO since 2003.

Stillman said the lab has had “extensive discussions” among the faculty about whether to pursue additional research fields on an ongoing basis to combat the current virus as well as any future public health threats.

While CSHL is not an infectious disease center, the facility does have a historical precedent for contributing to public health efforts during a crisis. Indeed, during World War II, the laboratory helped create a mutated strain of fungus that increased its yield of the drug penicillin.

At this point, CSHL does not have a high containment facility like Stony Brook University where it can handle highly infectious agents.

“We may have to have one here,” Stillman said. “The reality is there are tons of infectious diseases” and the lab might need to repurpose its scientific skills towards coming up with answers to difficult questions.

Even without such a Biosafety Level 3 designation, CSHL researchers have tackled ways to understand and conquer COVID-19. Associate Professor Mikala Egeblad has been exploring whether neutrophil extracellular traps, which are ways bodies fight off bacterial infections, are playing a role in blood clotting and severe respiratory distress.

These NETS may be “promoting severe symptoms in COVID,” Stillman said. Egeblad is working on a case study with several other collaborators who have focused on these traps. Egeblad is also studying the effectiveness of NETS as a biomarker for the most severe patients, Stillman said.

CSHL is also investigating a small molecule compound to see if it inhibits viral infection. Researchers including Assistant Professor Tobias Janowitz are about to participate in a combined Northwell Health-CSHL double blind study to determine the effectiveness of famotidine, which is the active ingredient in the ulcer-treating medication Pepcid.

The coronavirus treatment, which will include patients who don’t require hospitalization, would require a higher dose than for heartburn.

As a part of this study, the scientists will use a patient tracking system that has been used for cancer to determine the effectiveness of the treatment through patient reporting, without requiring laboratory tests.

Stillman is pleased with how CSHL has “repurposed ourselves quickly, as have many institutions around the world.” He highlighted the constructive interactions among scientists.

The public health crisis has “generated a different kind of behavior in science, where there’s a lot of interaction and cooperation,” Stillman said. The preprint journal BioRxiv, which CSHL operates, has had nearly 5,000 papers about COVID-19 since January. The preprints have “not only helped disseminate information rapidly [to the scientific community], but they are also “being used to determine policy by government leaders.”

Stillman urged scientists to apply the same analytical technique in reading preprinted research that they do with peer-reviewed studies, some of which have required corrections.

As for the government’s response, Stillman believes a retrospective analysis will provide opportunities to learn from mistakes. “I don’t think the [Centers for Disease Control and Prevention] has done a very good job,” he said. He suggested that the well-documented problems with the roll out of testing as community transmission was increasing, was a “disaster.”

The CSHL CEO also said the balkanized medical system, in which every state has a different system and even some local communities have their own processes, creates inefficiencies in responding to a fluid and dangerous public health crisis.

Coordinating those efforts “could have been done very, very rapidly to develop a modern, clear [polymerase chain reaction] test of this virus and yet states and federal agencies had regulations about how these tests can be approved and controlled and regulated that are far too bureaucratic and did not set a national standard quickly,” he said.

He hopes agencies like the CDC, FDA and the Biomedical Advanced Research and Development Authority have better coordination. The country needs a national response, like it had after the Homeland Security effort following 9/11.

Optimistically, Stillman expects a therapeutic antibody will be available by the end of the summer to treat COVID-19. The treatment, which will use monoclonal antibodies, will likely be injectable and will be able to prevent infection for a month or two. These treatments could also help limit the severity of symptoms for people who have been infected.

Regeneron has taken the same approach with Ebola effectively. Stillman doesn’t think such treatments can be used with everybody in the world, which increases the need to develop a vaccine. Creating a safe vaccine, which could be available as early as next year, is a “massive, under-recognized undertaking.”

Between now and next year, a second wave of the virus is certainly possible and may be likely, given that other coronaviruses have been seasonal. 

“This happened with the influenza pandemic a century ago, so we have to be careful about this,” Stillman said. He believes that the medical community has learned how to treat severe patients, which should help mitigate the effects of a second wave in the United States. 

That may not be the case in developing countries, which is a “concern,” he said.

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Mikala Egeblad with a blown-up image of a neutrophil extracellular trap, or NET. Photo from CSHL

By Daniel Dunaief

Mikala Egeblad couldn’t shake the feeling that the work she was doing with cancer might somehow have a link to coronavirus.

