Science & Technology

Standing near one of the X-ray scattering instruments, Kevin Yager holds a collection of samples, including a self-assembling polymer film. Photo courtesy of BNL

By Daniel Dunaief

Throw a batch of LEGOs in a closed container and shake it up. When the lid is opened, the LEGOs will likely be spread out randomly across the container, with pieces facing different directions. Chances are few, if any, of the pieces will stick together. Attaching strong magnets to those pieces could change the result, with some of the LEGOs binding together. On a much smaller scale and with pieces made from other parts, this is what researchers who study the world of self-assembled materials do.

Scientists at the Center for Functional Nanomaterials and at the National Synchrotron Light Source II at Brookhaven National Laboratory experiment with small parts that will come together in particular ways based on their energy landscapes through a process called self-assembly.

Every so often, however, a combination of steps will alter the pathway through the energy landscape, causing molecules to end up in a different final configuration. For many scientists, these so-called nonequilibrium states are a nuisance.

Above, Kevin Yager listens to sonified data. When data is sonified, it is translated into sound. Photo by Margaret Schedel

For Kevin Yager, they are an opportunity. A group leader at the CFN who works closely with the NSLS-II, the McGill University-educated Yager wants to understand how the order of these steps can change the final self-assembled product. “In the energy landscape, you have these peaks and valleys and you can take advantage of that to move into a particular state you want,” Yager said. “The high level goal is that, if we understand the fundamentals well enough, we can have a set of design rules for any structure we can dream up.”

At the CFN, Yager manages a nanofabrication facility that uses electron-beam lithography and other techniques to make nanostructures. He would like to fabricate model batteries to show the power of nanomaterials. He is also determined to understand the rules of the road in the self-assembly process, creating the equivalent of an instruction manual for miniature parts.

In future years, this awareness of nonequilibrium self-assembly may lead to revolutionary innovations, enabling the manufacture of parts for electronics, drugs to treat disease and deliver medicine to specific locations in a cell and monitors for the detection of traces of radioactivity or toxins in the environment, among many other possibilities.

Yager’s colleagues saw considerable opportunities for advancement from his work. Nonequilibrium self-assembly has “significant potential for a broad range of nanodevices and materials due to its ability to create complex structures with ease,” Oleg Gang, a group leader in Soft and Bio Nanomaterials at the CFN, explained in an email. Yager is an “excellent scientist” who produces “outstanding results.”

One of the things Yager hopes his research can develop is a way to “trick self-assembly into making structures they don’t natively want to make” by using the order of steps to control the final result.

As an example, Yager said he developed a sequence of steps in which nanoscale cylinders pack hexagonal lattices into a plane. These lattices tend to point in random directions as the cylinders form. By following several steps, including sheer aligning a plane and then thermal processing, the cylinders flip from horizontal to vertical as they inherit the alignment of the sheered surface. Flipping these cylinders, in turn, causes the hexagons all to point in the same direction. When Yager conducted these steps in a different order, he produced a different structure.

Broadly speaking, Yager is working on stacking self-assembling layers. In his case, however, the layers aren’t like turkey and swiss cheese on a sandwich, in which the order is irrelevant to the desired final product. Each layer has a hand in directing the way the subsequent layers stack themselves. Choosing the sequence in which he stacks the materials controls their structure.

Yager is working with Esther Takeuchi and Amy Marschilok at Stony Brook University to develop an understanding of the nanostructure of batteries. Gang suggested that Yager’s expertise is “invaluable for many scientists who are coming to the CFN to characterize nanomaterials using synchtrotron methods. In many cases, it would probably be impossible to achieve such quantitative understanding without [Yager’s] input.”

Yager and his wife Margaret Schedel, an associate professor in the Department of Music at Stony Brook University who is a cellist and a composer, live in East Setauket. The couple combined their talents when they sought ways to turn the data produced by the CFN, the NSLS and the NSLS-II into sound.

Scientists typically convert their information into visual images, but there’s “no reason we can’t do that with sound,” Yager said. “When you listen to data, you sometimes pick up features you wouldn’t have seen.”

