Science & Technology

By Elof Axel Carlson

Elof Axel Carlson

The first time I heard DNA enter popular culture was hearing a record played by my son Anders. I heard the refrain, “Hey hey, hey hey! It’s DNA that made me that way.” Anders told me it was from a song called “Sheer Heart Attack” by the rock band Queen (1977).  

Since then that idea has spread from teenage rock fans to the public sphere, and in its modified form, I hear “It’s in my DNA” when a person feels passionately about an idea. Metaphors are part of how we speak but they are not always scientifically accurate. Before the era of DNA (that began with the publishing of the double helix model of DNA in 1953 by James Watson and Francis Crick), a different set of metaphors were in use going back to antiquity. 

Intense belief or fixed behaviors have been attributed to the intestines (I feel it in my gut), to the heart (I offer my heart-felt thanks), to the skeletal system (I feel it to the marrow of my bones), to the blood (royalty are blue bloods and a psychopath’s behavior reflects bad blood) and to the nervous system (argumentative personalities are called “hot headed”). 

Sumerians studied the shape of animal guts and livers to predict the future (haruspicy). Until the Renaissance the brain was thought to be the place where blood is cooled (hence the hot-headed belief). Thoreau was described by one contemporary as sucking the marrow out of life; and blood was considered the vital fluid of life. In the Renaissance the first human blood transfusions were given to provide youthful vigor by old men who believed in rejuvenation.  

When people say, “It’s in my DNA” for a behavior, they are conveying a deeply held belief that it is part of their personality as far back as they can remember or that it is innate. But the evidence for innate human social behaviors is often lacking. There are single gene effects of the nervous system that are well documented such as Huntington’s disease, which leads to dementia and paralysis with an onset usually in middle age. 

There are also family histories of psychosis and learning difficulties. The fragile X syndrome is one such well-documented condition that leads to low intelligence. But human social traits have lots of inputs from parents, siblings, playmates, neighborhoods, regional culture, ethnicity and national identity.  

Children growing up in poverty have different expectations than children whose parents are well off and send them to elite schools. Each generation uses, as best as it can, what it knows. Our knowledge of many important aspects of life and behavior is incomplete. Hence, we keep modifying our interpretations of how life works.  

Much of what is called evolutionary psychology or genetic determinism will be modified or abandoned in years to come as we learn how our genes use memories and other acquired knowledge to shape our personalities. For many cellular processes we know the flow of information from DNA (genes) to cell organelles to cellular function to tissue formation and to organ formation.  

That detailed interpretation of human behavior is not possible now for social traits. I would love to say, “It’s in my DNA” to write these Life Line columns, but my conscience would remind me that it is based on Freudian “wish fulfillment” and not careful experimentation down to the molecular level.

Elof Axel Carlson is a distinguished teaching professor emeritus in the Department of Biochemistry and Cell Biology at Stony Brook University.

Weisen Shen in front of a twin-otter airplane in the Antarctic during the 2017-18 season. Photo by Zhengyang Zhou

By Daniel Dunaief

Ever sit alone in a house and hear noises you can’t explain? Was that the wind, the house settling (whatever that means) or the cat swatting at the string hanging from the blinds?

Those sounds, which are sometimes inexplicable and are called ambient noise, are often hard to trace, even if we walk around the house and listen outside every room.

Weisen Shen
Photo by John Griffin

For Weisen Shen, an assistant professor in the Department of Geosciences at Stony Brook University, ambient noises deep below the Antarctic continent and elsewhere can be and often are clues that unlock mysteries hidden miles below the frozen surface.

A geoscientist who uses computer programs in his research, Shen would like to study the temperature well below the surface. He developed an in-house code to understand and interpret seismic data.

The speed at which Earth rumbling passes from one area to another can indicate the relative temperature of an area. Seismic activity moves more slowly through warmer rocks and moves more rapidly through colder crust, which has a higher rigidity. According to Shen, these temperature readings can help provide a clearer understanding of how much heat is traveling through the surface of the solid Earth into the ice sheet.

Shen traveled to the Ross Ice Shelf in the 2015-16 season and ventured to the South Pole in the 2017-18 season. He is currently seeking funding to go back to the Antartica. Earlier this year, he published an article in the journal Geology in which he found evidence that the lithosphere beneath the Transantarctic Mountains is thinner than expected.

Shen pointed out that seismic properties aren’t just related to temperature: They can help determine the density of the material, the composition and the existence of fluid such as water. He looks for surface geology and other types of geophysical data to detect what is the dominant reason for seismic structure anomalies. He also uses properties other than speed, such as seismic attenuation and amplitude ratios, in his analysis.

This kind of information can also provide an idea of the underlying support for mountain ranges, which get built up and collapse through a lithographic cycling.

As for ambient noises, Shen explained that they can come from ocean fluctuations caused by a hurricane, from human activities or, most commonly, from the bottom of the ocean, where the dynamic ocean wave constantly pushes against the bottom of the earth. By processing the noises in a certain way, he can extract information about the materials through which the noise traveled.

Shen published an article in the Journal of Geophysical Research in which he discussed a noise source in Kyushu Island in the Japanese archipelago. “The noise is so subtle that people’s ears will never catch it,” he said. “By deploying these very accurate seismic sensors, we will be able to monitor and study all the sources of those noises, not just the earthquakes.”

