CLOSE
Tags Posts tagged with "Daniel Dunaief"

Daniel Dunaief

by -
0 355
Pixabay photo

By Daniel Dunaief

Daniel Dunaief

We have friends who live close to us who are pregnant. Okay, that sounds weird, right? She’s pregnant, and he looks sheepish, like he’s not sure what’s coming.

That’s not entirely fair. He was socially awkward before he brought his small package of genetic material to the pregnancy party. Why would anyone imagine he would be any different in the months before he makes a head first dive down the rabbit hole into the wonders and challenges of parenthood?

Now, if their families are anything like others I’ve known, they are bound to have a wide range of pre and post delivery discussions.

“Are you going to name the baby after my side of the family?”

“Make sure you put sugar, spice and everything nice in the crib or the baby will become colicky like your Aunt Michelle. She was one of the most miserable babies we’ve ever seen and that’s because her mother forgot about the sugar and spice under the crib.”

One of the most fascinating and sometimes confounding parts of the baby discussion, which can extend well into the years that follow, is the family credit for various traits.

To wit, “He’s incredibly serious and focused just like his Uncle Oswald. That Oswald was a man with a purpose from the time he was born, just like your little baby Joey.”

Or maybe, “Morgan has the same broad smile, laugh or sense of humor as her Aunt Carol.”

Each family can dig in, sharing ways that the developing child has characteristics they are convinced come from one side of the family, often from the speaker who has a proprietary interest in propagating the enduring myth of a family heritage.

Such talk suggests somehow that heredity is much more important than environment. The credit can go beyond physical characteristics such as long eyelashes, rounded shoulders, or sparkling eyes: they can include artistic talent, an ability to relate to other people, or a proficiency for languages.

That somehow seems un-American. After all, we the people generally believe that hard work can help people become proficient in any area, developing the kind of talent that differentiates them in their field and allowing them to control their destiny.

Such strong genetic links, while providing an appealing way to connect to ancestors and to those who aren’t around to smile and play with their descendants, is akin, if you’ll pardon the pun, to linking someone’s last name to their profession.

“Oh, the Jones family? Sure, they all became teachers. The Berringtons went into the clothing business, while the Shimmers all became dentists. They all have such gifted dental hands.”

Such blanket statements about where someone’s exceptionalism originated also throws the other sides of the family into the shadows, as if their only role were to ensure the ongoing survival of the dominant and more important family tree.

Family trees, however, like the trees that people decorate around this time of year, have bilateral symmetry, with people decorating each side in popcorn, cranberries and/or holiday lights.

Rarely does anyone do a deep dive into the other side of a family, learning whether the Jones family had faster legs, a quicker wit, better grades or a stronger work ethic.

Then again, the point of these claims isn’t to be scientific, thorough or even fair. It’s a way to connect the children of today with those who came before. Even if people don’t believe in reincarnation, focus on genes, or contemplate the enduring qualities of any family culture, they might feel tremendous joy and comfort hoping that this person’s unwritten life includes future chapters that reflect a familial past that need not be exclusive to one branch, one side or one person.

Story weaving may help give a developing life context and meaning. Ideally, those attributes and connections may remind the family and this new person about the kind of strong and accomplished roots that can help him or her develop into the kind of person he or she chooses to be, which would be a win for everyone.

by -
0 368
Pixabay photo

By Daniel Dunaief

Daniel Dunaief

Rufus is not sure what to do. He’s never there first. He circles the yard carefully, looking back at the fence. Bob sits in his usual seat at the picnic table, talking on his phone.

He doesn’t want to run before the others arrive. He sits under a tree, closes his eyes and allows the smells to fill his ample nostrils.

“Hi,” chirps Peanut, jumping up to reach his face. “Hi, hi, hi, hi!”

“Back up,” Rufus barks, “you’re too close.”

“Sorry, sorry, sorry, sorry,” she says. Peanut repeats herself in that high tone that annoys Rufus. “Even though I can’t see red or green, I know that holiday sweater is hideous,” Rufus said.

Fifi lowers her head.

“On the plus side,” he adds, “your fur looks great.”

Fifi prances in approval. She likes it when others notice that she’s been to the groomer.

Rufus glances at Andrea, Fifi’s human. He likes the way she scratches his ears and looks directly in his eyes.

Finally, the rest of the crew races over, tongues hanging out, fur flying off Oscar as he skids to a stop.

After the customary butt smelling, Oscar, the golden retriever, speaks.

“You had Uncle Doug’s sweet potato?” he asks Cole, an apricot poodle. “Does that taste as good as it smells?”

Cole barks his agreement, although he eats it so quickly he barely tastes anything. “And you had asparagus,” Cole says to Rufus.

Rufus sticks out his tongue. He doesn’t get his usual treat from Bob during Thanksgiving unless he has a few pieces of asparagus, which he hates.

“Stories?” King demands.

A French Mastiff, King regularly reminds the group he has the shortest life expectancy so he can’t waste time on food chatter.

“Bob’s got a new girlfriend,” Rufus starts. “She reminded him to walk me earlier than usual. She makes him shut the bedroom door, but she makes up for it by giving me more leftovers.”

“Nice,” barks Roxie. “Glad someone had a good holiday.”

“What? What? What?” barked Peanut.

