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Cold Spring Harbor Laboratory

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.”

Cold Spring Harbor Laboratory has halted all public events until April due to the Coronavirus. 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.

 

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.

Cold Spring Harbor Laboratory has halted all public events until April due to the Coronavirus. 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.

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.

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

Dave Jackson. Photo from CSHL

By Daniel Dunaief

Just as humans have competing impulses — should we eat or exercise, should we wait outside in the rain to meet a potential date or seek shelter, should we invest in a Spanish tutor or a lacrosse coach — so, too, do plants, albeit not through the same deliberate abstract process.

Working with corn, Dave Jackson, a professor at Cold Spring Harbor Laboratory, has discovered that the gene Gß, (pronounced Gee-Beta,) balances between the competing need to grow and to defend itself against myriad potential threats.

By looking at variations in the gene, Jackson and his postdoctoral fellows, including Qingyu Wu and Fang Xu, have found that some changes in Gß can lead to corn ears with more kernels. The results of this work, which were published in the Proceedings of the National Academy of Sciences last month, suggest that altering this gene may eventually increase the productivity of agricultural crops.

Indeed, the study of this gene included an analysis of why some mutations are lethal. An overactive Gß gene turns the corn brown and kills it. This occurs because the gene cranks up the immune system, causing the plant to attack itself.

Other scientists have found mutations in this gene in plants including arabodopsis and rice.

“We are the first to figure out why the mutations are lethal in corn,” Jackson said. “That’s also true in rice. Rice mutations were made over a decade ago and they also caused the plants to die. Nobody knew why. The main puzzle was solved.”

Dialing back this immune response, however, can encourage the plant to dedicate more resources to growth, although Jackson cautions that the research hasn’t reached the point where scientists or farmers could fine tune the balance between growth and defense.

“We are not there yet,” he said. “That’s what would be possible, based on this knowledge.”

Even in the safer environment of an agricultural field, however, plants can’t abandon all efforts at defense.

“Plants need some defense, but probably much less than if they were growing in the wild,” he said.

By altering the balance toward growth, Jackson is looking at mutations that make more stem cells, which can produce flowers and, eventually kernels. The next steps in this research will not likely include scientists in Jackson’s lab. Qingyu Wu plans to move on to a research position in China. 

Penelope Lindsay. Photo by Patricia Waldron

A prolific plant scientist and mentor, Jackson has seen several of his lab members leave CSHL to pursue other opportunities. Recently, he has added three new postdoctoral researchers to his team: Thu Tran, Jae Hyung Lee and Penelope Lindsay.

Jackson plans to use single-cell sequencing in his future research. Using this technique, scientists can find regulatory relationships between genes and monitor cell lineages in development. Jackson described this approach as an “amazing new technology” that’s only been around for a few years. He hopes to use this technique to find new leads into genes that control growth.

Lindsay, who is joining the lab this month, would like to build on her experience as a plant biologist by adding computational expertise. A graduate of the Boyce Thompson Institute in upstate Ithaca, where she was working on the symbiotic relationship between some plants and a specific type of fungi in the soil, Lindsay would also like to work on single-cell sequencing. She plans to continue to study “how specific genotypes produce a phenotype” or how its genes affect what it becomes.

Jackson’s lab’s focus on the undifferentiated cells of the meristem appealed to Lindsay.

Lindsay first met Jackson a few years ago, when he was giving a talk at Cornell University. It was there, fittingly enough, that she had learned about the work that led to the current paper in the Proceedings of the National Academy of Sciences about growth versus defense.

“I was really impressed with the techniques and with the connection to basic research,” Lindsay said. She was excited to learn how Jackson and his students took biochemical approaches to understand how this signaling pathway affected development.

Cold Spring Harbor Laboratory also intrigued Lindsay, who was interested to join a facility that encouraged collaborations among labs.

Born in New York City, Lindsay spent some of her time in upstate New York before moving to Florida, where she also attended college.

Surrounded by family members who have found outlets for their creativity through art — her mother, Michelle Cartaya, is an artist who takes nature photos and her father, Ned Lindsay, remodels homes — she initially attended New College of Florida in Sarasota expecting to pursue a degree in English. Once in college, however, she found excellent scientific mentors, who encouraged her to pursue research.