Studying these lower volume, less violent noises is especially helpful in places like Antarctica, which is, Shen said, a “quiet continent,” without a lot of strong seismic activity. He also uses the images of earthquakes that occur elsewhere, which travel less violently and dramatically through Antarctica.

Shen decided to study Antarctica after he earned his doctorate at the University of Colorado at Boulder. “I have this ambition to get to all the continents,” he said. In graduate school he told himself, “If you ever want to get that work done, you have to crack this continent.”

During his postdoctoral work, Shen moved to St. Louis, where he worked at Washington University in the laboratory of Doug Wiens, professor of Earth and planetary sciences.

In addition to conducting research in Antarctica, Shen collaborated with Chen Cai, a graduate student in Wiens’ lab. Together with other members of the Washington University team, they used seismic data in the Mariana Trench to show that about three to four times more water than previously estimated traveled beneath the tectonic plates into the Earth’s interior.

That much water rushing further into the Earth, however, is somehow offset by water returning to the oceans, as ocean levels haven’t changed dramatically through this part of the water cycle process.

“People’s estimates for the water coming out is probably out of balance,” Wiens said. “We can’t through millions of years bring lots of water through the interior. The oceans would get lower. There’s no evidence” to support that, which means that “an upward revision of the amount of water coming out of the Earth” is necessary. That water could be coming out through volcanoes or perhaps through the crust or gas funnels beneath the seafloor, he suggested.

Wiens praised all the researchers involved in the study, including Shen, whom he said was “very important” and “wrote a lot of the software we used to produce the final images.”

A resident of Queens, Shen lives with his wife Jiayi Xie, who works as a data scientist at Xaxis, a subcompany of the global media firm GroupM. The couple has an infant son, Luke.

Shen grew up in the southwestern part of China. When he was younger, he was generally interested in science, although his particular passion for geoscience started when he was in college at the University of Science and Technology of China, USTC, in Hefei, Anhui, China.

The assistant professor, who teaches a geophysics class at Stony Brook University, currently has two graduate students in his lab. He said he appreciates the support Stony Brook provides for young faculty.

As for his work, Shen is excited to contribute to the field, where he enjoys the opportunity and camaraderie that comes from exploring parts of Earth that are relatively inaccessible. He feels his detailed studies can help change people’s understanding of the planet.

Photo by Ela Elyada

By Daniel Dunaief

What if, instead of defeating or removing enemy soldiers from the battlefield, a leader could convince them to join the fight, sending them back out to defeat the side they previously supported? That’s the question Giulia Biffi, a postdoctoral researcher at Cold Spring Harbor Laboratory, is asking about a particular type of cells, called fibroblasts, that are involved in pancreatic cancer.

Fibroblasts activated by cancer cells secrete a matrix that surrounds cancer cells and makes up about 90 percent of pancreatic tumors.

Giulia Biffi. Photo by ©Gina Motisi, 2018/CSHL

Responding to a molecule called IL-1, an inflammatory potential tumor-promoting fibroblast may enhance the opportunity for cancer to grow and spread. Another type of fibroblast responds to TGF-beta, which potentially enables them to restrain tumors.

Researchers had suggested that the inflammatory fibroblasts are tumor promoting, while the myofibroblasts are tumor defeating, although at this point, that still hasn’t been confirmed experimentally.

Researchers knew TGF-beta was important in biology, but they didn’t know that it was involved in preventing the activation of an inflammatory tumor-promoting version.

Biffi, however, recently found that IL-1 promotes the formation of inflammatory fibroblasts. She believes these fibroblast promote tumor growth and create an immunosuppressive environment.

In an article published in the journal Cancer Discovery, Biffi showed that it’s “not only possible to delete the population, but it’s also possible to convert [the fibroblasts] into the other type, which could be more beneficial than just getting rid of the tumor-promoting cells,” she said.

Biffi works in Director Dave Tuveson’s CSHL Cancer Center laboratory, which is approaching pancreatic cancer from numerous perspectives.

Her doctoral adviser, Sir Shankar Balasubramanian, the Herchel Smith Professor of Medicinal Chemistry at the University of Cambridge, suggested that the work she did in Tuveson’s lab is an extension of her successful research in England.

“It is evident that [Biffi] is continuing to make penetrating and important advances with a deep and sophisticated approach to research,” Balasubramanian explained in an email. “She is without a doubt a scientist to watch out for in the future.”

To be sure, at this stage, Biffi has performed her studies on a mouse model of the disease and she and others studying fibroblasts and the tumor microenvironment that dictates specific molecular pathways have considerable work to do to extend this research to human treatment.

She doesn’t have similar information from human patients, but the mouse models show that targeting some subsets of fibroblasts impairs cancer growth.

“One of the goals we have is trying to be able to better classify the stroma from pancreatic cancer in humans,” Biffi said. The stroma is mixed in with the cancer cells, all around and in between clusters of cells.

The results with mice, however, suggest that approaching cancer by understanding the molecular signals from fibroblasts could offer a promising additional resource to a future treatment. In a 10-day study of mice using a specific inhibitor involved in the pathway of inflammatory fibroblasts, Biffi saw a reduction in tumor growth.

If Biffi can figure out a way to affect the signals produced by fibroblasts, she might be able to make the stroma and the cancer cells more accessible to drugs. One potential reason other drugs failed in mouse models is that there’s increased collagen, which is a barrier to drug delivery. Drugs that might have failed in earlier clinical efforts could be reevaluated in combination with other treatments, Biffi suggested, adding if scientists can manage to target the inflammatory path, they might mitigate some of this effect.