A basset hound, Roxie hates her name and her short legs. Her ears also annoy her because they fall in her water when she drinks

“My family had a huge gathering,” Roxie barks. “These new kids thought they could teach me to fetch. I don’t fetch. Do they think I’m a golden retriever?”

“Hey!” Oscar barks.

“No offense,” Roxie adds. “What about you?”

“Aunt Linda spent the entire dinner saying she shouldn’t eat garlic. She didn’t listen to herself and was in the bathroom for an hour, groaning and cursing. How about you, Cole?”

Cole is among the tallest dogs at the run, particularly after he went to the stylist. Cole wanders over to the water bowl, with the rest of the group following closely.

“Cole?” Fifi asks. It is one of the rare times she doesn’t repeat herself.

“We watched movies in the dark,” Cole shrugs.

“There’s more,” says Rufus. “What’s going on?”

“Audrey looked out the window and wiped her eyes all weekend,” Roxie says. “She kept whispering how much she missed her brother.”

“What happened?” Oscar asks.

“I don’t think she’s going to see him again,” Cole says. “When I leaned into her legs, she ran her wet hand over my face. Other than a few walks, she spent most of her time on the couch. She barely ate, so I didn’t eat much, either.”

“Sad, sad, said,” barks Fifi.

Rufus agrees.

“You did what you should have done,” King says, the folds under his lips turning down. “You’re going to help her and we’re going to need to help you.”

“Help? How?” Oscar asks. Whenever Oscar became anxious, he circled the water dishes at the run. He knocks one over.

“My bad,” he says.

“Cole drinks first,” King says. “And we let Cole go to Andrea before the rest of us. We all know she’s the favorite human.”

Fifi nods, indicating she would share.

“How about you, King?” Rufus asks.

“It was great,” King says. “My family welcomed a new baby. At first, they kept me away, but they slowly let me see him. We’re going to be friends.”

“How do you know?” asks Cole.

“He touched his hand to my nose. It was soft and wonderful. He made me feel so young,” King adds.

by -
0 714
From left, Daisy Zavala, Stacey Scott and Krishna Veeramah Photo by John Griffin/Stony Brook University

By Daniel Dunaief

They can’t tell you whether the leading current presidential Republican and Democratic candidates demonstrate signs of cognitive decline or, for that matter whether any real or perceived cognitive decline is greater for one than the other.

Researchers at Stony Brook University, however, have conducted recent studies that may act as a platform to generate a measure of cognitive age that differs from chronological age.

Associate Professors Krishna Veeramah and Stacey Scott and graduate student Daisy Zavala recently published research in the Journal of Gerontology: Biological Sciences in which they studied a combination of cognitive testing done over different time periods and blood tests.

Indeed, the combination of looking at signs of epigenetic changes, or alterations in the environment that affect the way genes work, and studying the effectiveness and variability of tests of memory has the potential to offer some clues about how chronological age may differ from cognitive age. At this point, the scientists have been exploring that relationship, while future work may address not just what is happening, but also why.

Among the data from 142 subjects who took a host of learning tests from 2012 to 2016 during different time periods in the day, increasing epigenetic age was linked with poorer average processing speed and working memory, as well as with greater variability in test performance.

While the statistical analysis accounted for the fact that increasing chronological age had an effect, biological age had an even bigger impact, Veeramah, who is in the Department of Ecology and Evolution and a population geneticist at Stony Brook University, explained.

The study, which Veeramah described as an “early/pilot study,” and will require further follow up, offers another perspective on the different impacts the aging process can have on cognitive function.

The results matched the scientists’ prediction, which was that people who had greater epigenetic age acceleration processed information more slowly and had poorer memory performance on average across the study.

These individuals were not only performing more poorly on average, but were also more variable in their performance.

“This should give us pause about making judgments about people related to their age and what that means about their abilities,” said Scott, who is in the Psychology department.

This study suggests that “how old you are doesn’t tell you so much about how well you’re doing in your cognitive function,” said Scott. Theoretically, the extent to which a person’s body is older than a chronological age could be an indication of what might accelerate or decelerate cognitive function, although longitudinal studies will test this.

The researchers believe this study will contribute to a body of work that is trying to see if researchers can reliably identify biological age acceleration and, if so, how to slow it down.

Testing design

The researchers gathered data from participants who took tests on smartphones provided to them. These phones didn’t receive calls or messages and didn’t have access to the web.

Participants took tests during different times in the day. About 60 percent of study participants were African American and 20 percent were Hispanic/Latino. They also varied in household income, with most participants earning between $20,000 to $60,000.

In one test, people saw symbols at the top of the screen that they had to match with symbols at the bottom as quickly as possible. In another test, people viewed three red dots on a grid for a few seconds. They were distracted by searching for “E’s” and “F’s” on a screen and then had to place the dots back in their original place on the grid.

Participants completed dozens of tests over two weeks, offering a profile of their performance during different times of the day, situations and activities.

By testing people under various conditions, the researchers could get a more comprehensive, complete and realistic understanding of their cognitive state, which also reflects the way people experience a range of competing stimuli.

The scientists were profiling people “in terms of good and bad days” to get an understanding of their “typical performance,” explained Scott.

The SBU scientists suggested that inconsistency was increasingly proposed as a potential early indicator of dementia.