One of the benefits of turning the data into sound is that researchers can work on something else and listen to the collection of data in the background, he said. If anything unexpected happens, or there is a problem with a sample or piece of equipment, they might hear it and take measures more rapidly to correct the process. “This started as a fun collaboration,” Yager said, “but it is useful.”

Schedel is working on sonifying penguin data as well. She also sonified wave data on Long Island. “By listening to the tides quickly, larger patterns emerge,” she said, adding that Yager thought the idea was theoretically interesting until he listened to misaligned data and then he recognized its benefit.

Schedel’s goal is to see this sonification effort spread from one beamline to all of them and then to the Fermilab near Chicago and elsewhere. She wants sonification to become “an ear worm in the science community.”

While Schedel introduced Yager to the world of sound in his research, he introduced her to sailing, an activity he enjoyed while growing up in the suburbs of Montreal. When she sails with him, they are “half in and half out of the boat,” Schedel said. It’s like two people “flying a kite, but you are the kite. You have to learn how to counterbalance” the boat. They hike out so they can take turns faster without tipping over, she said.

The Tesla Science Center at Wardenclyffe is located at 5 Randall Road in Shoreham. File photo by Wenhao Ma

Shoreham’s Tesla Science Center at Wardenclyffe is hosting the Electric Dream Expo Saturday, July 8 — a community event honoring science innovator Nikola Tesla’s 161st birthday, as well as the 100th anniversary of the dismantling of Tesla’s famous wireless transmitting tower. The Electric Dream Expo is comprised of an afternoon Science & Innovation Expo from 2 to 6 p.m. on the site of Tesla’s last existing laboratory in Shoreham, with exhibits, demonstrations, food and entertainment.

There will also be an evening of Tesla entertainment, called Summer Electrified!, from 8 to 10 p.m. at Shoreham-Wading River High School, 250A Route 25A, Shoreham, featuring Tesla-inspired performances.

Technological innovation of the past, present and future is the expo’s theme, and attendees at the daytime Science & Innovation Expo will experience Tesla-themed exhibits and activities for all ages, including a HAM radio presentation, displays by The Museum of Interesting Things and Long Island Radio & TV Historical Society, Tesla coil exhibit, 3-D printer and robotics demos, interactive exhibits of Tesla inventions and a Tesla car display.

Tours and a special presentation of innovation will feature the history of Tesla’s 187-foot wireless transmitter tower, built on the Shoreham site in 1907 and dismantled 100 years ago. The tower’s base remains as a focal point, along with Tesla’s Wardenclyffe Laboratory, built from 1901 to 1905 by renowned architect Stanford White, and now being renovated into an immersive science and education center.

The Summer Electrified! an evening of Tesla entertainment, features ArcAttack!, a musical light show using Tesla coil technology, as well as a unique lineup of performances and readings focused on Tesla’s life and legacies.

Admission to the Science & Innovation Expo is $15 for ages 13 and over, $5 for ages 5 to 12 and free for children under 5. Tickets for the Summer Electrified! performances are $25 per person 13 and over, $12 for ages 5 to 12 and free for children under 5. Admission to both events is $35 for 13 and over, $15 for ages 5 to 12 and free for children under 5. A special price of $25 per car covers admission to the daytime Science Innovation Expo for all passengers, and is limited to the first 50 car tickets purchased. Tickets can be purchased at www.teslasciencecenter.org.

HXN team members, from left, Evgeny Nazaretski, Ken Lauer, Sebastian Kalbfleisch, Xiaojing Huang, Yong Chu, Nathalie Bouet and Hanfei Yan. Photo courtesy of BNL

By Daniel Dunaief

There’s precision in measurements and then there’s the world of Yong Chu. The head of a beamline that’s housed off to the side in a separate, concrete structure from similar efforts at Brookhaven National Laboratory, Chu led the design, construction and commissioning of a sophisticated beamline with a resolution of as low as 3 nanometers, which he hopes will get down to 1 nanometer within a year.

Just as a measure of contrast, a human hair is about 80,000 nanometers wide. Why so fine a resolution? For starters, seeing objects or processes at that high level can offer insights into how they function, how to improve their manufacture or how to counteract the effects of harmful processes.