A native of Bergamo, Italy, which is near Milan, Biffi earned her doctorate at the Cancer Research UK Cambridge Institute. Biffi lives on a Cold Spring Harbor property which is five minutes from the lab.

When she was young, Biffi wanted to be a vet. In high school, she was fascinated by the study of animal behavior and considered Dian Fossey from “Gorillas in the Mist” an inspiration. When she’s not working in the lab, she enjoys the opportunity to see Broadway shows and to hike around a trail on the Cold Spring Harbor campus.

Biffi started working on fibroblasts three years ago in Tuveson’s lab. “I really wanted to understand how fibroblasts become one population or the other when they were starting from the same cell type,” she said. “If they have different functions, I wanted to target them selectively to understand their role in pancreatic cancer to see if one might have a tumor restraining role.”

A postdoctoral researcher for over four years, Biffi is starting to look for the next step in her career and hopes to have her own lab by the end of 2019 or the beginning of 2020.

When she was transitioning from her doctoral to a postdoctoral job, she was looking for someone who shared her idealistic view about curing cancer. Several other researchers in Cambridge suggested that she’d find a welcome research setting in Tuveson’s lab. Tuveson was “popular” among principal investigators in her institute, Biffi said. “I wanted to work on a hard cancer to treat and I wanted to work with [Tuveson].”

Biffi hopes that targeting the inflammatory pro-tumorigenic fibroblasts and reprogramming them to the potentially tumor-restraining population may become a part of a pancreatic cancer treatment.

She remains optimistic that she and others will make a difference. “This can be a frustrating job,” she said. “If you didn’t have hope you can change things, you wouldn’t do it. “I’m optimistic.”

Biffi points to the hard work that led to treatments for the flu and for AIDS. “Years back, both diseases were lethal and now therapeutic advances made them manageable,” she explained in an email. “That is where I want to go with pancreatic cancer.”

Andrew Schwartz. Photo courtesy of Stony Brook University

By Daniel Dunaief

In the era of social media, people reveal a great deal about themselves, from the food they eat, to the people they see on a subway, to the places they’ve visited. Through their own postings, however, people can also share elements of their mental health.

In a recent study published in the journal Proceedings of the National Academy of Sciences, Andrew Schwartz, an assistant professor in the Department of Computer Science at Stony Brook University, teamed up with scientists at the University of Pennsylvania to describe how the words volunteers wrote in Facebook postings helped provide a preclinical indication of depression prior to a documentation of the diagnosis in the medical record.

Using his background in computational linguistics and computational psychology, Schwartz helped analyze the frequency of particular words and the specific word choices to link any potential indicators from these posts with later diagnoses of depression.

Combining an analysis of the small cues could provide some leading indicators for future diagnoses.

“When we put [the cues] all together, we get predictions slightly better than standard screening questionnaires,” Schwartz explained in an email. “We suggest language on Facebook is not only predictive, but predictive at a level that bears clinical consideration as a potential screening tool.”

Specifically, the researchers found that posts that used words like “feelings” and “tears” or the use of more first-person pronounces like “I” and “me,” along with descriptions of hostility and loneliness, served as potential indicators of depression.

By studying posts from consenting adults who shared their Facebook statuses and electronic medical record information, the scientists used machine learning in a secure data environment to identify those with a future diagnosis of depression.

The population involved in this study was restricted to the Philadelphia urban population, which is the location of the World Well-Being Project. When he was at the University of Pennsylvania prior to joining Stony Brook, Schwartz joined a group of other scientists to form the WWBP.

While people of a wide range of mental health status use the words “I” and “me” when posting anecdotes about their lives or sharing personal responses to events, the use of these words has potential clinical value when people use them more than average.

That alone, however, is predictive, but not enough to be meaningful. It suggests the person has a small percentage increase in being depressed but not enough to worry about on its own. Combining all the cues, the likelihood increases for having depression.

Schwartz acknowledged that some of the terms that contribute to these diagnoses are logical. Words like “crying,” for example, are also predictive of being depressed, he said.

The process of tracking the frequency and use of specific words to link to depression through Facebook posts bears some overlap with the guide psychiatrists and psychologists use when they’re assessing their patients.

The “Diagnostic and Statistical Manual of Mental Disorders” typically lays out a list of symptoms associated with conditions such as schizophrenia, bipolar disorder or depression, just to name a few.

“The analogy to the DSM and how it works that way is kind of similar to how these algorithms will work,” Schwartz said. “We look at signals across a wide spectrum of features. The output of the algorithm is a probability that someone is depressed.”

The linguistic analysis is based on quantified evidence rather than subjective judgments. That doesn’t make it better than an evaluation by mental health professional. The algorithm would need more development to reach the accuracy of a trained psychologist to assess symptoms through a structured interview, Schwartz explained.

At this point, using such an algorithm to diagnose mental health better than trained professionals is a “long shot” and not possible with today’s techniques, Schwartz added.

Schwartz considers himself part computer scientist, part computational psychologist. He is focused on the intersection of algorithms that analyze language and apply psychology to that approach.

A person who is in therapy might offer an update through his or her writing on a monthly basis that could then offer a probability score about a depression diagnosis.