The “unique aspect” of what these scientists did is comparing epigenetic data to ambulatory cognitive measurements, rather than cognitive tests in a lab setting, Veeramah said.

To test the epigenome, Veeramah explored the degree of methylation of DNA from a single blood sample from each participant using a microarray to look at about a million positions in the human genome.

Adding a CH3 group, or methylating, genes tends to make the DNA coil more tightly, making it less likely to interact with other molecules that might turn it on.

Some parts of DNA show changes in methylation that correlate with age, while others are dependent on other things like the environment or specific cell type.

The underlying assumption is that cells pick up more damage and this includes the DNA sequence with time.

Zavala’s dissertation extends this work to look at more long term implications on cognitive health.

Zavala’s research “looks forward,” Scott explained in an email. “Does someone’s epigenetic age acceleration now at the beginning of the study predict their cognitive performance up to three years later?”

Dinner and a hypothesis

Veeramah and Scott, who got married in 2020, decided to combine their expertise for a research project.

“We were talking about our work over dinner and we thought about what I do and the kind of data we have from this existing sample of people” who participated in this cognitive study, said Scott.

The couple wrote a small grant to the research foundation at Stony Brook, which provided seed funding for this study.

Veeramah, whose research covers a broad scope of topics, suggested that the concept of studying these clocks is a fairly new area.

Researchers have been testing whether obesity, Alzheimer’s, and other factors could correlate with the internal environments that cause the kind of wear and tear often associated with aging.

by -
0 515
A Thanksgiving postcard. Photo courtesy Kenneth C. Brady Digital Archive

By Daniel Dunaief

Daniel Dunaief

Sending a text message to friends and family half way around the world and then getting an instant response is pretty incredible, shortening the distance between any two people.

And yet, as Thanksgiving approaches, I appreciate some of the earlier, albeit slower at times, elements of my younger years.

Take, for example, the postcard. Sure, people still send them, but postcards and letters are not as necessary or, in many cases, even considered. Even if people don’t send us texts, we can follow them on any of the social media sites where they’re showing us how they’re having the time of their lives and eating incredible food.

Over three decades ago, when my father died, I remember the exquisite and bittersweet pain from seeing the handwritten notes he’d left for himself. He didn’t have a smart phone where he could make electronic lists. Reading his pointed and slanted script was so deeply personal that I felt as if the letters and words connected us.

Once, years before he died, my father flew for a business trip. Eager to write to me and without any paper, he took out the barf bag from the seat in front of him, wrote about his travels and shared some dad humor, put it in an envelope and mailed it. I remember smiling broadly at the words he shared and the unconventional papyrus he’d chosen to carry those words.

The modern world of digital pictures and digital cameras gives me the opportunity to relive numerous experiences. I can easily sort those images by year and location, without needing to buy an album, find the right sequence of photos and slip them behind the translucent cover.

Still, remember when we used to bring rolls of film to the drug store for them to develop? We’d come back two or three days later, open up the often small green envelope and pour through the photos, wondering what we caught, what we missed and how the image compared with our memory.

The hit-or-miss nature of those photos made the imperfections somewhere between disappointing and perfect. They were real moments, when hair got in our eyes, when we shared our disappointment about a birthday present, or when we spilled a container of apple juice as we were blowing out candles.

What about all those photos from people in the early part of the 20th century? Didn’t they look utterly miserable? Was it the shorter life span, the challenging early days of the camera, bad dentistry and orthodonture or, perhaps, a culture that hadn’t yet suggested saying “cheese” or smiling for the camera?

My theory on those miserable faces, though, is that the pictures took so long to prepare amid challenging weather conditions — it was too hot to wear that overcoat — that people wanted the process to end so they could stop trying to hold a squirming child or ignore the need to scratch an itch.

Maybe I grew up in the sweet spot, where pictures weren’t instant but were easy enough to take that they didn’t require endless retakes. Yes, I have friends and relatives who insisted on taking 37 shots of the same moment, just in case someone was closing their eyes, which triggered the kind of fake smile in me that I recognize in my children when they’re eager to be somewhere else, doing something else, and, most likely, looking down at their phones to see pictures of other people.

This Thanksgiving, I appreciate not only the gifts of the present, with the endless storage space on my phone and the ability to capture life in real time, but also the perspective from a past, where the anticipation of seeing a snapped photograph or receiving a postcard turned the pictures into keepsakes and memory gifts.

by -
0 730
From left, Joshua Rest and Jackie Collier. The blurred image in the background shows the genome structure of Aurantiochytrium limacinum, including the arrays of rDNAs at the chromosome ends, and the two mirusvirus elements that were discovered. Photo by Donna DiGiovanni

By Daniel Dunaief

They were trying for two years to solve a puzzle that didn’t make sense. Then, a combination of another discovery, some extensive analysis, and a deep dive into the past helped them put the pieces together.

Jackie Collier, Associate Professor at the School of Marine and Atmospheric Sciences at Stony Brook University and Joshua Rest, also an Associate Professor in the Department of Ecology and Evolution at Stony Brook, had been looking closely at the genetic sequence of a marine protist called Aurantiochytrium limacinum. A circular section and pieces at the end of the chromosome seemed inconsistent with the rest of the genes and with the specific type of single-celled organism.