As a graduate student, Lindsay was greatly intrigued by the signaling pathway between plants and the symbiotic relationship with arbuscular mycorrhizal fungi. During her graduate work, she studied a mutated version of a plant that lacked a signaling protein that encourages this collaboration. When she added considerable amount of the protein to the plant, she expected to restore the symbiosis, but she found the exact opposite.

“The amount of the protein is critical,” she said. “If you have too much, that’s a bad thing. If you don’t have enough, it’s also bad. It’s like Goldilocks.”

A new resident of Huntington, Lindsay, who was a disc jockey for a community radio station in Ithaca and makes electronic music using synthesizers and computers, is looking forward to starting her work at Cold Spring Harbor Laboratory and to living near New York City.

Lindsay continues to find plants fascinating because they “get everything they need” while living in one place their entire lives. “They have so many sophisticated biochemical pathways to protect themselves,” she said.

Saket Navlakha

By Daniel Dunaief

Plants have to solve challenges in their environment – without a brain or the kind of mobility mammals rely on to survive – through strategies and computations that keep them alive and allow them to reproduce.

Intrigued by plants and by the neurobiology that affect decisions or behavior in a range of other organisms, Associate Professor Saket Navlakha recently joined Cold Spring Harbor Laboratory to study the processes a range of organisms use.

“Biological systems have to solve problems to survive,” said Navlakha. “The hope is that by studying these algorithms, we can inspire new methods for computer science and engineering and, at the same time, come up with new ways to predict and model behaviors of these systems.”

Navlakha, who has a doctorate in computer science from the University of Maryland College Park and conducted postdoctoral research at Carnegie Mellon University’s Machine Learning Department, focuses on the “algorithms of nature,” in which organisms evolved ways to solve problems that enhance the likelihood of their survival.

In his first three months at CSHL, Navlakha plans to do an interview tour, speaking with researchers who study cancer, molecular biology, neurology and plants.

While his primary areas of focus have been on plants and neurobiology, he appreciates that the internationally recognized research facility presents “new opportunities” for him and a lab in which he intends to hire four to six scientists over the next two years.

Adam Siepel, the chair of the Simons Center for Quantitative Biology and professor at the Watson School of Biological Sciences at Cold Spring Harbor Laboratory, led the recruitment of Navlakha.

In an email, Siepel wrote that Navlakha “immediately struck us as an ideal candidate for the center” in part because he is a “free thinker with an eye for interesting and important problems in biology.”

Navlakha believes processes and strategies that foster survival spring from a set of principles that helps them thrive and adapt. In 2018, when he was at the Salk Center for Integrative Biology, he wrote a piece for Wired magazine about species extinction. “By not preserving [species that become extinct], we are losing out on interesting ideas that evolution gave them to survive,” he said.

Even amid these losses, however, Navlakha recognizes the lessons computer scientists and engineers like him can learn. Through losses and failures, humans can understand the limitations of algorithms that only allowed a species to survive up to a point, as conditions pushed its algorithms past a tipping point.

At its core, Navlakha’s approach to these algorithms includes the idea that biological systems perform computations. He originally studied brains because they are “such an elegant computer, doing all kinds of things that modern, human-made computers can’t do,” he said.

When he was at the Salk Institute, he spoke with colleagues in plant biology who told him about research that examined how plants modify their shape amid a changing environment, which is what triggered his interest in plants.

One of the themes of his work involves understanding trade-offs. Doing well in one task typically means doing worse in another. He likened this analysis to investing in stocks. An investor can put considerable funds into one stock, like Apple, or diversify a portfolio, investing less money per stock in a variety of companies from different sectors.

“We’ve been studying how plants hedge” their bets, he said. The hedge in this description bears no relation to a collection of plants at the edge of a property.

A plant can create one huge seed that might survive a drought or other environmental threat, or it can diversify the types of seeds. “We’re really interested in understanding these trade-offs, how they hedge, and what kind of strategies” they employ, he said.

Ziv Bar-Joseph, a professor of computer science at Carnegie Mellon University who has known Navlakha for over eight years, suggested Navlakha has “deep insights.” 