Egeblad, who is an Associate Professor and cancer biologist at Cold Spring Harbor Laboratory, recently saw ways to apply her expertise to the fight against the global pandemic.

She studies something called neutrophil extracellular traps, which are spider webs that develop when a part of the immune system triggered by neutrophil is trying to fight off a bacteria. When these NETs, as they are known, are abundant enough in the blood stream, they may contribute to the spread of cancers to other organs and may also cause blood clots, which are also a symptom of more severe versions of COVID-19, the disease caused by the coronavirus, which has now infected over two million people worldwide.

“I always felt an urgency about cancer, but this has an urgency on steroids,” Egeblad said.

Cold Spring Harbor Laboratory reached out to numerous other scientists who specialize in the study of NETs, sometimes picking up on the tweets of colleagues who wondered in the social networking world whether NETs could contribute or exacerbate the progression of Covid19.

Egeblad started by reaching out to two scientists who tweeted, “Nothing about NETs and Covid-19?” She then started reaching out to other researchers.

“A lot of us had come to this conclusion independently,” she said. “Being able to talk together validated that this was something worth studying as a group.”

Indeed, the group, which Egeblad is leading and includes scientists at the Feinstein Institutes for Medical Research and the Research Institute of the McGill University Health Centre, published a paper last week in the Journal of Experimental Medicine, in which they proposed a potential role for NETs.

“We are putting this out so the field doesn’t overlook NETs,” said Egeblad, who appreciated the support from Andrew Whiteley, who is the Vice President of Business Development and Technology Transfer at CSHL.

With a range of responses to the coronavirus infection, from people who have it but are asymptomatic all the way to those who are battling for their survival in the intensive care units of hospitals around the world, the biologist said the disease may involve vastly different levels of NETs. “The hypothesis is that in mild or asymptomatic cases, the NETs probably play little if any role,” she said.

In more severe cases, Egeblad and her colleagues would like to determine if NETs contribute or exacerbate the condition. If they do, the NETs could become a diagnostic tool or a target for therapies.

At this point, the researchers in this field have ways of measuring the NETs, but haven’t been able to do so through clinical grade assays. “That has to be developed,” Egeblad explained. “As a group, we are looking into whether the NETs could come up before or after symptoms and whether the symptoms would track” with their presence, she added.

To conduct the lab work at Cold Spring Harbor, Egeblad said her team is preparing to develop special procedures to handle blood samples that contain the virus. 

As the lead investigator on this project, Egeblad said she is organizing weekly conference calls and writing up the summaries of those discussions. She and the first author on the paper Betsy J. Barnes, who is a Professor at the Feinstein Institute, wrote much of the text for the paper. Some specific paragraphs were written by experts in those areas.

At this point, doctors are conducting clinical trials with drugs that would also likely limit NET formation. In the specific sub field of working with this immune-system related challenge, researchers haven’t found a drug that specifically targets these NETs. 

If the study of patient samples indicates that NETs play an important role in the progression of the disease, particularly among the most severe cases, the scientists will look for drugs that have been tried in humans and are already approved for other diseases. This would create the shortest path for clinical use.

Suppressing NETs might require careful management of potential bacterial infections. Egeblad suggested any bacterial invaders might be manageable with other antibiotics.

NETs forming in airways may make it easier to get bacterial infections because the bacteria likes to grow on the DNA.

Thus far, laboratory research studies on NETs in COVID-19 patients have involved taking samples from routine care that have been discarded from their daily routine analysis. While those are not as reliable as samples taken specifically for an analysis of the presence of these specific markers, researchers don’t want to burden a hospital system already stretched thin with a deluge of sick patients to provide samples for a hypothetical pathway.

Egeblad and her colleagues anticipate the NETs will likely be more prevalent among the sicker patients. As more information comes in, the researchers also hope to link comorbidities, or other medical conditions, to the severity of COVID-19, which may implicate specific mechanisms in the progression of the disease.

“There are so many different efforts” to understand what might cause the progression of the disease, Egeblad said. “Everybody’s attention is laser focused.” A measure that is easy to study, such as this hypothesis, could have an impact and “it wouldn’t take long to find out,” she added. Indeed, she expects the results of this analysis should be available within a matter of weeks.

Egeblad believes the NETs may drive mucus production in the lungs, which could make it harder to ventilate in severe cases. They also may activate platelets, which are part of the clotting process. If they did play such a role, they could contribute to the blood clotting some patients with coronavirus experience.