But then, they saw a preprint of a paper in 2022 that the prestigious journal Nature published earlier this year that described a new type of virus, called a mirusvirus, which appeared to have genetic similarities and a signature that matched what they saw in their protist.

Mirus means “strange” or unknown in Latin, which was a way to describe the unusual evolutionary traits of these viruses.

Collier and Rest, working with a group of collaborators, found that a high copy circular structure and genetic elements that integrated at the end of one chromosome resembled this mirusvirus.

“From the perspective of the virus folks, ‘mirus’ was apt because the mirusviruses contain features of the two very distinct ‘realms’ of viral diversity,” Collier explained. “Our results confirm that strangeness, and add more strangeness in terms of two different ways to maintain themselves (circular episomes or integrated into a chromosome) in the same host genome.”

Researchers had discovered the mirusvirus by sequencing DNA they took from the ocean. “What our findings do is connect to a host and hopefully eventually prove that there is a protist that contains a mirusvirus genome,” said Collier.

The Aurantiiochytrium protist, which is part of the Thraustochytrids order, intrigues researchers in part because it produces essential omega-3 fatty acids and carotenoids, which enhances its biotechnology potential. This protist also intrigues Collier because it is involved in decomposing dead mangrove leaves in mangrove forests.

Dormant virus

The Stony Brook scientists have been working on analyzing the genome for a paper they recently published in the journal Current Biology since 2019.

“We had been struggling to figure out what that was,” said Collier. “We had a lot of hints that it had some relationship to some kind of viruses, but it wasn’t similar enough to any known virus. We were struggling to figure out what to call this thing,” which they had tentatively designated CE1, for circular element one.

Identifying viral elements provided the “hook” for the paper.

Rest suggested that the different confounding elements in the protist genome came from two different viruses.

At this point, Collier and Rest think the virus may be something like the herpesvirus, which hides out in human nerve cells. That virus enters a latent phase, remaining quiescent until a host becomes stressed.

John Archibald, Lucie Gallot-Lavallee and others from Dalhousie University in Canada, who are collaborators on this study, are creating the kind of conditions, such as lower food or colder temperatures, that might reactivate the viral DNA, causing it to release viral particles.

The research team has detected similar mirusvirus proteins in other Aurantiochytrium isolates and in four other Thraustochytrid genomes. 

Focusing on this protist

Collier started working on thraustochytrids in 2002, after the first outbreak of QPX disease in Raritan Bay hard clams.

Bassem Allam, who is now the Marinetics Endowed professor in Marine Sciences at SBU asked Collier if she would help understand what was going on with the clams which had QPX disease. That was caused by another Thraustochytrid.

The organism that caused QPX is a relative of the protist that interested Collier.  She chose Aurantiochytrium in part because it was the easiest to grow.

When the Gordon and Betty Moore Foundation started a program to develop molecular genetic methods for diverse marine protists about seven years ago, Collier approached Rest for a potential collaboration.

A key piece, half a century old

In her informatics work, Collier followed a path that Google or artificial intelligence might otherwise have missed.

Like traveling back hand over hand in time through older research, Collier pulled up the references from one study after another. Finally, she found an intriguing study from 1972 that had overlaps with their work.

Scientists had isolated a Thraustochytrid from an estuary in Virginia using the same kinds of methods Collier and Rest used to grow Aurantiochytrium. Using electron microscopy, these earlier researchers characterized its ultrastructure. Along the way, these 1970’s scientists noticed that starved cells released viral particles, which Collier and Rest believe might be the first record of a mirusvirus.

The researchers wrote a short paper that the prestigious journal Science published.

A cat connection

While Collier, who lives in Lake Grove, and Rest, who is a resident of Port Jefferson, are collaborators at Stony Brook, they have also have a feline connection.

In the beginning of the pandemic, a feral cat delivered kittens in Rest’s garage. Rest’s family initially tried to raise them, but allergies made such a pet arrangement untenable. 

A cat lover, Collier was searching for kittens. She adopted two of the kittens, bottle feeding them starting at three days old. When Collier and Rest speak by zoom, Rest’s children Julia, nine, and Jonah, five, visit with the cats virtually.

As for their work, Collier and Rest are intrigued by the possibility of gathering additional pieces to answer questions about this virus.

“For me, the most intriguing question is how common our observations will turn out to be — do many Thraustochytrids have latent mirusviruses?” she explained.

by -
0 383
METRO photo

By Daniel Dunaief

Daniel Dunaief

We’ve come a long way from the “my dog ate my homework” days.

I mean, come on, let’s give our society the credit it’s due. We have taken the blame game, the finger pointing and the it-couldn’t-be-me-because-butter-wouldn’t-melt-in-my-mouth game to an entirely new stratosphere.

Gone are the days of simple, linear and mostly nonsensical excuses.

Let’s start in Washington, DC, which is the biggest clown show this side of the Atlantic and where the notion of a democracy gets battle tested nearly every day

Who is responsible for the national debt? That, of course, depends on whom you ask. The democrats point to former President Trump, while the republicans accuse President Biden and the Democrats.

Maybe those wily politicians are onto something. You see, if no one takes responsibility for anything and we can point fingers at the other side reflexively and without any effort to compromise and work together, we can live without consequence, create our own economics and come up with judgmental and schoolyard bully nicknames for the other side.

