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Daniel Dunaief

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Peter Westcott, on right, in the lab with technicians Zakeria Aminzada, on left and Colin McLaughlin, center. Photo by Steven Lewis

By Daniel Dunaief

When Peter Westcott was growing up in Lewiston/Auburn, Maine, his father Johnathan Harris put the book “Human Genome” on his bed. That is where Westcott, who has a self-described “obsessive attention to detail,” first developed his interest in biology.

Westcott recently brought that attention to detail to Cold Spring Harbor Laboratory, where he is an assistant professor and Cancer Center member. He, his wife Kathleen Tai and their young children Myles and Raeya moved from Somerville, Massachusetts, where Westcott had been a postdoctoral fellow at the Koch Institute of Integrative Cancer Research at the Massachusetts Institute of Technology.

Westcott will take the passion and scientific hunger he developed and honed to the famed lab, where he plans to continue studies on colon cancer and the immune system.

“A lot of things attracted me to Cold Spring Harbor Laboratory,” said Westcott who had been to the lab during conferences, joining three Mechanisms and Models of Cancer meetings, and appreciated that the small size of the lab encourages collaboration and the sharing of ideas across disparate fields.

At this point, Westcott, who purchased a home in Dix Hills and started on campus on September 1st, has two technicians, Zakeria Aminzada and Colin McLaughlin working with him. He will be taking on a graduate rotation student from Stony Brook University soon and would also like to add a postdoctoral researcher within about six months. He plans to post ads for that position soon. 

Research directions

Westcott said his research has two major research directions.

The first, which is more translatable, involves looking at how T cells, which he described as the “major soldiers” of the immune system, become dysfunctional in cancer. These T cells balance between attacking unwanted and unwelcome cells relentlessly, disabling and destroying them, and ignoring cells that the body considers part of its own healthy system. When the T cells are too active, people develop autoimmunity. When they aren’t active enough, people can get cancer.

“Most cancers, particularly the aggressive and metastatic ones, have disabled the immune response in one way or another, and it is our focus to understand how so we can intervene and reawaken or reinvigorate it,” he explained.

During cancer development, T cells may recognize that something on a tumor is not healthy or normal, but they sometimes don’t attack. Depending on the type of genetic program within the T cells that makes them tolerant and dysfunctional, Westcott thinks he can reverse that.

A big push in the field right now is to understand what the genetic programs are that underlie different flavors of dysfunction and what cell surface receptors researchers can use as markers to define T cells that would allow them to identify them in patients to guide treatment.

Westcott is taking approaches to ablate or remove genes called nrf4a 1, 2 and 3. He is attacking these genes individually and collectively to determine what role they play in reducing the effectiveness of the body’s immune response to cancer.

“If we knock [some of these genes] out in T cells, we get a better response and tumors grow more poorly,” he said.

Westcott is exploring whether he can remove these genes in an existing T cell response to cause a regression of tumor development. He may also couple this effort with other immunotherapies, such as vaccines and agonistic anti-CD40 antibody treatment.

As a second research direction, Westcott is also looking more broadly at how tumors evolve through critical transitions. Taking an evolutionary biology perspective, he hopes to understand how the tumors start out as more benign adenoma, then become malignant adenocarcinoma and then develop into metastatic cancer. He is focusing in particular on the patterns of mutations and potential neoantigens they give rise to across the genome, while concentrating on the immune response against these neoantigens.

Each tumor cell is competing with tumor cells with other mutations, as well as with normal cells. “When they acquire new mutations that convey a selective advantage” those cells dominate and drive the growth of a tumor that can spread to the rest of the body, Westcott said.

Using a mouse model, he can study tumors with various mutations and track their T cell response.

T cells tend to be more effective in combating tumors with a high degree of mutations. These more mutated tumors are also more responsive to immunotherapy. Westcott plans to study events that select for specific clones and that might shift the prevalence, or architecture, of a tumor.

Some of the work Westcott has done has shown that it is not enough to have numerous mutations. It is also important to know what fraction of the cancer cells contain these mutations. For neoantigens that occur in only a small fraction of the total cells in the tumor, the T cell responses aren’t as effective and checkpoint blockade therapy doesn’t work.

He wants to understand how the T cell responses against these neoantigens change when they go from being subclonal “to being present in most or all of the tumor cells,” he explained. That can occur when a single or few tumor cells acquire a selective advantage. His hypothesis is that these selective events in tumor progression is inherently immunogenic. \

By exploring the fundamental architecture of a tumor, Westcott hopes to learn the mechanisms the tumor uses to evade the immune system.

Ocean breeze

As Westcott settles in at CSHL, he is excited by the overlap between what he sees around the lab and the Maine environment in which he was raised.

“Looking out the window to the harbor feels like New England and Maine,” he said. “It’s really nostalgic for me. Being near the ocean breeze is where I feel my heart is.”

Before his father shared the “Human Genome” book with him, Westcott was interested in rocks and frogs. In high school, his AP biology teacher helped drive his interest in the subject by encouraging discussions and participation without requiring her students to repeat memorized facts. The discussions “brought to life” the subject, he said.

As for his work, Westcott chose to study colon cancer because of its prevalence in the population. He also believes colon cancer could be a model disease to study all cancers. By understanding what differentiates the 12 percent of cases that are responses to immunotherapy from the remainder that don’t respond as well to such approaches, he hopes to apply these lessons to all cancer.