In an email, Bar-Joseph described Navlakha’s biggest achievement as his work that shows how the brain uses a computational method to store and retrieve smells. 

“This work both solved an important mystery about how the brain functions and informed us on novel usages of an important computational method, thus contributing to both areas,” Bar-Joseph explained.

Navlakha doesn’t have a typical laboratory filled with beakers, pipettes or plants growing under various conditions. He relies on wet labs to provide data that he then interprets and analyzes as a part of the Simons Center for Quantitative Biology. While his training is in computer science, he has shown a talent for experimental research as well. 

Bar-Joseph recalled how Navlakha performed experiments and analysis. In a short time, Navlakha “was able to master very involved techniques and obtained very good results.” 

Navlakha explained that the work he does colors the way he sees the world. “People walk by plants without paying attention to the incredible computations that they’re doing to keep us on this planet,” he said. “Computation is the basis of life.”

A resident of Great Neck, Navlakha recently married Sejal Morjaria, an infectious disease physician at Sloan Kettering, who works with patients who have cancer. The couple met through an online dating app when he was in San Diego and she lived in New York. They chatted for a while without any expectation of seeing each other, until he traveled to Washington, D.C                                 for a conference.

Navlakha enjoys playing numerous sports, including tennis and basketball. He also played hockey. He and Morjaria participate in yoga classes together.

Navlakha, who grew up in Miami, Florida, said he had to readjust to life on Long Island after living in Southern California for several years. “San Diego makes you weak,” he joked.

In his work, Navlakha hopes to bring together two fields in a different way.

Given the importance of computations, Navlakha appreciates a corollary to the concept proposed by Rene Descartes’ “I think, therefore I am.” For Navlakha, “I compute, therefore I am” describes processes he studies among animals and plants.

Nicholas Gladman with a harvest of sorghum at Cornell University’s Long Island Horticultural Research Lab in Riverhead. Photo by Sendi Mejia

By Daniel Dunaief

When people buy a bag of potato chips, they often find that half of the bag is filled with air. The same is true of a sorghum plant, which produces livestock feed and is converted into ethanol, part of many gases that power cars.

Nicholas Gladman

In a typical sorghum plant, half of the flowers become grain, while the other half remain infertile. As the world grapples with food shortages and scientists seek ways to increase the yield of a wide array of plants, researchers at Cold Spring Harbor Laboratory wondered whether they could increase that yield.

Building on previous work done in the lab of Doreen Ware, an adjunct professor at CSHL, postdoctoral fellow Nicholas Gladman characterized a mutation for a single gene that lowered the level of a hormone. The effect of the lower hormone, or jasmonic acid, at a specific time and place within plant development doubled the fertility of the sorghum plant.

“When we don’t have a functional version of this enzyme, it releases this form of development that wouldn’t normally occur,” Gladman said. “You get increased fertility in flowers.”

The gene they studied is called MSD2. The researchers published their work in International Journal of Molecular Sciences. Another gene, MSD1, which Ware’s lab characterized in 2018, is a likely regulator for MSD2. Other genes may also serve as regulators of MSD2, Gladman said. Disruptions in either gene leads to altered flower development and seed production.

Gladman’s postdoctoral research adviser Zhanguo Xin collaborated on the work. Xin, who is a research molecular biologist at the United States Department of Agriculture’s Agricultural Research Service, explained that Gladman characterized the mutants, identified the interaction between MSD1 and MSD2 and identified the regulatory sequences of MSD1.

This research could extend to other cereal crops, which have the same conserved sets of genes that affect their growth and fertility.

A concern in altering any gene resides in the overall effect on the health of the plant. Creating a super plant that falls over and dies in a slight wind, can’t fend off common infections, or requires a perfect blend of soil would likely offset the benefit of the increased fertility. Plant geneticists would like to ensure any mutation doesn’t make the plant less viable in the long run.

“Sometimes there can be a trade off between an agriculturally beneficial genetic change by introducing other detrimental effects,” Gladman explained in an email. “Optimally, plant geneticists will try to ensure the side effects of any mutation are insignificant to farmers; sometimes, this is more difficult and the downsides may not always present themselves at the early stages of lab investigation.”