Brilliant! Blame someone else convincingly enough and not only do you not have to look in the mirror or come up with solutions, but you can also turn your entire reason for being into defeating the other side or, at the very least, enjoying their losses.

Look, I’m a Yankees fan. I know all about Schadenfreude. The next best thing to a Yankees victory, and it’s a close second, is a Red Sox loss.

But I digress. People have turned blaming others into a fine art. In sports, athletes and coaches deploy the modern blame game to excuse their losses or to step back from accepting responsibility or, perish the thought, to give the other team credit.

Like a zebra in the Serengeti to a hungry lion, referees in their striped uniforms in football games become convenient targets. They took away a victory by calling a game against us. Athletes and coaches can dig their verbal claws and teeth into those officials, who stole what would certainly have been a more favorable outcome.

How about school? It couldn’t possibly be the fault of our angelic children, who were busy watching these athletes on TV or on their phones the night before, for doing poorly on a test. It has to be the teacher’s fault. If teachers could only inspire their classes, our children would learn and excel. 

You know who I like to blame? I like to focus on tall people. Don’t get me wrong. Some of my best friends are tall. It’s just that, well, have you noticed that tall people get a lot of attention? Some of them are CEOs of big companies and make enormous salaries. They are also picked first in gym, which gives them the confidence to become successful.

While we’re affixing blame, let’s also shake our heads at gym class. Sure, it’s healthy to run around and have a few moments when we’re not listening to teachers who may or may not inspire us, but gym class can bruise egos and create a Darwinian world where height, which is kind of the fault of our parents and their parents and on and on, is an advantage.

Hey, I’m not whining. Okay, well, maybe I am, but it’s not me and it’s certainly not my fault. I blame society, commentators on TV, coaches, politicians, teachers, my parents, your parents, the parents of the kid who served as a bad role model for my kids, and maybe Adam, Eve and the snake for putting us in this position.

Oh, and you can be sure butter wouldn’t melt in my mouth. I have a dairy allergy, which, ironically, is the fault of my dairy farmer grandfather.

by -
0 1046
Christopher Vakoc with graduate student Junwei Shi. Photo by Gina Motisi/ CSHL.

By Daniel Dunaief

It is the type of miraculous conversion that doesn’t involve religion, and yet it may one day lead to the answer to passionate prayers from a group of people on a mission to help sick children.

Researchers in the lab of Professor Christopher Vakoc at Cold Spring Harbor Laboratory have been working tirelessly to understand the fundamental biology of Rhabdomyosarcoma, or RMS, which is a type of connective tissue cancer that afflicts between 400 and 500 people each year in the United States, with more than half receiving the diagnosis before they turn 10 years old.

As a part of her PhD research, Martyna Sroka searched for a way to convert the processes involved in this cancer into something benign.

Using a gene editing tool enhanced by another former member of Vakoc’s lab, Sroka disrupted a signal she had spent years trying to find in a protein called NF-Y, causing cancerous cells in a dish to differentiate into normal muscle cells, a conversion that offers future promise for treatment.

Sroka, who is now working as a scientist in a biotechnology company focused on the development of oncology drugs, described how RMS cells look small and round in a microscope. After disrupting this protein, the “differentiated cells become elongated and spindle-like, forming those long tubular structures,” she explained.

She often grew cells on plastic dishes and the differentiated RMS cells spanned the entire diameter of a 15 centimeter plate, providing a striking visual change that highlighted that conversion.

While this research represents an important step and has created considerable excitement in the scientific community and among families whose philanthropic and fundraising efforts made such a discovery possible, this finding is a long way from creating a new treatment.

Other research has indicated that disrupting NF-Y could harm normal cells. A potential therapeutic alteration in NF-Y could be transient and would likely include follow ups such as a surgical, radiation or biological approach to remove the converted RMS cells, Vakoc explained.

Nonetheless, the research, which was published in August in the prestigious Proceedings of the National Academy of Sciences, offers a potential roadmap for future discoveries.

“It was a long journey and being able to put the pieces of the puzzle together into a satisfying mechanism, which might have broader implications not only for our basic understanding of the biology of the disease but also for potential novel therapeutic approaches, was extremely exciting and rewarding,” said Sroka.

“It’s great to see so much excitement in the pediatric cancer field, and I am hoping that with time it will translate to much-needed novel therapeutic options for pediatric patients.”

The search

Cancer signals typically involve rewiring a cell’s genetic material, turning it into a factory that creates numerous, unchecked copies of itself.

Sroka and Vakoc were searching for the kind of signal that might force those cells down what they hope is a one-way differentiation path, turning those otherwise dangerous cells into more normal muscle cells that contract.

To find this NF-Y gene and the protein it creates, Sroka, who started working in Vakoc’s lab in the summer of 2017, screened over a 1,000 genes, which Vakoc described as a “heroic effort.”

Encouraged by this discovery and as eager to find new clinical solutions as the families who helped support his research, Vakoc recognizes he needs to strike a balance between trumpeting this development and managing expectations.

Interactions with the public, including families who have or are confronting this health threat, “comes with a lot of responsibility to make sure we’re being as clear as possible about what we’ve done and what have yet to do,” said Vakoc. “It’s going to be a long and uncertain road” to come up with new approaches to this cancer.