“There is a huge, unmet need,” he said.

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Metro photo

By Daniel Dunaief

Daniel Dunaief

I have never been as happy to hear a Madonna song as I was this weekend.

Let me back up. My family and I attended our second familial wedding of the last three months. This one was a destination wedding in Ithaca, New York.

Stepping out of the rental car at the hotel on campus, I realized I wasn’t in Kansas anymore, as shorts, a T-shirt and a sweatshirt weren’t sufficient for the cooler upstate air.

In the hours before the ceremony on Saturday, my son, brother-in-law, his grown sons and I threw a tiny gift shop Nerf ball around on the baseball field, while surrounded by a visual collage of multi-colored foliage. That tiny football was probably the best $7.50 I’ve ever spent at a wedding.

With the wedding in the hotel, we only had to push an elevator button to get to the correct floor.

The bride and groom exchanged vows that they hadn’t previously shared with each other. Not too surprisingly after dating for close to a decade, the vows included many of the same references to things they each enjoyed about their time together, including dancing in the kitchen while making dinners, watching TV shows together during college, and running to the clock tower and back.

During the cocktail hour, I excused myself from my social circle to go to the bathroom, where I overheard the first of two unusual restroom conversations. The groom and his young cousin were chatting.

“You know the secret to a successful marriage?” the young man asked, eager to share the accelerated wisdom he’d accrued during his short life.

“What’s that?” the groom asked gamely.

“Separate vacations,” the sage young man suggested.

“Hmm, well,” the groom continued, “thanks so much for coming. I appreciate it.”

“My mom said my grandparents would have wanted us to come, so we came,” the unfiltered young man added.

Fortunately, neither of them could hear me inhale sharply.

Listening to the toasts and comments from the parents of the bride and groom, each side seemed to think the new member of the family would help soothe their partner. Perhaps, that says something about the way the bride and groom interact with their parents?

After dinner and before the music started, I returned to the restroom. This time, a man was standing at the sink, washing his hands.

“Out of respect for the gentleman who just walked in, I’m going to end our conversation about poop,” he said to a friend in the stall.

“Oh, uh, I’ll be leaving soon,” I offered, not wanting to interrupt.

“It’s okay,” he added. “We were done.”

Returning to the ballroom, I raced to the dance floor once the music started. My wife, children and I love to dance, with each of us smiling and shimmying as we jump, sway and sing the lyrics of the music. Somehow, our daughter knows the words to just about every song at most of these events, singing and shouting them to her cousin’s girlfriend, who has the same encyclopedic knowledge of modern music. I chime in with the chorus, while our son glides around, often with his arms in the air.

And here’s where Madonna came in. After bending my knees and swaying to numerous rap songs I had never heard before, I was thrilled to hear the familiar intro to a Madonna hit.

Buoyed by throwback sounds from an earlier decade, I threw myself around the floor, crooning for all I was worth.

When the rap songs returned, I scanned the floor and saw the bride, groom and their friends sharing their euphoria for the moment and for their familiar music. While Frank Sinatra never made an appearance, the happy couple were clearly doing it their way.

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Caroline Mota Fernandes Photo by Jonas Nascimento Conde

By Daniel Dunaief

Fungal infections represent a significant health risk for some patients, killing about 1.5 million people globally each year. Doctors struggle to provide medical help for some of these patients, especially those whose weakened immune systems offer insufficient protection against developing pathogens.

Invasive fungal infections, which people typically contract by inhaling them as spores, account for about half of all AIDS-related deaths.

Maurizio del Poeta, Distinguished Professor at the Renaissance School of Medicine at Stony Brook University, has been studying ways to boost the body’s defenses against these potentially deadly infections, even among people with weakened immunities.

Recently, Caroline Mota Fernandes, a postdoctoral researcher in del Poeta’s lab, published research in the journal mBIO, a publication of the American Society for Microbiology, that demonstrated that a heat-killed, mutated version of the fungus Aspergillus conveyed protection in an animal model of an immunocompromised individual.

“The biggest news is that we can simply use the ‘autoclaved’ mutated version,” explained del Poeta in an email. “This version cannot be more dead!”

An autoclave is like a scientific oven: it raises the temperature or pressure. In this case, it can kill the mutated fungus, leaving only the mutated signal that primes the immune system.

The mutated and heat-killed version of the fungus, however, still provided full protection in a condition in a model of a weakened immune system.

“That means this formulation is highly stable and resistant to heat degradation,” del Poeta added.

Del Poeta’s lab had conducted similar research with another fungus called Cryptococcus.

By demonstrating that this approach also works with Aspergillus, del Poeta said the result “validates the cryptococcal vaccine (after all, it uses a mutant of the homolog gene, Sg11 in Crypto and SglA in Aspergillus.”

It also shows that protection exists under an additional type of immunodepression that is different from the one used in the cryptococcal vaccine.

The encouraging results, while in the preliminary stages, are relevant not only for immunocompromised people in general, but also for those who have been battling Covid, as Aspergillus was the cause of death for many patients during the worst of the pandemic.

Homologous genes

Del Poeta’s lab has focused on genes that catalyze the breakdown of steryl glucosides, which scientists have also studied in the context of plants. Crops attacked by various fungi become less productive, which increases the need to understand and disrupt these pathways.