Egeblad recognizes that NETs, which she has been studying in the context of cancer, may not be involved in COVID-19, which researchers should know soon. “We need to know whether this is important.”

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A view of Cold Spring Harbor Laboratory. File photo
Cold Spring Harbor Laboratory’s DNA Learning Center will be closed effective Monday, March 15, according to a statement from CSHL, until further notice.The DNALC will be closed to the public and will not hold in-person programs at any location or through school visits. The decision was made in response to the current COVID-19 pandemic.

According to a statement from the facility, there is no evidence of staff or recent visitors with the virus.

DNALC will monitor the situation and resume operations as soon as possible, and it will maintain future bookings as placeholders until it reopens and reschedule as needed.

For more information, call 516-367-5170 or [email protected].

Last week, CSHL canceled all public events until April.

 

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Stock photo

*Update* This post has been amended to reflect new cases of coronavirus in Suffolk County as well as new info from town and county sources.

In the same week the World Health Organization called the coronavirus outbreak a pandemic, Suffolk County recorded its first six positive tests for COVID-19.

The first four people to have the virus contracted it through community transmission, which means that none of them traveled to countries where infections are more prevalent. The patients include a Brookhaven Town man in his 20s who is in isolation at Stony Brook University Hospital, a Southold resident who is in her 20s and is under home isolation, a man in his 80s who is in isolation at St. Catherine’s Hospital and a man in his 40s who is in isolation Stony Brook Southampton Hospital. 

At the same time, eight people were under mandatory quarantine while the New York State Department of Health is monitoring 72 people under precautionary quarantine because of their travel abroad, according to officials from the Suffolk County Health Department.

Dr. Gregson Pigott, commissioner of the county Department of Health Services, said the patient is “getting better” and expected that he will “be fine.” 

Pigott said several area facilities have developed the ability to test for COVID-19, including LabCorp and Northwell Health Labs, which received state and federal approval to start manual testing for the virus. Northwell is seeking U.S. Food and Drug Administration approval to use semi-automated testing within the week, which could boost the number of tests to the hundreds per day and into the thousands in the near future, the health lab said.

Pigott said Suffolk County was “on top of” the virus “for now” but that the circumstances could change, which is why several facilities have taken steps to protect various populations.

Stony Brook University told students this week that it would transition to all online classes starting on March 23, according to a letter sent out to students. The online version of the classes will continue through the end of the spring semester. Stony Brook is one of several colleges throughout the country that is taking steps to protect students through online versions of their classes. Princeton University, Stanford University, Harvard College and the University of Washington, to name a few, are also teaching classes online. Hofstra University canceled classes this week as well.

On March 10, Stony Brook’s Staller Center canceled all events for March “out of an abundance of caution” due to the coronavirus, according to a release.

Meanwhile, the New York State Education Department and the State Department of Health issued updated guidance to school and community health officials, which includes requiring schools to close for 24 hours if a student or staff member attended school prior to being confirmed as a positive COVID-19 patient. Additionally, during that period the school is expected to disinfect the building or buildings where the person had contact prior to testing positive. The departments also urged schools to work with community feeding organizations to plan for distribution of food to students who rely on the two meals served at schools each day.

The local health department will notify schools if and when they are required to close because of the virus and when they can reopen. Schools are not expected to decide about closing or canceling events on their own.

Cold Spring Harbor Laboratory has canceled all public events, including lectures and on-site visits, through April 30.

Brookhaven National Laboratory, responding to guidance from the U.S. Department of Energy, has suspended all international business travel, with an exception for mission-essential international travel. Staff returning from China, Iran, South Korea and Italy are required to self-quarantine for 14 days. Staff will also have to self-quarantine if a household member traveled to those countries. All in-person visits of people from those countries are postponed.

Meanwhile, county Sheriff Errol Toulon Jr. (D) suspended all contact visits with prisoners. Noncontact visits can still be scheduled in advance, while visiting hours will be 7:30 a.m. to 8:30 p.m. and will be limited to 30-minute sessions.

To protect the most vulnerable population, the U.S. State Department also made recommendations to senior facilities. Following those guidelines, Affinity Skilled Living in Oakdale started screening staff and visitors earlier this week, which includes taking their temperature. The facility also has restricted visiting hours.

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A view of Cold Spring Harbor Laboratory. File photo

With six cases of coronavirus Covid-19 in New York state confirmed as at March 4, state, local institutions are preparing for the potential spread of the virus.