Funding families

Some of the families who provided the necessary funding for this work shared their appreciation for the commitment that Vakoc, Sroka and others have made.

“We are very excited about the newest paper [Vakoc and Sroka] published,” said Phil Renna, the Senior Director of Communications at CSHL and Director of the Christina Renna Foundation, which he and his wife Rene formed when their daughter Christina, who passed away at the age of 16, battled the disease. The Christina Renna Foundation has contributed $478,300 to Vakoc’s lab since 2007.

“In just a few short years, he has made a major leap forward. This lights the path of hope for us and our cause,” said Renna.

Renna explained that the lab has had numerous inquiries about this research. He and others recognize that the search for a cure or treatment involves “tough, grinding work” and that considerable basic research is necessary before the research can lead to clinical trials or new therapeutics.

Paul Paternoster, whose wife Michelle succumbed to the disease and who has raised funds, called Vakoc and Sroka “brilliant and incredibly hard working,” and suggested the exciting results “came as no surprise.”

He is “extremely pleased” with the discovery from the “standpoint of what it can lead to, and how quickly it was discovered.”

Paternoster, President of Selectrode Industries Inc., which manufactures welding products and has two factories in Pittsburgh, suggested that this strategy can have implications for other soft tissue sarcomas as well.

The next steps

To build on the discoveries Sroka made in his lab, Vakoc plans to continue to use a technique Junwei Shi, another former member of his lab, developed after he left CSHL and joined the University of Pennsylvania, where he is now a tenured professor.

Shi, whom Vakoc called a “legend” at CSHL for honing the gene editing technique called CRISPR for just this kind of study, is also a co author in this paper.

In future research, Vakoc’s lab plans to take the screens Sroka used to find NF-Y to search to the entire human genome.

“That’s how the family tree of science operates,” said Vakoc. Shi “made a big discovery of CRISPR and has since continued to create new technology and that he is now sharing back” with his lab and applying it to RMS. Additionally, Vakoc plans to expand the testing of this cellular conversion from plastic dishes to animal models

Shi, who worked in Vakoc’s lab from 2009 to 2016 while he earned his PhD at Stony Brook University, expressed satisfaction that his work is paying dividends for Vakoc and others.

“It just feels great that [Vakoc] is still using a tool that I developed,” said Shi in an interview. Many scientists in the field are using it, he added.

For Shi, who was born and raised in southern China, working at Cold Spring Harbor Laboratory fulfilled a lifelong dream.

He recalled how he retrieved data one Saturday morning that indicated an interesting pattern that might reveal the power of a new methodology to improve CRISPR screening.

When Vakoc came to the lab that morning, Shi shared the data, which was a “whole turning point,” Shi said. 

Shi said he appreciates how CSHL has been “a home for me,” where he learned modern molecular biology and genetics.

When he encounters a problem in his lab, he often thinks about how Vakoc would approach it. Similarly, Vakoc suggested he also reflects on how his mentor Gerd Blobel, who is a co-author on the recent paper and is at the Children’s Hospital of Philadelphia, would respond to challenges.

As for the family members of those eager to support Vakoc, these kinds of scientific advances offer hope.

When he started this journey, Renna suggested he would feel satisfied if researchers developed a cure in his lifetime. This paper is the “next step in a marathon, but it makes us very excited,” he said.

To share the encouraging results from Vakoc’s lab with his daughter, Renna tacked up the PNAS paper to the wall in Christina’s bedroom.

 

by -
0 457
METRO photo

By Daniel Dunaief

Daniel Dunaief

We are on the precipice of a few social evenings. As such, I have prepared the internal and external dialog of one such potential interaction. Yes, some of it reflects my performance in previous gatherings, while other elements are exaggerated versions of what may happen. And away we go:

“Hi Pat, it’s nice to meet you. I’m Dan.”

“Good to meet you, too, Dan.”

Ow, did you have to squeeze my hand that hard? Were you trying to prove something? I get it. You’re bigger and stronger than I am. You probably lift weights and stare at yourself in the mirror at the gym while you listen to Annie’s “Tomorrow.” No, I know you don’t listen to Annie. At least, not in public..

Not that you asked, but I like to sweat in the gym, too. I use the elliptical machine, the bike and the treadmill. 

“So, did Maria tell you about me?”

Wait, who’s Maria? Oh, right, your wife, the woman standing next to you. She’s the reason we’re here. Our wives worked together a few years ago and now the four of us are going out to dinner.

Pat is talking about how great he is at bowling.

He wants me to smile, so I’m smiling, but I’m not sure what he said. Maybe it was self deprecating? Nope, doesn’t seem likely. He’s talking about how much his average has gone up since he joined the Thursday night league.

“Good for you,” I say.

He nods appreciatively. Whew! I said the right thing. Go me! 

Oh, cool, now he’s talking about how great his son is at tennis. I’m picturing myself scuba diving. I’m looking at him, but I’m imaging fish around me, the warm water, and the bubbles that expand as they head to the surface. Nice! Life is good down here. Oh, wait, he just touched my shoulder. He wants me to say something. Staring into space isn’t enough.

“You know what I’m saying?” he asked.