Linguistic tools might help determine the best course of treatment for people who have depression as well. In consultation with their clinician, people with depression have choices, including types of medications they can take.

While they don’t have the data for it yet, Schwartz said he hopes an algorithmic assessment of linguistic cues ahead of time may guide decisions about the most effective treatment.

Schwartz, who has been at SBU for over three years, cautions people against making their own mental health judgments based on an impromptu algorithm. “I’ve had some questions about trying to diagnose friends by their posts on social media,” he said. “I wouldn’t advocate that. Even someone like me, who has studied how words relate to mental health, has a hard time” coming up with a valid analysis, he said.

A resident of Sound Beach, Schwartz lives with his wife Becky, who is a music instructor at Laurel Hill Middle School in Setauket, and their pre-school-aged son. A trombone player and past  member of a drum and bugle corps, he met his wife through college band.

Schwartz grew up in Orlando, where he met numerous Long Islanders who had moved to the area after they retired. When he was younger, he used to read magazines that had 50 lines of computer code at the back of them that created computer games.

He started out by tweaking the code on his own, which drove him toward programming and computers.

As for his recent work, Schwartz suggested that the analysis is “often misunderstood when people first hear about these techniques. It’s not just people announcing to the world that they have a condition. It’s a combination of other signals, none of which, by themselves, are predictive.”

Sam Aronson. Photo courtesy of BNL

By Daniel Dunaief

Sam Aronson, the retired head of Brookhaven National Laboratory, has set his sights on a new project far from Long Island.

Teaming up with Acacia Leakey, the project management and engineering consultant of a company called SOSAED and a member of the famed family that has made seminal discoveries about human evolution in Kenya, Aronson would like to stimulate the growth of businesses through the use of solar power that provides products and services.

“This [part of Africa] is an area where there’s really little infrastructure,” Aronson said. “We’re looking to help people get up on the economic pyramid.”

The people Aronson and Leakey would like to help are representative of the one billion people without access to electric power. Two-thirds of them live in sub-Saharan Africa.

Through SOSAED — which stands for Sustainable Off-grid Solutions for African Economic Development — Aronson and Leakey are working with the Turkana Basin Institute of northern Kenya, Stony Brook University, Strathmore University in Nairobi and other Kenyan educational institutions and businesses to integrate business creation in off-grid areas into the larger Kenyan economic ecosystem.

The group would like to create a business model, using local workers and managers, for a range of companies, Leakey explained.

SOSAED plans to start with a small-scale solar-powered clothing production business, which would create affordable clothing for the heat, including skirts, shirts and shorts. SOSAED expects to build this plant adjacent to the TBI research facility.

Ideally, the manufacturer will make the clothing from local material. The clothing business is a pilot project to see whether the model can work for other types of projects in other areas. The Turkana Basin Institute will provide some of the infrastructure, while SOSAED will acquire the equipment and the raw materials and training to do the work.

SOSAED hopes the project will become “self-sustaining when it’s up and running,” Aronson said. “To be sustainable, it has to be the work of local people.” He hopes what will differentiate this effort from other groups’ attempts to build economic development is the commitment to maintenance by people living and working in the area.

“To an extent, the suitability of technology is rarely rigorously considered when humanitarian or generic development projects are implemented,” Leakey explained in an email. “Not only are the skills required for maintenance an important consideration, the availability of spare parts and the motivation and ability to pay for these are also important.”

Developing a system that includes upkeep by people living and working in the area could “make a project move ahead on its own steam,” Aronson said. The area has limited infrastructure, although some of that is changing as new roads and government-funded water projects begin.

Leakey suggested that a long-term project would need extensive participation of the users in every step of the development and implementation. “The project will likely look very different once complete to how we envisage it now, and part of our success (if it comes) will lie in working in a way which allows a great degree of flexibility as it is unlikely we’ll design the ‘right’ system the first time around,” she explained in an email.

In areas with mature systems, Leakey suggested that some organizations had difficulty changing direction, retrofitting existing systems or adapting new technology. New York, she explained, is struggling to adopt sustainable technologies to the extent that it could. “Legislative and physical infrastructure imposes unfortunate roadblocks in the way of clean technologies,” she wrote in an email. “We’re fortunate that with electricity provision we have a fairly blank slate” in Kenya and that the “Kenya government also recognizes the value of off-grid initiatives.”

Leakey appreciates the support TBI played in helping to create SOSAED and is grateful for the ongoing assistance. Through Stony Brook University, SOSAED is beginning to engage business students on economic questions. In the future, the group may also work with engineering students on technological challenges.

“Research may include developing new productive uses of solar power, optimizing the existing system and using the site to rigorously test technologies developed at Stony Brook,” she explained.

Aronson’s initial interest in this project came from his technological connection to Brookhaven National Laboratory, where he retired as the director in 2015. He has been eager to bring new technology to a population he is confident they can help in a “way that makes sense to them and addresses their needs.”

With the support of the Turkana Basin Institute and Stony Brook, Aronson hopes to have a functioning solar hub and factory near TBI that serves a few surrounding villages within the next 18 months. “That’s a very ambitious goal,” he acknowledged. “We’re working in an environment that, because of the history and development, people you’re trying to serve are somewhat skeptical that you’re serious and that you have the staying power to make something that looks like what you’re talking about work.” 

While Aronson and Leakey are continuing to make connections in Kenya with government officials and residents interested in starting businesses, they are searching for ways to make this effort financially viable.