“Folks working with plants started observing that these molecules had some kind of immunomodulatory property,” said Fernandes. “That’s where the idea of this steryl glucosides, which also is medicating fungal virulence, came from.”

The mutation Fernandes studied removed the sterylglucosidase gene sglA. Without the enzyme that breaks up the steryl glucose, the fungus had less hypha, which are necessary for the growth of the fungus. The mutation also changed the cell wall polysaccharides. Mice vaccinated with this heat-killed mutation had a one hundred percent survival rate in response to exposure to the live fungus.

“What was a very great achievement of our work was getting 100 percent protection,” said Fernandes. For immunocompromised people for whom a live attenuated fungus might threaten their health, the effectiveness of the heat-killed mutation proved especially promising.

In the experiment, she administered the vaccine 30 days before exposure, while providing boosters as often as every 10 days.

Fernandes, who started her post doctoral research in del Poeta’s lab in 2018, said several questions remain. “After this study, we are going to try to characterize exactly how this strain induces the immunity and protection to a secondary challenge of Aspergillus,” she said. Dr. Veronica Brauer, another post doctoral researcher in del Poeta’s lab, is conducting this research.

At this point, it’s unclear how long protection against a fungal infection might last.

“For us to estimate the duration of the protection, we have to have a more specific understanding of which immune components are involved in the response,” said Fernandes.

As of now, the mice vaccinated with the mutated and heat-killed fungus had no off target effects for up to 75 days after vaccination.

Fernandes is also working to characterize the mechanism of action of a new class of antifungal drugs previously identified by the lab, called acylhydrazones. She hopes to identify a new virulence protein in Cryptococcus as well.

Collaboration origins

Fernandes, who was born and raised in Rio de Janeiro, Brazil, first worked in del Poeta’s lab in 2013, while she was conducting her PhD research at Federal University of Rio de Janeiro. She was studying antifungal peptides and explained to the Brazilian government why coming to Stony Brook would contribute to her research.

Fernandes started studying fungi when she was in her second year of college at Federal University of Rio de Janeiro.

The daughter of two chemists, Fernandes said she grew up in a house in which she had pH strips, which she used to test the acidity of shampoo, water and anything else she could test. She also entered numerous science fairs.

Fernandes met her husband Jonas Conde, who is a virologist at Stony Brook University and who has studied Covid-19, when they were in nearby labs during their PhD research.

Residents of Port Jefferson, Fernandes and Conde have a four-month-old son named Lucas.

Having a child “motivates me to be better in my work and to set an example for him to be committed in doing some good for other people,” Fernandes said.

Del Poeta described Fernandes as being “extremely effective” in managing her time and has “extraordinary motivation.” He appreciates her commitment to her work, which is evident in the extra papers she reads.

Fernandes appreciates being a part of del Poeta’s lab. She described him as an “amazing” researcher and supervisor and said being a part of his group is “an honor.”

Del Poeta said Fernandes will continue to make mutants for additional fungi, including Mucorales and Rhizopous, for which antifungal therapy is not particularly effective.

Del Poeta added that the urgency of this work remains high. With several other Stony Brook faculty, he has submitted grants to study Sgl1 as a vaccine and antifungal target.

“Imagine [making] a drug that not only can treat the primary infection, but, by doing so, can potentially prevent the recurrence of a secondary infection?” he asked rhetorically. “Exciting!”

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Cell phone etiquette. METRO photo

By Daniel Dunaief

Daniel Dunaief

You’re meeting with your boss, and you can feel your phone vibrating in your pocket with a new text message, an incoming email or a good old-fashioned phone call.

What do you do?

You’d be on pins and needles if someone you knew, your spouse or partner, perhaps, were expecting a baby. Or, perhaps, someone was traveling a great distance through a storm and you were eager to hear that your friend or family member had arrived safely.

But most of the time, the stakes aren’t quite as high with incoming information. In fact, some of the time, we’re getting spam that seeks our attention.

So, when we are talking to our boss, we generally realize that responding to our demanding electronics probably isn’t a great idea.

But what about when we are talking to a parent, a friend, a child or a neighbor?

Given the frequency with which I have seen the tops of people’s heads as they look down at their phones instead of in their eyes, it seems people have concluded that eye contact is so 20th century.

Since when did people outside the room become so much more important and demanding than the ones with whom we are interacting? If we can’t find people who are as interesting in person as the ones far away, perhaps it is time to move to interact with some of those fascinating folks.

I understand that people online don’t have bad breath and messy hair and aren’t wearing the same clashing outfit that they wore last week, and that continues to threaten to give us a migraine.

Maybe we ought to consider classes in electronic etiquette that teachers can share with students or with people who are receiving their first phone.

We can address not only how to handle an incoming text while in the middle of a conversation, but also how to unplug ourselves and our lives from endless messages, games, movies and TV shows.

If I could go back to the time when we handed phones to our children, ensuring that the phone would eventually replace bedtime stories, dinnertime conversation and eye contact, I would consider establishing our own “Ten Commandments” of phone ownership and usage.

These might be:

10. Limit the time each day when you use your phone, with only extraordinarily limited exceptions. If you need to use your phone for schoolwork for two or three hours, that still counts as phone usage.