I’m sorry, no. I don’t know, but I’m going to nod and hope that’s enough. Nope, clearly not.

“Tell me more about your son,” I say.

That’s enough. He’s off to the races with another story about some incredible app his son is working on that already has over 1,000 subscribers. My wife seems to be enjoying Maria’s company. Wait, no, she wrinkled her eyes subtly at me. Uh oh! She knows I’m not paying attention to John. No, that’s not his name. It begins with a P. No, hold on. I’ll get it. It’s Paul.

“So, Dan,” she says, “did Pat tell you about their plans to go to Alaska this summer?”

Pat! Duh. How easy was that? I would have gotten it eventually. No, I wouldn’t. Who am I kidding? 

I’m going to focus closely on his story. He’s talking about how much he enjoys vacations. I like vacations.

“Alaska was pretty amazing,” I say, hoping I shared the right sentiment. “We saw whales, drove a dog sled, and ate fresh fish.”

He’s always wanted to go to Alaska. He can’t wait to see the wide open terrain. He wonders whether it’ll be the same 500 years from now.

Assuming the Earth is still here and is habitable, what will humans be talking about and thinking about in 500 years? Will a potentially longer life span mean that future humans will be more patient? Will they think about what our life was like today? They’re as likely to think about us as we are to think about the people who shared the world of 1523.

The evening is almost over. We pay the check and talk about how wonderful it is to to go out together.

“Yes, we should do this again some time,” I say as we head towards the car. Maria and my wife give each other a professional hug – not too long and not too close – while Pat and I share a manly handshake. Pat seems to appreciate the firmer grip.

“Something wrong with your hand?” my wife asks as we walk towards the car.

“Nope, all good,” I say, as I try to bring the circulation back to my fingers.

by -
0 726
A Jamaican fruit bat, one of two bat species Scheben studied as a part of his comparative genomic work. Photo by Brock & Sherri Fenton

By Daniel Dunaief

Popular in late October as Halloween props and the answer to trivia questions about the only flying mammals, bats may also provide clues about something far more significant.

Despite their long lives and a lifestyle that includes living in close social groups, bats tend to be resistant to viruses and cancer, which is a disease that can and does affect other mammals with a longer life span.

Armin Scheben

In recent work published in the journal Genome Biology and Evolution, scientists including postdoctoral researcher at Cold Spring Harbor Laboratory and first author Armin Scheben, CSHL Professor and Chair of the Simons Center for Quantitative Biology Adam Siepel, and CSHL Professor W. Richard McCombie explored the genetics of the Jamaican fruit bat and the Mesoamerican mustached bat.

By comparing the complete genomes for these bats and 13 others to other mammals, including mice, dogs, horses, pigs and humans, these scientists discovered key differences in several genes.

The lower copy number of interferon alpha and higher number of interferon omega, which are inflammatory protein-coding genes, may explain a bat’s resistance to viruses. As for cancer, they discovered that bat genomes have six DNA repair and 33 tumor suppressor genes that show signs of genetic changes.

These differences offer potential future targets for research and, down the road, therapeutic work.

“In the case of bats, we were really interested in the immune system and cancer resistance traits,” said Scheben. “We lined up those genomes with other mammals that didn’t have these traits” to compare them.

Scheben described the work as a “jumping off point for experimental validation that can test whether what we think is true: that having more omega than alpha will develop a more potent anti-viral response.”

Follow up studies

This study provides valuable potential targets that could help explain a bat’s immunological superpowers that will require further studies.

“This work gives us strong hints as to which genes are involved, but fully understanding the molecular biology will require more work” explained Siepel.

In Siepel’s lab, where Scheben has been conducting his postdoctoral research since 2019, he is using human cell lines to see whether adding genetic bat elements makes them more effective in fighting off viral infections and cancer. He plans to do more of this work with mice, testing whether these bat variants help convey the same advantages in live mice.

Armin Scheben won the German Academic International Network Science Slam competition with his presentation on bat genomics.

Siepel and Scheben have discussed improving the comparative analysis by collecting information across bats and other mammals of tissue-specific gene expression and epigenetic marks which would help reveal changes not only in the content of DNA, but also in how genes are being turned on and off in different cell types and tissues. That could allow them to focus more directly on key genes to test in mice or other systems.

Scheben has been collaborating with CSHL Professor Alea Mills, whose lab has “excellent capabilities for doing genome editing in mice,” Scheben said.

Scheben’s PhD thesis advisor at the University of Western Australia, Dave Edwards described his former lab member’s work as “exciting.”

Edwards, who is Director of the UWA Centre for Applied Bioinformatics in the School of Biological Sciences, suggested that Scheben stood out for his “ability to strike up successful collaborations” as well as his willingness to mentor other trainees.

Other possible explanations

While these genetic differences could reveal a molecular biological mechanism that explains the bat’s enviable ability to stave off infections and cancer, researchers have proposed other ways the bat might have developed these virus and cancer fighting assets.

When a bat flies, it raises its body temperature. Viruses likely prefer a normal body temperature to operate optimally. 

Bats are “getting fevers without getting infections,” Scheben said.

Additionally, flight increases the creation of reactive oxygen species, which the bat needs to control on an ongoing basis.