New York lawmakers earlier this week passed a $40 million spending bill. The funds will allow the Department of Health to hire staff, purchase equipment and gather additional resources to address a virus for which a travel ban no longer seems sufficient to ensure containment.

A 50-year old Westchester man tested positive for the virus, even though he didn’t travel to areas of contamination, which include China, South Korea and Italy, and didn’t have known contact with anyone who has traveled to those areas. Through the so-called community spread of the virus, which has a mortality rate of more than 3 percent, can infect a wider range of people.

Northwell Health Labs said earlier this week it expects to begin testing for Covid-19 within a week. The health facility, which announced the future testing at a news conference March 2 with U.S. Sen. Chuck Schumer (D-NY), said manual testing could involve 75 to 100 tests each day. After it automates the tests, the facility could process hundreds and even thousands of tests on a daily basis. Mather Hospital in Port Jefferson is part of Northwell Health group.

Meanwhile, Brookhaven National Laboratory, Cold Spring Harbor Laboratory and Stony Brook University have made recommendations to staff who might travel to areas of infection.

BNL is following the recommendations of the Centers for Disease Control and the State Department regarding health notices and travel advisories. The U.S. State Department has a do-not-travel restriction on trips to China and Iran, along with specific areas of Italy and South Korea, while it also recommends reconsidering travel to Italy, South Korea and Mongolia.

Also, BNL is asking visiting scientists if they traveled to China or live with someone who visited China within 14 days. If the answer to either question is “yes,” these individuals have to complete a 14-day period away from China without symptoms before returning to the lab.

BNL canceled the International Forum on Detectors for Photon Science conference, which was scheduled for March 29 through April 1 at Danfords Hotel in Port Jefferson. The conference was expected to have 40 participants.

CSHL has canceled or postponed all upcoming conferences and courses bringing participants to campus through April 5th. The laboratory will reevaluate future offerings on a rolling basis.

Also, CSHL is cleaning common areas including bathrooms, counters and dining areas more frequently, is providing more hand sanitation stations, is enhancing the readiness of its Center for Health & Wellness and is providing secure transfer protocols for at-risk people with potential symptoms of the virus.

SBU discouraged school-related and personal travel to China, Italy, Iran and South Korea. The school also created a mandatory preapproval requirement for all publicly funded university-sponsored travel plans to China, Italy, Iran and South Korea. SBU has not canceled the Florence University of the Arts program, since the university is continuing classes as usual and the Tuscany region doesn’t have any reported cases of the virus.

On a national level, the Federal Reserve, in a move similar to decisions from other central banks, cut interest rates by half a percentage point, the biggest cut since the financial crisis of 2008. The cut was designed to stave off an economic slowdown caused by business disruptions from the coronavirus.

“The coronavirus poses evolving risks to economic activity,” the Federal Reserve said in a statement.

Updated March 5 to reflect most current CSHL procedures regarding conferences and courses.

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Lingbo Zhang Photo from CSHL

By Daniel Dunaief

In the span of a few months, Lingbo Zhang, a Cold Spring Harbor Laboratory fellow, has made discoveries involving two deadly blood cancers.

In September, Zhang, collaborating with researchers from Memorial Sloan Kettering Cancer Center and the National Institute of Diabetes and Digestive and Kidney Diseases, found a drug target that might eventually lead to a new treatment for myelodysplastic syndrome, which is a common form of blood cancer. The scientists published their work in the journal Science Translational Medicine.

In January, Zhang published work that analyzed the genes that are active in acute myeloid leukemia, which has a five-year survival rate of only 33 percent. 

By studying 230 genes, Zhang found that this form of blood cancer is addicted to higher concentrations of vitamin B6, creating a potential target for future therapy. The CSHL scientist published this work in the journal Cancer Cell.

“We feel humbled that we found a target” for a future AML therapy, Zhang said of his latest discovery. “My lab partners and I think one day we can potentially translate our knowledge into a real therapy. The translational part gives us the energy and encouragement to work hard.”

Indeed, Zhang explained that his work broadly focuses on blood cancer, in which he looks for questions of medical importance. With MDS, he started with the view that many patients with this disease do not respond to the typical treatment using a hormone called erythropoietin, or EPO.

Lingbo Zhang

People with MDS typically have too few red blood cells, which are made in bone marrow. The hormone EPO converts progenitor immature versions of red blood cells into the ones that function in the body. A small percentage of MDS patients, however, respond to EPO. This occurs because people with this disease have a smaller pool of progenitor cells.