9. Leave the phone in another room when you’re not using it.

8. If you can’t say something supportive or pleasant on social media, don’t say anything.

7. No anonymous messages or criticism. If you can’t use your name or stand behind what you write, you shouldn’t have written it in the first place.

6. Don’t take embarrassing pictures of your parents and share them with your friends. Older people don’t tend to look as glamorous in digital pictures as younger people, so be kind.

5. Internet fame is not a life goal.

4. When you become better at using your phone than your parents (which occurs in a surprisingly short time), share your wisdom and skills with them. Think of it as familial community service.

3. Don’t assume everything you find online is true. In fact, at least once a week, or even once a day, find something on the internet that you think is false. Use trusted sources to contradict what you think an internet provider got wrong.

2. If it looks like everyone else is having a better time than you, put your phone down. They aren’t.

1. If you can tell your parents to wait while you respond to a text or call from a friend, make sure you tell your friends the same thing when your parents reach out to you.

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Dr. John Clarke. Photo from BNL

By Daniel Dunaief

Live from Upton, New York, it’s … Dr. John Clarke.

While the arrival of the new Occupational Medicine Director and Chief Medical Officer at Brookhaven National Laboratory doesn’t involve late-night comedy, or a live studio audience, it does bring a medical doctor with a passion for bringing his rap and musical skills to a health care audience.

Dr. John Clarke. Photo from BN

Formerly the director of occupational medicine at Cornell University, Dr. Clarke joined the Department of Energy lab as Occupational Medicine Director and Chief Medical Officer for BNL in June..

“My role is to help maintain safety and wellness among the workers,” said Dr. Clarke. “If we have employees who start coming in for some sort of complaint and we see a pattern, that may help us identify who could be at risk of something we didn’t know about that we are detecting.”

A doctor who served as chief resident at New York Medical College in family residency and Harvard University in occupational & environmental medicine, Dr. Clarke said he plans to support a range of preventive efforts.

“I’m excited about the potential to engage in what’s considered primary prevention,” said Clarke, which he defined as preventing a disease from occurring in the first place.

Through primary prevention, he hopes to help the staff avoid developing chronic illnesses such as cancer, while also ensuring the health and responsiveness of their immune systems.

Through physical fitness, a plant-based diet including fruits and vegetables, adequate sleep and hydration with water, people can use lifestyle choices and habits to reduce their need for various medications and enable them to harness the ability of their immune systems to mount an effective response against any threat.

“Modifying your lifestyle is the therapy,” he said. “If you engage [in those activities] in the right way, that is the treatment.”

Dr. Clarke added that the severity and stage of a disease may impact the effectiveness of such efforts. For any vaccine and for the body’s natural immunity to work, people need a healthy immune system.

When Dr. Clarke practiced family medicine, he saw how patients lost weight through a diet that reduced the need for medication for diabetes and high blood pressure.

“Losing weight and staying active does provide a therapeutic impact, where you could be medication free,” he said.

To be sure, living a healthier lifestyle requires ongoing effort to maintain. After reaching a desired weight or cholesterol level, people can backslide into an unhealthier state or condition, triggering the occurrence or recurrence of a disease.

In the vast majority of cases, Clarke said, “you have to make a permanent lifestyle change” to avoid the need for pharmaceutical remedies that reduce the worst effects of disease.

BNL has an exercise physiologist on staff who “we hope to engage in consultations with employees,” said Clarke. He would like the exercise physiologist to go to the gym with staff to show them how to use equipment properly to get the maximum benefit.

BNL already has some classes and various initiatives that promote wellness. “One of the things we’d like to do is coordinate and try to publicize it enough where employees are aware” of the options available at the lab to live a healthier and balanced life, he added.

BNL also has a dietician on staff. Dr. Clarke has not worked with the dietician yet, but hopes it will be part of an upcoming initiative. As he and his staff respond to the demand, they will consider bringing on other consultants and experts to develop programs. 

Covid concerns

Like others in his position in other large employers around Long Island, Dr. Clarke is focused on protecting workers from any ongoing threat from Covid-19.

“We’re still learning more as [SARS-CoV2, the virus that caused the pandemic] evolves,” he said. BNL does a “great job about monitoring the prevalence and the numbers of cases in Suffolk County and among workers.”

Dr. Clarke said he and others at BNL are following the Department of Energy, New York State and Centers for Disease Control and Prevention guidance on these issues.

If the numbers of infections and hospitalizations increase in the coming months, as people move to more indoor activities, BNL may consider deploying a strategy where the lab provides more opportunities for staff to work remotely.

Prior to his arrival at BNL, Dr. Clarke worked as a consultant for a company that was looking to create numerous permanent jobs that were remote.

He suggested that workers need to remain aware of their remote surroundings and shouldn’t work near a furnace or any heater that might release dangerous gases like carbon monoxide. 

Additionally, people should avoid working in areas that aren’t habitable, such as in an attic. Dr. Clarke urges people to notify and consult their employer if they have concerns about working safely at home or on site.

Music vs. medicine

A native of Queens who spent three years of his childhood in Barbados, Dr. Clarke attended Columbia University, where he majored in sociology and music while he was on a pre-med track.

While he was an undergraduate, Dr. Clarke wrote, produced and performed original music. An independent label was going to help secure a major label deal.

He chose to attend medical school at Icahn School of Medicine at Mount Sinai.