SOSAED is raising money through philanthropic grants and foundations to get the project going. Eventually, they hope to approach venture capital firms who are patient and prepared to invest for the longer term in a number of projects.

After they have an initial example, they will approach other financial backers with more than just a good idea, but with a model they hope will work in other locations.

Aronson lauded the effort and knowledge of Leakey. “We wouldn’t be making much progress right now for a variety of reasons in Kenya if [Leakey] hadn’t come on board,” Aronson said. “I value in the extreme her ability to get the work done.”

SOSAID would like to submit proposals to funding sources that can drive this concept forward.

If this effort takes root, Aronson believes there is a “tremendous market out there.” That would mean this would “become a much bigger organization.”

Gábor Balázsi. Photo by Dmitry Nevozhay

By Daniel Dunaief

An especially hot July day can send hordes of people to Long Island beaches. A cooler July temperature, however, might encourage people to shop at a mall, catch a movie or stay at home and clean out clutter.

Similarly, genes in yeast respond to changes in temperature.

Gábor Balázsi, the Henry Laufer associate professor of physical and quantitative biology at Stony Brook University, recently published research in the Proceedings of the National Academy of Sciences on the effect of temperature changes on yeast genes.

“We are looking at single cells and at genetic systems and we can dissect and understand gene by gene with a high level of detail,” said Balázsi, who used synthetic genetic systems to allow him to dissect and understand how temperature affects these genes.

Understanding the basic science of how genes in individual cells respond to temperature differences could have broad applications. In agriculture, farmers might need to know how genes or gene circuits that provide resistance to a pathogen or drought tolerance react when the temperature rises or falls.

Similarly, researchers using genetically designed biological solutions to environmental problems, like cleanups at toxic spills, would need to understand how a change in temperature can affect their systems.

Lingchong You, an associate professor of biomedical engineering at Duke University, believes the research is promising.

“Understanding how temperature will influence the dynamics of gene circuits is intrinsically interesting and could serve as a foundation for the future,” You said. Researchers “could potentially design gene circuits to program the cell such that the cell will somehow remember its experience with the fluctuating temperatures,” which could provide clues about the experience of the cell.

Balázsi suggested the goal of his work is to understand the robustness of human control over cells in nonstandard conditions.

While other researchers have explored the effects of gene expression for hundreds of genes at different temperatures, Balázsi looked more precisely at single genes and human-made synthetic gene circuits in individual cells. He discovered various effects by inserting a two-gene circuit into yeast.

At the whole-cell level when temperatures rise from 30°C to 38°C, some cells continued growing, albeit at a slower rate, while others stopped growing and started to consume their proteins.

For the second type of cells, changing temperatures can lead to cell death. If the temperature comes down to normal levels soon enough, however, researchers can rescue those cells.

“How this decision happens is a question that should be addressed in the future,” Balázsi said.

While the dilution of all proteins slows down, the chemical reactions in which they participate speed up at a higher temperature, much like children who become more active after receiving sugar at a birthday party.

At another level, certain individual molecules change their movement between conformations at a higher temperature. Proteins wiggle more between different folding conformations even if they don’t change composition. This affects their ability to bind DNA.

Balázsi said he is fortunate that he works through the Laufer Center for Physical and Quantitative Biology, which partly supported the work, where he was able to find a collaborator to do molecular dynamic simulations. Based on the pioneering experiments of postdoctoral fellow Daniel Charlebois, with help from undergraduate researcher Sylvia Marshall, the team collected data for abnormal behaviors of well-characterized synthetic gene circuits. They worked with Kevin Hauser, a former Stony Brook graduate research assistant, who explained how the altered conformational movements affected how the protein and cells behaved.

The way proteins fold and move between conformations determines what they do.

Gábor Balázsi with his daughter Julianna at West Meadow Beach
Photo from Gábor Balázsi

Taking his observations and experiments further, Balázsi found that proteins that were unbound to a small molecule didn’t experience a change in their conformation. When they were linked up, however, they demonstrated a new behavior when heated. This suggests that understanding the effects of temperature on these genetic systems requires an awareness of the proteins involved, as well as the state of their interaction with other molecules.

While Balázsi explored several ways temperature changes affect the yeast proteins, he acknowledged that other levels or forces might emerge that dictate the way these proteins change.

Additionally, temperature changes represent just one of many environmental factors that could control the way the genetic machinery of a cell changes. The pH, or acidity, of a system might also change a gene or group of genes.

A main overarching question remains as to how much basic chemical and physical changes combine with biological effects to give predictable, observable changes in the behaviors of genes and living cells.

Balázsi may test other cell types. So far, he’s only looked at yeast cells. He would also like to know the order in which the various levels of reactions — from the whole cell to the molecular level — occur.

He is interested in cancer research and possibly defense applications and would like to take a closer look at the way temperature or other environmental factors impact human disease processes and progression or think about their relevance for homeland security or biological solutions to renewable energy.

Balázsi recognizes that he and others in this field have numerous hurdles to overcome to find acceptable appreciation for the application of synthetic gene circuits.

“It’s not so simple to engineer these cells reliably,” he said. “Some roadblocks need to be eliminated to convince people it’s feasible and useful.”

Balázsi suggested that the field of virology might benefit from pursuing some of these research questions. Viruses move from the environment or even from other hosts into humans. Avian influenza, for example, can begin inside a bird and wind up affecting people. These viruses “might have different expression patterns in birds versus humans,” he said.