Zhang and his colleagues went upstream of those progenitor cells, searching for defective processes earlier in the pathway. They found that a protein receptor, CHRM4, decreases the production of cells that might become red blood cells. 

By inhibiting that receptor, they hoped to restore the red blood cell making process. In mice that have the same blood features as human MDS, this approach worked, restoring the machinery that leads to the production of red blood cells.

With both the MDS and the leukemia studies, these discoveries might lead to a future treatment, but are not necessarily the final step between understanding molecular signals and developing treatments. These findings are transitioning from basic discoveries into the preclinical development of novel therapies, Zhang said.

For MDS, the treatment may be effective with the inhibitor itself, while for AML, it will potentially be effective as part of a therapy in combination with other treatments.

In his work on leukemia, Zhang said the research went through several phases, each of which took several months. For starters, he screened all the potential target genes. Once he performed the initial work, he conducted a validation study, exploring each gene, one by one. Finally, he worked to validate the study.

After all that work, he discovered the role that the gene that makes PDXK, the enzyme that helps cells use vitamin B6, plays in contributing to cancer. Normal, healthy cells use vitamin B6 during metabolism to produce energy and grow. As with most cancers, leukemia involves more cell division than in a healthy cell, which means that the PDXK enzyme is more active.

Scott Lowe, a collaborator on the research and former CSHL fellow who is now the chair of Cancer Biology and Genetics at Memorial Sloan Kettering, expressed surprised at the finding. “While the action of certain vitamins has previously been linked to cancer, the specific links between vitamin B6 identified here were unexpected,” he said in a press release.

A postdoctoral researcher in Zhang’s lab who has been working on the project for two years, Bo Li plans to continue this research and hopes to find a more mechanistic understanding of the discovery.

While this vitamin contributes to cancer, people with leukemia shouldn’t reduce their consumption of B6, which is necessary in healthy cells. If normal and cancer cells both need this vitamin, how could this be a target for drugs?

The difference, Zhang explained, is in the concentration of the enzyme and, as a result, the B6.

PDXK is higher in leukemia. Reducing its activity by inhibiting this activity could affect the disease.

Working with a collaborator at Memorial Sloan Kettering, Zhang is hoping to develop a better chemical compound with the right property to target the activity of this gene and enzyme.

To conduct research into different diseases and pathways, Zhang works with a group of “very talented and hard working people,” in his lab, which includes a few postdoctoral researchers, a doctoral student, a few undergraduates and a technician, bringing his lab’s staff to eight people. “We also have very good collaborators at other institutes and we are able to manage several projects in parallel,” he said.

Zhang said he likes basic and translational science. The basic science brings “beautiful new theories that identify a detail nature created.” He also feels driven to “translate some of these basic discoveries into a potential treatment,” he said. He is working with a foundation and the hospital and receives patient information from them, which encourages him to work hard to seek ways to “benefit them.”

Down the road, he hopes to understand the hierarchical process that leads from stem cells to mature blood cells. By identifying a majority of the players or the regulators, he may be able to understand the different processes involved in the course of numerous diseases.

As for his current work, Zhang is pleased with the potential translational benefit of both discoveries. “I feel very happy that we can identify a target for leukemia and MDS,” he said.

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Analyzing Ötzi

Fifth-grade students from Cold Spring Harbor Central School District’s Lloyd Harbor Elementary School took part in a field trip to Cold Spring Laboratory’s DNA Learning Center’s Human Inheritance exhibition featuring Ötzi the Iceman on Jan. 6.

Students studied the 3-D replica of the 5,000-year-old mummy and learned how, through analysis of Ötzi’s stomach and intestines, many pollen types were revealed and studied to help scientists learn exactly when Ötzi died. 

Under the guidance of DNA Learning Center educator Megan Capobianco, the students studied pollen grains under the microscope and then went on a scavenger hunt, which included skulls dating back 6 million years, bacterial illnesses, eye color, blood type and more. The fifth-graders learned that not only pollen was found in Ötzi’s digestive system but also wild goat, red deer, plants and wheat. 

The DNA Learning Center is located at 334 Main St. in Cold Spring Harbor. Upcoming Ötzi the Iceman museum tours for the public include Feb. 8 at 9 a.m. and March 7 at 12:30 p.m. For more information, call 516-367-5170 visit www.dnalc.cshl.edu.

Photos courtesy of Karen Spehler/ CSHSD

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