At the same time, bats produce fewer inflammatory cytokines, which helps prevent them from having a runaway immune reaction. Some researchers have hypothesized that bats clear reactive oxygen species more effectively than humans.

A ‘eureka’ moment

The process of puzzling together all the pieces of DNA into individual chromosomes took considerable time and effort.

A Mesoamerican mustached bat, one of two bat species Scheben studied as a part of his comparative genomic work. Photo by Brock & Sherri Fenton

Scheben spent over 280,000 CPU hours chewing through thousands of genes in dozens of species on the CSHL supercomputer called Elzar, named for the chef from the cartoon “Futurama.” Such an effort would have taken eight years on a modern day personal computer.

During this effort, Scheben saw this “stark effect,” he said. “We had known that bats had lost some interferon alpha. What astounded me was that some bats had lost all alpha” while they had also raised interferon omega. That was the moment when he realized he found something novel and bat specific.

Scheben recognized that this finding could be one of many that lead to a better understanding of the processes that lead to cancer.

“We know that it’s unlikely that a single set of genes or a small set of genes such as we identified can fully explain the diversity of outcomes when it comes to a complex disease like cancer,” said Scheben.

A long journey

A resident of Northport, Scheben grew up in Frankfurt, Germany. He moved to London for several years, which explains his use of words like “chuffed” to describe the excitement he felt when he received a postdoctoral research offer at Cold Spring Harbor Laboratory.

When he was young, Scheben was interested in science despite the fact that classes were challenging for him.

“I was pretty poor in math and biology, but I liked doing it,” he said.

Outside of work, Scheben enjoys baking dense, whole wheat German-style bread, which he consumes with cheese or with apple, pear and nuts, and also hiking.

As for his work, which includes collaborating with CSHL Professor Rob Martienssen to study the genomes of plants like maize that make them resilient amid challenging environmental conditions, Scheben suggested it was the “best time to be alive and be a biologist” because of the combination of new data and the computational ability to study and analyze it.

Scheben recognized that graduate students in the future may scoff at this study, as they might be able to compare a wider range of mammalian genomes in a shorter amount of time.

Such a study could include mammals like naked mole rats, whales and elephants, which also have low cancer incidence and long lifespans.

by -
0 337
METRO photo

By Daniel Dunaief

Daniel Dunaief

My wife and I used to say “the recording is always on.”

It was our code words to each other to be careful about what we said and did in front of our children, particularly when, as many parents know, we might not want our children to act or speak in the same way we might be tempted to in the moment.

Our children have an incredible ability to monitor everything we do, even when they don’t appear to be paying any attention to us. Sometimes, they actively choose the opposite because our choices annoyed or frustrated them.

If, as many of us say and believe, we want our children to be better than we are, we wish them well, wait and watch, hoping their happiness, success and achievements far exceed our own.

Perhaps such reaction formation is what brings grandparents and grandchildren together, causing various characteristics to skip a generation, as two opposites create the same.

Aside from things like weekly routines, an emphasis (or not) on achievements like community service, or performance in sports or music, parents recognize that we are role models.

In the movie “42” about trailblazer Jackie Robinson, the first African-American man to play in Major League Baseball, a father shouts racial epithets at Robinson, leading his conflicted son to ponder how to behave. The son echoes what his father shouts.

In that moment, Peewee Reese puts his arm around Robinson, offering his public support and quieting the hostile crowd. Reese even suggests, as a nod to the realities of today, that “Maybe tomorrow we’ll all wear number 42. That way they won’t tell us apart.”

Films are great, but we don’t live in a world where supportive music and smiling heroes remind us who we are or how we should act.

It’s up to us to decide how to be better for ourselves and for our children.

A friend recently shared a story about his daughter. A college student, she was working at an ice cream store during a fall break. A few customers came in and a man in the group asked her where she attended college.

When she told him, the man suggested that there were Muslims who attended that college and it would be easy enough to take a few of them behind the shed and get rid of them.

The man who made a joke about murder at a time of violent conflict in the Middle East and ongoing and hostile disagreements among Americans probably wasn’t thinking about his children, about my friend’s daughter, or anyone else.

Maybe he was repeating the words his father or mother said at the dinner table, after an evening of drinking or within minutes of leaving a house of worship.

Is that the person he wants to be? Is that what he would encourage his own children to believe, that people who practice other religions or have other beliefs are somehow such enemies that it’s okay to make such a comment?

We have to be better than that. Maybe the guy didn’t mean it, but even saying it suggests that he not only thought it, but that he also likely shared that idea in some context in front of his children.

Killing and hatred won’t end if we don’t hold ourselves accountable for our actions and words.

We identify ourselves in particular ways, by such factors as nationality, religion, race, among many other labels.

Those identifiers, many of which we didn’t choose but are an accident of our birth, mean that others around us are on the outside, associating with a different group.

We owe it to our children to imagine and create a better world. That starts by serving as role models and not as reflexive perpetuators of anger, hatred, or prejudice towards those we consider others.

With the world echoing the conditions from the 20th century, we should speak and act in ways that bring people together and that would make us proud if and when we heard our children making those same, or perhaps better, remarks.

Prev1...456...70Next Page 5 of 70
TBR News Media is your local news and entertainment website.
We provide you with the latest breaking news and information for your community.
Contact us: [email protected]

Most Viewed

©