Tags Posts tagged with "Cold Spring Harbor Laboratory"

Cold Spring Harbor Laboratory

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.

 

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.

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.