Dr. Clarke has championed a program he calls “health hop,” in which he has used rap to reach various audiences with medical care messages. In 2009, he won a flu prevention video contest sponsored by the Department of Health and Human Services for an “H1N1 rap.”

Train commuters may also recognize him from his work for the Long Island Railroad, for which he created a “gap rap.” The public service announcement was designed to protect children from falling into or tripping over the gap between the train and the platform.

Dr. Clarke has produced music for numerous genres, including for a children’s album and a Christian album.

As for life outside BNL, Dr. Clarke is married to Elizabeth Clarke, who is a nurse practitioner and is in the doctorate of nursing practice and clinical leadership program at Duke University.

When he’s not spending time with his wife or their children, he enjoys home projects like flooring and tiling.

Dr. Clarke is pleased to be working at the national Department of Energy lab.“BNL is a great place, because the science and the work they do has an impact,” he said.

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Facebook photo/New York Yankees

By Daniel Dunaief

Daniel Dunaief

If I were pitching to Yankees outfielder Aaron Judge, I would probably take a long pause before throwing my first pitch.

I know it’s absurd to think of this older man who never threw a ball much harder than low high school level pitching to a generational legend, but let’s play out the fantasy for a laugh or two.

I wouldn’t pause so I could figure out how to get him out. Sure, it’d be nice to do my job well and my teammates might appreciate it if I gave us a better chance to win a game.

Instead, I would need to ponder the moment that history might be calling. I’d be thinking about the best choreographed reaction to him hitting a home run. I mean, after all, the pitchers who surrender his long home runs are, in their own way, famous.

They share the moment between when they release the ball, and he obliterates it into the night sky, sending thousands of people screaming out of their seats, arms in the air, sharing in the majesty that wouldn’t be possible without my meatball pitch sputtering, laughably, towards his powerful bat.

If he sent a ball out of the stadium, I would be joining select company, with so many pitchers around the majors surrendering home runs in a historic year.

I’d be thinking about how I’d look in newsreels or newscasts or digital versions of the Aaron Judge year to remember.

I could imagine ways to overreact. I could throw my glove on the mound, gesture wildly by putting my hands in the air, or shake my head so violently that my manager and the trainer would have to waddle out to the mound to put me in a neck brace.

Or, maybe I’d hold my glove up to my face and appear to yell a stream of expletives into my mitt, as if, somehow, I knew I should have thrown a different pitch in a different spot.

Then again, I could rub my fingers in some dirt and write a capital “AJ” on my uniform, like scarlet letters, except it wouldn’t be anything puritanical, and I would be acknowledging my inferiority.

None of that seems like me, even in my fantasy world.

Being stoic would make me too much of a personality-less pitcher. Let’s face it: even in my imaginary moment of being an above average starter or relief pitcher, the time to focus on me would be incredibly short.

Let’s say I didn’t blink after he hit the home run. Or, maybe, I tracked the flight of the ball carefully, like a zebra eyeing a lion suspiciously in the Serengeti. That might get me on TV and make me more than just another guy who gave up a home run to Aaron Judge.

Maybe I’d wait at home plate and give him a high five or a fist bump to acknowledge a full season worth of greatness. While kids do that in Little League, professional players generally don’t acknowledge the remarkable achievements of their opponents.

When he reached second base, I could put down my glove and clap from the mound, ever so briefly. Then, perhaps, I’d take off my hat and salute him.

Or, maybe I could take a page out of the more subtle but celebrated Mona Lisa textbook. I could give just a hint of a smile as if I were saying, “you beat me and you’re a pretty spectacular hitter. There’s no shame in losing this battle and now we’re weirdly connected, like we’re kind of twins, except that you’re great and going to be remembered forever and I’m just going to be remembered for starting the ball on its magical journey into the history books.”

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Babak Andi holds a 3-D model of the coronavirus responsible for the COVID-19 pandemic. Photo courtesy of BNL

By Daniel Dunaief

For close to two and a half years, the world has had a microbial enemy. The SARS-CoV2 virus, which causes Covid-19, has resulted in close to 6.5 million deaths, caused lockdowns, restricted travel, closed businesses, and sickened millions. The key to fighting such a dangerous enemy lies in learning more about it and defeating its battle plan.

Working with principal investigator Daniel Keedy, Assistant Professor at the City University of New York and Diamond Light Source in the United Kingdom, Babak Andi, who is a beamline scientist from the structural biology group at Brookhaven National Laboratory, spent over two years studying a key viral enzyme.

Recently, the researchers revealed the structure at five temperatures of an enzyme called Mpro, for main protease. This enzyme, which separates proteins the virus makes, is critical for the maturation of the SARS-CoV-2 virus particles. They published their work in the Journal of the International Union of Crystallography (IUCrJ).

Using the Frontier Macromolecular Crystallography (FMX) beamline at the National Synchrotron Light Source II at BNL, Andi collected data on the structure of the enzyme at temperatures ranging from 100 degrees Kelvin, which is about negative 280 degrees Fahrenheit, all the way up to 310 degrees Kelvin, which is normal body temperature. “Nobody had done that, specifically for this protein,” said Andi.

Keedy, who guided the data collection, processed the information and wrote most of the paper, described the effort as a “great collaboration.” The gradual change in the conformation of the enzyme helped the scientists learn how it may move or shape-shift in general, he explained.