Ultimately, he added, this kind of scientific pursuit is “multipronged and the applications are numerous.”

Francis Alexander. Photo from BNL

By Daniel Dunaief

Now what? It’s a question that affects everyone from the quarterback who wins the Super Bowl — who often says something about visiting a Disney facility — to the student who earns a college degree, to the researcher who has published a paper sharing results with the scientific community.

For some, the path forward is akin to following footsteps in the snow, moving ever closer to a destination for which a path is clear. For others, particularly those developing new technology, looking to unlock mysteries, the path is more like trudging through unfamiliar terrain.

The technology at facilities like Brookhaven National Laboratory, which includes the powerful National Synchrotron Light Source II and the Center for Functional Nanomaterials, among others, enables scientists to see processes at incredibly fine scales.

While these sites offer the promise of providing a greater ability to address questions such as what causes some batteries to die sooner than others, they also cost considerable money to use, putting pressure on researchers to ask the most fruitful question or pursue research that has the greatest chance for success.

Francis Alexander. Photo from BNL

That’s where people like Francis Alexander, the deputy director of Brookhaven National Laboratory’s Computational Science Initiative, and his team at BNL can add considerable value. Alexander takes what researchers have discovered, couples it with other knowledge, and helps guide his fellow laboratory scientists to the next steps in their work — even if he, himself, isn’t conducting these experiments.

“Given our theoretical understanding of what’s going on, as imperfect as that may be, we take that understanding — the theory plus the experimental data — and determine what experiments we should do next,” Alexander said. “That will get us to our goal more quickly with limited resources.”

This approach offers a mutually reinforcing feedback loop between discoveries and interpretations of those discoveries, helping researchers appreciate what their results might show, while directing them toward the next best experiment.

The experiments, in turn, can either reinforce the theory or can challenge previous ideas or results, forcing theoreticians like Alexander to use that data to reconstruct models that take a wide range of information into account.

Alexander is hoping to begin a project in which he works on developing products with specific properties. He plans to apply his knowledge of theoretical physics to polymers that will separate or grow into different structures. “We want to grow a structure with a [particular] function” that has specific properties, he said.

This work is in the early stages in which the first goal is to find the linkage between what is known about some materials and what scientists can extrapolate based on the available experiments and data.

Alexander said the aerospace industry has “models of everything they do.” They run “complex computer simulations [because] they want to know how they’d design something and which design to carry out.”

Alexander is currently the head of a co-design center, ExaLearn, that focuses on exascale, machine-learning technologies. The center is the sixth through the Exascale Computing Project. Growth in the amount of data and computational power is rapidly changing the world of machine learning and artificial intelligence. The applications for this type of technology range from computational and experimental science to engineering and the complex systems that support them.

Ultimately, the exascale project hopes to create a scalable and sustainable software framework for machine learning that links applied math and computer science communities to create designs for learning.

Alexander “brings to machine learning a strong background in science that is often lacking in the field,” Edward Dougherty, a distinguished professor in the Department of Electrical and Computer Engineering at Texas A&M, wrote in an email. He is an “excellent choice to lead the exascale machine learning effort at Brookhaven.”

Alexander is eager to lead an attempt he suggested would advance scientific and national security work at the Department of Energy. “There are eight national laboratories involved and all the labs are on an equal level,” he said. 

One of the goals of the exascale computing project is to build machines capable of 10 to the 18th operations per second. “There’s this enormous investment of DOE” in this project, Alexander said.

Once the project is completely operational, Alexander expects that this work will take about 30 percent of his time. About 20 percent of the time, he’ll spend on other projects, which leaves him with about half of his workweek dedicated to management.

The deputy director recognizes that he will be coordinating an effort that involves numerous scientists accustomed to setting their own agenda.

Dougherty suggested that Alexander’s connections would help ensure his success, adding that he has “established a strong network of contacts in important application areas such as health care and materials.

The national laboratories are akin to players in a professional sporting league. They compete against each other regularly, bidding for projects and working to be the first to make a new discovery. Extending the sports metaphor, members of these labs often collaborate on broad projects, like players on an all-star team competing against similar teams from other nations or continents.

Alexander grew up in Ohio and wound up working at Los Alamos National Laboratory in New Mexico  for over 20 years. He came to BNL in 2017 because he felt he “had the opportunity to build something almost from the ground up.” The program he had been leading at Los Alamos was large and well developed, even as it was still growing. 

The experimental scientists at BNL have been receptive to working with Alexander, which has helped him achieve some of his early goals.

Ultimately, Alexander hopes his work increases the efficiency of numerous basic and applied science efforts. He hopes to help experimental scientists understand “what technologies we should develop that will be feasible” and “what technologies would be most useful to carry experiments out.”

Stony Brook University Hospital. File photo

Most people only think about Lyme disease when taking a hike in a park, but for many doctors, the condition weighs heavily on their minds every day.

Dr. Benjamin Luft, director and principal investigator of Stony Brook WTC Wellness Program, is one of those doctors. He is currently working on two clinical studies examining the disease. One involves those who continue to present symptoms after being treated, and the other study involves Latinos on Long Island who work in the landscaping and agricultural fields.

In a recent phone interview, Luft said the clinical study involving Latinos is a straightforward one, where the aim is to help a population that has been underserved and understudied due to their work schedules. The other study is more involved.