This particular gene is narrowly and spatially expressed within the plant, Gladman said, and the researchers haven’t been able to identify or quantify the effect of this gene on anything else other than flowers and floral architecture.

The gene and the hormone would be a concern if it were expressed more broadly and at high levels throughout other plant tissues, but that doesn’t seem to be the case, he said.

The researchers have looked at other tissues, such as the leaf and stem, and have found that MSD2 is expressed in low levels in these other areas. Plants that have the MSD2 mutation do not demonstrate any noticeable differences in growth compared to nonmutants in the field or in greenhouse conditions. If this mutated gene had an agricultural benefit, farmers would likely crossbreed a plant that had this gene with an elite sorghum hybrid line

Ideally, the benefits of the increased fertility would combine with benefits of all the genetic components of the hybrid lines as well. The way the researchers involved in this study produced this more fertile version of sorghum is an “acceptable type of breeding for organic or conventional farming,” Gladman said.

While the plant increases the grain number per seed head, it doesn’t necessarily produce greater overall yield in part because the seeds are smaller. Researchers haven’t been able to confirm that yet in a field condition, although they hope that’s the case.

Gladman was grateful for the opportunity to work in Ware’s lab and to collaborate with Xin. The effects of disrupting similar genes in maize and Arabidopsis, which is a plant in the mustard family that scientists often use in genetic studies, influences flower fertility.

He said researchers in Ware’s lab can perform additional developmental analysis. The researchers in Ware’s lab may seek additional collaborators for other analyses down the road as well.

“How this particular pathway is triggered and cross-communicates with other developmental pathways is very complex, but influences so much about traits that control grain production and yield that it is essential for further investigations,” he explained.

Gladman arrived at Cold Spring Harbor Laboratory in 2017. Prior to conducting research on Long Island, he finished his doctorate at the University of Wisconsin at Madison, where he worked on Arabidopsis. He decided he wanted to get more involved with crop species and explored research opportunities at United States Department of Agriculture labs. He was working with Xin in Lubbock, Texas, before transitioning to Cold Spring Harbor Laboratory.

Gladman has been delighted by the “wonderful place to learn,” where he is surrounded by “people who are always willing to talk and engage and collaborate.”

A resident of Greenlawn, Gladman enjoys hiking along the Hudson and in the Adirondacks. He credits a high school biology class he took in Grandview Heights High School in Columbus, Ohio, with instilling in him and his three brothers an appreciation and love of science. He particularly enjoyed a unit on the “genetics of disease” that inspired him to pursue a career in the sciences.

As for his work, Gladman is excited to be a part of research that may, one day, increase the productivity of crop species. He said thoughts about food shortages are “a constant concern and driver of our research.”

 

Interns Nylette Lopez (rear) and Stephanie Taboada characterize catalysts as they attempt to convert carbon dioxide and methane into synthesis gas this past summer at Brookhaven National Laboratory. Photo from BNL.

By Daniel Dunaief

This article is part two in a two-part series.

Local medical and research institutions are aware of the challenges women face in science and are taking steps to ensure that women receive equal opportunities for success in science, technology, engineering and mathematics (or STEM). Times Beacon Record News Media reached out to members of each institution and received an overview of some initiatives.

Brookhaven National Laboratory 

The Department of Energy-funded research facility has created a number of opportunities for women, including Brookhaven Women in Science. This effort has been active for over four decades and its mission, according to Peter Genzer, a BNL spokesman, is to support the development of models, policies and practices that enhance the quality of life for BNL employees and emphasize the recruitment, hiring, promotion and retention of women.

BWIS offers annual awards, outreach events and various networking opportunities in the lab and community, while the lab’s Talent Management Group partners with BWIS to bring classes and speakers to discuss issues specific to women.

In October, the group hosted Kimberly Jackson, a vice chair and associate professor of chemistry and biochemistry at Spelman College, who gave a talk titled “Realigning the Crooked Room in STEM.”

The Leona Woods Distinguished Postdoctoral Lectureship Award at BNL, meanwhile, celebrates the scientific accomplishments of female physicists, physicists from under-represented minority groups and LGBTQ physicists and to promote diversity and inclusion. BNL awarded the lectureship this year to Kirsty Duffy, a fellow at Fermi National Accelerator Laboratory.