Keedy had worked with BNL in the past and pursued research at the FMX beamline because the scientists at BNL had “been working with Mpro on site, and were very approachable and open to the idea.”

Finding the specific structure of important proteins like Mpro can help researchers, pharmaceutical companies and doctors search for inhibitors or small molecules that could be specific to these proteins and that might interfere with their function.

Andi and other scientists at this beamline worked through the pandemic shutdown because of the potential practical application of what they were doing.

“We almost had all the infrastructures in place to allow other scientists to connect and operate the beamlines remotely, enabling them to collect data on Covid-19 virus proteins,” said Andi. “In my opinion, being able to support all the academic and industrial scientists to collect data for Covid-19 research was our greatest achievement during the worst period of the pandemic.”

While coming into the lab in those early months raised concerns about their own health, Andi and his colleagues, who developed safety protocols, felt an urgency to conduct this research.

“When Covid hit, we had a sense that this is our duty, this is our job to contribute to this field, to make sure that every scientist who works on Covid-19 had easy access to our beamlines, facilities and all the tools [necessary] to make new drugs,” said Andi. 

How they solved the structure

The technology for the beamline enables Andi and other scientists to collect data quickly and even remotely. Speed helps because the longer x-rays hit a protein, the more likely they are to cause the kind of damage that makes determining the structure difficult, particularly at higher temperatures.

The first step in this research was in producing this protein, which Andi’s collaborators at BNL in the biology department provided. The biology department also helped with crystallization.

Andi prepared the beamline and aligned the x-ray beam, which are necessary to collect data.

The scientists rotated and moved the crystal through the x-ray, distributing the beam over the length of the crystal to minimize radiation damage.

The small size of the x-ray beam made it possible to keep the beam focused on the smallest dimension of the structure. The researchers studied the crystal at five different temperatures, starting at cryogenic all the way up to physiological.

Of the 195,000 structures listed in the Protein Data Bank, or PDB, only five had been determined at body temperature. That includes two from the group of collaborators who participated in this study.

Andi collected three or four data sets at each temperature.

“The different conformations we saw may inspire a new twist on antiviral drug development that targets a different place in the protein, but with a similar or better effect,” Keedy explained.

The researchers did not include other factors that might affect the conformation of the protein, such as pH, pressure, the number of ions or salts in the environment, among others. For the Mpro protease to work, it has to bond to another similar protein, forming a dimer.

Andi said the Pfizer treatment Paxlovid binds to the active site of this enzyme, inactivating it.

The drugs he is looking for are similar, although he is also searching for other places on the enzyme besides its active site.

Keedy hopes to try to make a monomeric form of the enzyme through a mutation. He could then find drug-like small molecules that target the exposed interface between the two copies.

BNL origins

After he completed his PhD and post doctoral work at the University of Oklahoma, Andi started his career at BNL 11 years ago as a post doctoral researcher.

During his childhood, Andi was initially interested in astronomy. When he enrolled at a university outside the United States, he took an entrance exam.

“Based on your score, it tells you which discipline of science you can go into,” he said. His score directed him to the field of cell and molecular biology.

“I’m happy this happened,” he said. “I find that I’m actually more interested in molecular biology than in astronomy.”

Outside of work, Andi enjoys do-it-yourself projects. Astronomy also continues to appeal to him, as he is fascinated with astrophotography and reads astronomy articles.

As for the work with a Covid enzyme, Andi hopes he has other opportunities to contribute. 

“I am interested [in continuing] the research in this field,” he explained. “That depends on time, resources and current or future priorities.”

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Twilight Zone. Pixabay photo

By Daniel Dunaief

Daniel Dunaief

Conversations with friends, relatives and neighbors have taken a turn into “The Twilight Zone” episodes recently.

Decades ago, when I spoke with my friends, we discussed our activities, ambitions and plans. We might have complained about our bosses, described a business trip, shared an encounter with a stranger on a plane or train, or described our frustrations with our favorite sports teams.

Sure, we still do that, but, as the years pass, the discussions drift. This is where I’d cue the music.

In Episode One, we have two college friends who shared a room for several years, who sweated through a spectacularly hot summer in Boston with no air conditioning, and who, over the decades, visited each other’s homes with and without our wives and children.

So, these two friends recently started catching up.

“I can’t stand the hair that’s coming out of my ears,” I offered. “It makes it harder to hear and to be taken seriously by anyone looking at me.”

“Yeah, that’s pretty unwelcome,” my friend laughed. “My back is killing me. I wake up every morning and it takes me a while to feel comfortable enough to stand and shuffle to the bathroom.”

“My hip has been a problem,” I reply.

“I also don’t see particularly well. I don’t like driving when it’s dark,” he added.

“My knee is sore,” I added, “but I think that’s from compensating for my hip.”

And so it went, for about 10 minutes, until we broke the description of all that ails us and transitioned to a discussion of all that inspires, and worries, us about our college-age children.

“I hope you feel better soon,” I offered as we got off the phone.

“At this point, I’d just take not feeling worse,” he said.

Okay, so that wasn’t too terrifying, right? Two 50-ish guys chatted and shared personal details about the aging vessels that carry us through life.

That takes us to Episode Two. Imagine, if you will, a group of older adults, representing the 50ish and the 80ish generation, chatting in person together.