After being bitten by a tick infected with a bacterium called Borrelia burgdorferi, many people with a bull’s eye rash or flulike symptoms may receive treatment and feel better; but there are those who will continue to suffer for a prolonged period, even years, with a variety of complaints like aches, pains and brain fogginess. Luft said at times there may be no clear signs of the disease in the body, but doctors may find evidence of it after thorough neuropsychological exams that can detect subtle abnormalities.

Dr. Benjamin Luft is one of the doctors at Stony Brook Medicine looking for answers when it comes to those who continue to suffer from Lyme disease after treatment. Photo from Stony Brook Medicine

“This study is really geared toward diagnosing and to find ways to be able to monitor the disease,” Luft said, adding in the future his hope is to conduct studies testing new ways to treat Lyme disease.

The doctor said it’s essential to receive a diagnosis because if Lyme disease is left untreated, it can lead to joint swelling, arthritis, neuropathies, meningitis or cardiac problems.

When Stony Brook University recently began making a more significant investment in its imagining facilities, Luft said he saw a chance to find an answer for those with chronic symptoms.

“I thought this is the opportunity to see what is going on in the brain of these patients with using X-ray techniques and radiological techniques which may give us some insight,” he said.

He said with cutting-edge neuroimaging studies researchers can look for evidence of inflammation in the brain which may be a reaction to the infection.

“That would be an important thing to do because it may give us another target for therapy,” Luft said. “A lot of the therapy that we now use is really just geared toward the organism itself, but it’s not really geared toward the body’s reaction to the organism which may also have to be treated in order to alleviate some of these symptoms.”

The doctor has studied Lyme disease for more than 30 years. When he arrived at SBU from Stanford University Hospital, he was involved in work with AIDs and age-related diseases, but he said at the university’s clinic in the 1980s many people complained of Lyme disease problems and there were no effective therapies at the time. Many of the first therapies and treatments used today were developed at SBU, he said, but there have always been people who haven’t responded well to those treatments.

“So that’s been something that’s been bothering me for many years as to why that is,” Luft said.

He said he will present initial data, which is promising, from the clinical imagining study at a conference in Barcelona, Spain, later this month and hopes to get more patients for the clinical study. Those who are interested can call 631-601-5615. Subjects must meet stringent criteria including not having any other disease, having serological evidence of Lyme disease and a clear history that they had the rash.

In addition to Luft’s studies, Dr. Christy Beneri, assistant professor of pediatrics at SBU, and her team are working on a pilot study to look at newer diagnostic tools to establish a better way to diagnose early Lyme disease.

“We also will be doing work on understanding tick epidemiology in our area and working with the local health department to understand potential new tick-borne pathogens,” Beneri said.

Stony Brook Lyme Disease Laboratory has been performing Lyme disease testing on clinical specimens since 1984. Both inpatients and outpatients can have a Lyme ELISA screening test and Western blots confirmatory test at Stony Brook Medicine. Almost 10,000 screenings were done in 2017 at the hospital, which has been actively working with state senators for funding for Lyme disease outreach and research, according to Beneri.

Giovanni Alfonso Borelli

By Elof Axel Carlson

Elof Axel Carlson

Scientists have a tradition of citing those whose work helped shape their own ideas and experiments. Almost every scientific paper has a list of such journal articles or books cited by the authors of a published article in a peer-reviewed journal. Usually these references are to recent work that the author or authors have read. 

But one could chase back the references of each cited article and keep doing this to work that was published in the 1600s. Before that things get more complicated because science as we know it dates to the Renaissance. Most of those cited names are forgotten to us and we are taught the names of only a few of these many scientists. 

Thus, we single out the major contributors like Galileo and his work supporting the Copernican theory that Earth and other planets move around the sun. We cite Vesalius’s work on human anatomy, the first accurate depiction of the organs of the human body. We also cite Harvey’s work on the circulation of the blood. What these all have in common is the belief that living organisms are like machines and the laws of physics apply to interpreting their structure and function. 

One of the forgotten contributors to this view of life was Giovanni Alfonso Borelli (1608–1679). Born in Naples, he was the son of a Spanish father, Miguel Alonso, and an Italian mother, Laura Porrello. His father had been exiled from Spain for association with a heretic. This led young Giovanni at the age of 20 to change his baptismal name from Giovanni Francesco Antonio Alonso to the fully Italian sounding Giovanni Alfonso Borelli, which was a version of his mother’s surname Porrello. 

At that time Naples was a Spanish colony and Borelli grew up with his sympathies for Italian culture and political rule. He became a mathematician and astronomer first. He worked out the orbits of Galileo’s discovery of the four large moons of Jupiter and showed they were ellipses. He showed that a comet of 1664 had a parabolic path and was farther than the moon, contradicting church belief then that the comets were not as far as the moon. Isaac Newton cited his work.  

Borelli shifted to medicine and showed that the motions of animals was caused by muscle contractions and the mathematics of levers, pulleys and other machines applied to the components of the body that he studied. He rejected the prevailing view that motion was caused by a vital fluid in the muscles coming from nerves by cutting muscles and showing no such fluids were released. Instead he worked out the center of gravity for different activities of animals and founded the field of biomechanics.  