For the past five years, BNL has also partnered with a local chapter of Girls Inc., which helps to “encourage young women towards careers” in STEM, Genzer explained in an email.

BNL has also collaborated with the Girl Scouts of Suffolk County to organize a new patch program that encourages Girl Scouts to work in scientific fields. As of September, county Girl Scouts can earn three new Brookhaven Lab patches, and the lab hopes to extend the program nationwide across the Department of Energy complex.

BNL also provides six weeks of paid time off at 100 percent of base pay for a primary caregiver after birth or adoption and one week of full pay for a secondary caregiver. BNL is exploring plans to enhance support for primary and secondary caregivers, Genzer said.

Cold Spring Harbor Laboratory

Cold Spring Harbor Laboratory has taken several recent steps as part of an ongoing effort to encourage gender diversity.

In October, a group of four CSHL administrators traveled to the University of Wisconsin in Madison to discuss mentoring. The goal was to train them on how to design and deliver mentoring training regularly to the faculty, postdocs and graduate students on campus, said Charla Lambert, the diversity, equity and inclusion officer for research at CSHL. The first version of the training will occur next spring. The ultimate goal is to ensure the research environment at CSHL emphasizes good mentoring practices and is more inclusive for all mentees.

CSHL has also hosted a three-day workshop in leadership practices for postdoctoral researchers and junior faculty since 2011. The workshop, which is run through the Meetings & Courses Program, trains about 25 postdoctoral researchers and junior faculty each year and has about one per year from CSHL, addresses how to hire and motivate people, while providing constructive feedback.

Lambert said family-friendly policies were already a part of CSHL policies, which include a child care facility. Members of the faculty receive extra funding when they travel to conferences to provide additional child care.

Lambert, who is a program manager for extramural Meetings & Courses overseeing diversity initiatives, has worked to get the demographic data for participants centralized, analyzed and used in developing policies. She believes this kind of data centralization is an area for potential improvement in the research division, where she is working to ensure an equitable distribution of resources among CSHL scientists.

Throughout her nine-year career at CSHL, Lambert said she has worked with the meetings and courses division to make sure the 9,000 scientists who visit the facility each year include women as invited speakers. She also works to reach course applicants from a wide range of institutions, including outside of prestigious research schools.

Ultimately, Lambert is hoping to help change the culture of science among the researchers with whom she interacts from a wide range of institutions. She feels that those people who leave the STEM fields because something about the culture of science didn’t work for them represent a “huge loss” to the field and creates a “survivorship bias.”

Stony Brook University 

For Stony Brook, gender diversity is “very important,” said Latha Chandran, the vice dean for Academic and Faculty Affairs at the Stony Brook University Renaissance School of Medicine. 

Chandran said more men entered the field of medicine 14 years ago. That has completely changed, as women have outnumbered their male counterparts in medicine for the last three or four years.

Chandran cited a number of statistics to indicate changes at the medical school. For starters, women faculty constituted 38 percent of the total in 2011. This April, that number climbed to 48.1 percent. That puts Stony Brook in the top 79th percentile of medical schools in terms of female representation.

While the overall numbers are higher, women are still underrepresented in the top tiers of the medical school, as 18 percent of the department chairs are women. She hopes more women can lead departments and that they can serve as role models that others can aspire to follow.

As for harassment, Chandran said Stony Brook was above the national mean in 2011. For almost all categories, Stony Brook is now below the national mean.

In 2011, Stony Brook created We Smile, which stands for We can Eradicate Student Mistreatment in the Learning Environment. The goal of this program is to educate people about harassment and to ensure that any mistreatment is reported. Through this effort, Stony Brook medical students are aware of the policies and procedures surrounding reporting.

Stony Brook is also addressing any bias in admission procedures by prospective applicants, who receive a standardized scenario to address with an admissions officer. In 2025, admissions officers will not have any information about the qualifications of the individual and will evaluate his or her response during interviews only based on response to scenarios.

Stony Brook University has almost finalized its search for a chief diversity candidate. Chandran expects that the medical school will “continue to make progress.”