“Have you been to the doctor recently?” one of the people asked.

“Which one? For what?” a second one replied.

“How many doctors do you have?” a third one asked.

And that is where the conversation became a competition. Each person, slowly and deliberately, shared the number of doctors he or she visits.

“I’ve had kidney stones, so I have a urologist,” I offered, as if I were recounting trophies on a shelf or comparing the number of friends I have with someone else in fourth grade rather than recalling a specialist who helped me deal with excruciating agony.

“Do you have an ENT doctor? I have one,” someone else said.

My competitive spirit again got the best of me.

“I have the best GI guy, who gave me a great colonoscopy. I had such a nice rest while I was under anesthesia,” I said.

I pictured a younger version of me, sitting with the group, staring, open-mouthed at the enthusiasm with which all of us, me included, counted our doctors and the reason we needed them.

In Episode Three, a man in his 30s walked his dog, limping along with a supportive black boot on his leg. Another man (me) appeared, pulled along by his oversized dog.

“Not to get too personal,” I said, “but your shoes don’t match.”

The good-natured man smiled and said he thought he had shin splints from running, but discovered he had a hairline fracture that required several weeks of rest in a boot.

“I went to my parents’ house in New Hampshire and ran over five miles on an uneven road. The next day, I could barely move. I have to rest it for six weeks,” he said.

I nodded and wished him a speedy recovery.

“Well, maybe it hurts just because I’m older,” he offered.

You have no idea, I thought, as I could feel the urge to hold back a clock that pushes each of us forward through time. 

Cue the music.

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From left, Chang Kee Jung, Barry Barish and Carl Lejuez. Photo by John Griffin/Stony Brook University

By Daniel Dunaief

Albert Einstein predicted gravitational waves existed, but figured interference on the Earth would make them impossible to observe. He was right on the first count. On the second, it took close to a century to create an instrument capable of detecting gravitational waves. The first confirmed detection, which was generated 1.3 billion light years away when two black holes collided, occurred in September of 2015.

For his pioneering work with gravitational waves, which now include numerous other such observations, Barry Barish shared the Nobel Prize in 2017 with physicists Rainer Weiss and Kip Thorne.

In the fall of 2023, Barish is bringing his physics background and knowledge to Stony Brook University, where he will be the inaugural President’s Distinguished Endowed Chair in Physics. Barish will teach graduate students and serve as an advisor to Chang Kee Jung, Chair of the Department of Physics and Astronomy and Distinguished Professor.

From left, Barry Barish and Chang Kee Jung. Photo by John Griffin/Stony Brook University

“I’m really happy,” said Jung in an interview. “Nobel Prize winning work is not all the same. This work [Barish] has done with LIGO [the Laser Interferometer Gravitational-Wave Observatory] is incredible.”

Jung suggested the discovery of these two merging black holes “opened up a completely new field of astronomy using gravitational waves.” The finding is a “once-in-a-generation discovery.”

Gravitational waves disrupt the fabric of spacetime, a four-dimensional concept Einstein envisioned that combines the three dimensions of space with time. These waves are created when a neutron star with an imperfect spherical shape spins, and during the merger of two black holes, the merger of two neutron stars, or the merger of a neutron star and a black hole.

Jung suggested a way to picture a gravitational wave. “Imagine you have a bathtub with a little rubber ducky,” he said. In the corner of the bathtub, “you slam your hand into the water” which will create a ripple that will move the duck. In the case of the gravitational wave Barish helped detect, two black holes slamming into each other over 1.2 billion light years ago, when life on Earth was transitioning from single celled to multi celled organisms, started that ripple.

While Barish, 86, retired after a lengthy and distinguished career at CalTech in 2005, Stony Brook has no plans to create a team of physicists who specialize in this area. “The most important thing is that people together exchange ideas and figure out what to do next that’s interesting,” Barish said in an interview. “I’ll keep doing gravitational waves.”

Instead of encouraging graduate students and even undergraduates to follow in his footsteps, Barish hopes to “help stimulate the future here and help educate students,” he said.

An important call

Jung, who became chair of the department in the fall of 2021, has known Barish for over three decades. On a periodic informal zoom call, Jung reached out to Barish to tell him Stony Brook had offered Jung the opportunity to become chair. Barish suggested he turn it down. As Jung recalled, Barish said, “Why do you want to do that?”

On another informal call later on, Jung told Barish he decided to become chair, explaining that he wanted to serve the university and the department. Barish asked him what he would do as chair. Jung replied, “‘I would like guys like you to come to Stony Brook. It took [Barish] about 10 seconds to think about it and then he said, ‘That’s possible.’”

That, Jung said, is how a Nobel Prize winning scientist took the first steps towards joining Stony Brook.

Last week, Barish came to Stony Brook to deliver an inaugural lecture as a part of the newly created C.N. Yang Colloquium series in the Department of Physics and Astronomy.

Stony Brook officials were thrilled with Barish’s appointment and the opportunity to learn from his well-attended on-site lecture.

In remarks before Barish’s packed talk at the Simons Center Della Pietra Family Auditorium, Carl Lejuez, Executive Vice President and Provost, said he hears the name C.N. Yang “all the time,” which reflects Yang’s foundational contribution to Stony Brook University. “It’s fitting that we honor his legacy with a speaker of Dr. Barish’s character who, like Yang, is also a Nobel Prize winner. It’s a really nice synergy.”