He kept moving whenever his Spanish ancestry was revealed or when he contradicted fellow scientists who clung to Aristotelian theories that Borelli rejected as nonscientific. In his later life while writing his works, he was supported by Queen Christina of Sweden who went into exile in Rome after converting to Catholicism. He taught mathematics in the convent school that she established and she paid for the publication of his book on animal motion that he dedicated to her.  

Elof Axel Carlson is a distinguished teaching professor emeritus in the Department of Biochemistry and Cell Biology at Stony Brook University.

Above, Brian Colle, who enjoys surf fishing, with a false albacore that he caught at the Shinnecock Inlet. Photo by B. Colle

By Daniel Dunaief

In August of 2014, Islip experienced record rainfall, with over 13 inches coming down in a 24-hour stretch — more than the typical rainfall for an entire summer and a single day record for New York state. The rain required emergency rescues for motorists whose cars suddenly died after more than 5 inches of rain fell in a single hour.

What if, however, that rain had fallen just 50 miles west, in Manhattan, where the population density is much higher and where people travel to and from work on subways that can become flooded from storms that carry less precipitation?

An image of an ice crystal Colle examined during a Nor’easter. Image from B. Colle

Brian Colle, professor of atmospheric sciences and director of the Institute for Terrestrial and Planetary Atmospheres at the School of Marine and Atmospheric Sciences at Stony Brook University, is part of a group that is studying flood risks in the New York metro area during extreme storms that could bring heavy rains, storm surge or both. The team is exploring mitigation strategies that may help reduce flooding.

“The risk for an Islip event for somewhere in the NYC-Long Island area may be about one in 100 years (but this is being further quantified in this project), and this event illustrates that it is not a matter of whether it will occur in NYC, but a matter of when,” Colle explained in a recent interview.

The group, which is led by Brooklyn College, received $1.8 million in funding from New York City’s Department of Environmental Protection and the Mayor’s Office of Recovery & Resiliency. It also includes experts from The New School, the Stevens Institute of Technology and Colorado State University.

The co-principal investigators are Assistant Professor Brianne Smith and Professor Jennifer Cherrier, who are in the Department of Earth and Environmental Sciences at Brooklyn College–CUNY.

Smith, who had worked with Colle in the past, had recruited him to join this effort. They had “been wanting to do studies of flooding for New York City for a long time,” Smith said. “When the city came out with this” funding for research, Colle was “the first person I thought of.”

Malcolm Bowman, a distinguished service professor at Stony Brook University, holds his colleague, whom he has known for a dozen years, in high regard. Colle is “a leading meteorologist on regional weather patterns,” he wrote in an email. 

Colle is interested in the atmospheric processes that produce rainfall of 2 or 3 inches per hour. “It takes a unique part of the atmosphere to do that,” he said. The three main ingredients are lots of moisture, lift along a wind boundary, and an unstable atmosphere that allows air parcels, or a volume of air, to rise, condense and produce precipitation.

Representatives from the local airports, the subway systems and response units have been eager to get these predictions, so they can prepare mitigation efforts.

Brooklyn College – CUNY project co-leads Brianne Smith (left) and Jennifer Cherrier at Grand Army Plaza in Brooklyn in early September. Photo by John Mara

This group has taken an ambitious approach to understanding and predicting the course of future storms. Typically, scientists analyze storms using 100- to 200-kilometer grid spacing. In extreme rainfall events during coastal storms, scientists and city planners, however, need regional spacing of 20 kilometers. Looking at storms in finer detail may offer a more realistic assessment of local precipitation.

Researchers are anticipating more heavy rainfall events, akin to the one that recently caused flooding in Port Jefferson.

A warmer climate will create conditions for more heavy rains. Water vapor increases about 6 to 7 percent for every degree increase in Celsius. If the climate rises two to four degrees as expected by the end of the century, this would increase water vapor by 13 to 25 percent, Colle said.

The group includes experts from several disciplines. “Each of the scientists is highly aware of how integrative the research is,” Cherrier said. The researchers are asking, “How can we provide the best scientific foundation for the decisions” officials need to make. If, as predicted, the storms become more severe, there will be some “hard decisions to make.”

Smith suggested that a visible project led by women can encourage the next generation of students. Women undergraduates can appreciate the opportunity their female professors have to lead “cool projects,” she said. 

Raised from the time he was 4 in Ohio, Colle said he was a “typical weather geek” during his childhood. The blizzard of 1978 fascinated him. After moving to Long Island in 1999, Colle used to sit in a weather shed and collect ice crystals during nor’easters. He would study how the shape of these crystals changed during storms. An avid surf fisherman, Colle said there is “not a better place to observe weather” than standing near the water and fishing for striped bass, fluke, bluefish and false albacore. A resident of Mount Sinai, Colle lives with his wife Jennifer, their 16-year-old son Justin and their 13-year-old son Andrew.

As for his work on flood risks around the New York metro area, Colle said the group is producing monthly reports. The effort will end in December. “The urgency is definitely there,” he acknowledged. Heavy rainfall has increased the need to understand rain, particularly when combined with surge flooding.

A transportation study written over a decade ago describes storm surge and rainfall risk. That study, however, included a prediction of 1 to 2 inches of rainfall an hour, which is far less than the 5 inches an hour that hit Long Island in 2014.

“Once you start seeing that, there’s a lot of people who are nervous about that risk and want to get a best estimate of what could happen,” Colle said.

Cherrier described New York City as being “quite progressive” in gathering information and formulating data. “The city wants to be prepared as soon as possible.”

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