Indeed, Yang, who won his Nobel Prize in 1957, coming to Stony Brook “instantaneously raised the university profile,” said Jung, whose department is the largest on campus with 75 faculty.

Surrounded by a dedicated team of scientists, and with the addition of another Nobel Prize winner to the fold, Jung believes the team will continue to thrive. 

“If you put together great minds, great things will happen,” he said.

Seeing the bigger picture

Barish is eager to encourage undergraduates and graduate students to consider the bigger picture in the realm of physics.

“[In general] we train graduate students to do something really important by making them narrower and narrower and narrower, so they can concentrate on doing something that’s worthy of getting a thesis and is as important as possible,” Barish said. “That works against creating a scientist who can look beyond something narrow. That’s bothered me for a long time.”

The problem, Barish continued, is that once researchers earn their degree, they continue on the same path. “Why should you happen to have had a supervisor in graduate school determine what you do for the rest of your life?” he asked.

Once students have the tools of physics, whether they are experimental or theoretical, they shouldn’t be so locked in, he urged. “It’s possible to use these same tools to do almost any problem in physics,” Barish added.

His goal in a course he plans to teach to advanced graduate students (that’s also open to undergraduates) is to provide exposure to the frontiers of science.

A few years ago, Barish recalled how the New York Times ran a picture of a black hole above the fold. He taught a class how scientists from around the world combined radio telescopes to make it act like one radio telescope the size of the Earth.

Helping students understand how that happened “pays off in the long run in making our physics students that we turn out be broader and more interesting and more interested in physics,” Barish said.

When Barish arrives next September, Jung said he plans to have some assignments for interactions with undergraduates. “Undergraduate research is critically important,” Jung said. Barish will also interact with various student groups, as well as the community outside the university.

“We will create those opportunities,” Jung said.

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Queen Elizabeth II. Pixabay photo

By Daniel Dunaief

Daniel Dunaief

During the Platinum Jubilee for Queen Elizabeth II to celebrate the monarch’s 70 years on the throne, Clary Evans, a radiation oncologist who works at Northwell Health, her husband Tobias Janowitz, a scientist at Cold Spring Harbor Laboratory, and their families got together with another English family to mark the occasion.

They made a cake and had tea, “aware that this was probably the last time” they would celebrate Queen Elizabeth’s lengthy legacy, Evans recalled in an email.

Residents of Suffolk, England, Evans’s parents Philip and Gillian shared memories and thoughts on Queen Elizabeth II, who died last week at the age of 96.

Before Elizabeth’s coronation at the age of 27, Philip Evans, who was a teenager, traveled with his brother Anthony to Trafalgar Square, where they camped out near the fountain.

After a night filled with an early June rain in 1953, Evans and his brother awaited the moment to see the queen, whose coronation occurred 16 months after she became queen.

Gillian and Philip Evans with their Patterdale terrier puppy in Mettingham, Suffolk, UK in August of this year. Photo from Clary Evans

The next morning, as crowds continued to grow, the police pushed the newer arrivals in front of the group, which meant Phillip was in the third tier of onlookers.

Through the crowd, he caught a glimpse of the young queen, offering a stiff wave to her subjects.

“It was a marvelous thing to do,” Evans said by phone from his home. The travel and waiting in the rain meant it “wasn’t easy.”

Gillian Evans, meanwhile, traveled with her family to visit her aunt, who, at the time, was the only one in her family who owned a television.

“It was lovely to see what a beautiful spectacle it was,” Gillian Evans said.

The queen executed her duties admirably under an intense spotlight that never dimmed during her over 70 years of service, she added.

“What a remarkable lady she had been,” Gillian Evans added. “She said she would give herself to the nation for as long as she lived, and she did. Right up to the very, very last, which is wonderful.”

While Gillian Evans thought such conditions were akin to being in  prison, with all the limitations and the constant responsibilities, she believed the queen “loved it. It showed in her face.” Being a part of a “love match” with her husband Prince Philip “must have helped enormously.”

The Evans matriarch, 83, who is a retired diagnostic radiographer, is amazed at the effect the queen’s death is having on residents.

Philip Evans, who said the queen did “jolly well,” recognized that the queen made mistakes, one of which arose during her muted reaction to the death of Princess Diana in a car crash in 1997.

“She had a really bad time when Princess Diana was killed,” said Philip Evans, who retired in 2000 as a general surgeon. “She was just pulled down by the power of the press. In legalese, ‘she was badly advised.’”

During a recent visit to the ophthalmologist, Evans chatted with three people about the queen and her son Charles, who has now become King Charles III.

People were saying “the queen had done a good job” and that they believed her son was “well suited” for his new role.

Philip Evans has noticed that the church bells ringing in the aftermath of her death don’t have their typical sound.

The sound alternates between loud and muted. The churches are using a so-called half-muffled peal, which creates a somber echo. The bells rang the same way last year after Prince Philip’s death.

“It’s very alarming and tells you that something is odd,” Evans said.

As the country prepares for the funeral of a queen born eight years after the Spanish Influenza pandemic of 1918 and who died two years after COVID-19, Clary Evans recognized that Queen Elizabeth II was a “link to those values of duty and service that were strong in those war and post-war years.”

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