With a battery, for example, the Hard X-ray Nanoprobe, or HXN beamline, could help reveal structural weaknesses in the nanostructure that could cause safety issues. In biology, numerous functions involve sub-cellular organelles that respond to proteins. Proteins are typically smaller than the HXN beamline can image, although researchers can tag the proteins with metals, which allows Chu, his colleagues and visiting scientists to see an aggregate of these proteins.

The HXN beamline can also help explore environmental problems, such as how plants transport harmful nanoparticles to their fruits or how artificial compounds absorb nuclear waste. Imaging beamlines that use micro-focused beams typically offer spatial resolution of 10 microns, 1 micron or even 100 nanometers, according to Ryan Tappero, the head scientist at the X-ray Fluorescence Microprobe at BNL, who has used the HXN for his research. Using the NSLS II source properties and a new x-ray optics development routinely offers resolution of 10 nanometers, which pushes the spatial resolution down by another factor of 10, which makes the HXN, according to Tappero, a “game changer.”

Tappero described Chu as a “rock star” and suggested he was an “exceptional beamline scientist” who is “very knowledgeable about X-ray optics.”

BNL houses 19 beamlines at the National Synchrotron Light Source II, a state-of-the-art facility large enough that scientists ride adult tricycles inside it to travel from one beamline to another and to transport supplies around the facility. BNL is building another nine beamlines that it hopes to have operational within the next 18 months. Each of these beamlines offers a different way to explore the world of matter. Some beamlines do not use a focused beam, while others produce beams with high angular or high energy resolution. Imaging beamlines such as the HXN produce a small beam size.

The HXN beamline has the highest spatial resolution of any beamline at the NSLS-II. Scientists building the HXN grew a nanofocusing lens with a dedicated deposition system that was constructed at the NSLS-II Research and Development lab. The system grew a nanofocusing lens a layer at a time, alternating materials and controlling the thickness at better than 1 nanometer, Chu explained.

The beamline where Chu works has padded walls, a door separating it from the rest of the light source and a monitor that records the temperature to the thousandths of a degree. “We are constantly monitoring the temperature around the X-ray microscope and inside of the X-ray microscope chamber,” he said. Around the microscope, he can keep the temperature stable within 0.03 degree Celsius. In the chamber, the scientists maintain the temperature at better than 0.003 degree Celsius.

So, now that Chu and his colleagues built their beamline, have the scientists come? Indeed, the interest in using the HXN has been well above the available time slots. For the three cycles each year, BNL receives about four requests for each available time. This reflects the unique qualities of the instrument, Chu said, adding that he doesn’t expect the rate to drop considerably, even as the HXN continues to operate, because of the ongoing demand.

Researchers have to go through a peer review process, where their ideas are graded for the likelihood of success and for the opportunity to learn from the experiments. All beam time proposals are reviewed by external expert panels, which examine the scientific merit, appropriateness of use of the facility, capability of proposers and quality of prior performance and the research plan and technical feasibility.

Chu fields about 10 calls per month from scientists who want to speak with him about the feasibility of their ideas. He may suggest another station at the NSLS-II or at the Advanced Photon Source at Argonne National Laboratory in Chicago, where he was a beamline scientist starting in 1999.

“I know many of the beamlines” at the Advanced Photon Source, he said. “I recommend some of the potential users to perform experiments at the APS first before coming to the HXN.” By the time scientists arrive at his beamline, Chu said he’s gotten to know them through numerous discussions. He considers them “as a guest” at the HXN hotel. “We try to make sure the experimental needs for the users are met as much as possible,” he said.

The HXN beamline has three staff scientists and two postdoctoral fellows who remain in contact with scientists who use the facility. “For most of the users, at least one of us is working throughout the weekends and late evenings,” said Chu.

Not just a staff scientist, Chu is also a user of the HXN, with currently one active general user proposal through a peer review process in which he is collaborating with Stony Brook University and BNL scientist Esther Takeuchi to explore the nanostructure of metal atoms during phase separation in batteries.

Chu and his wife Youngkyu Park, who works at Cold Spring Harbor Laboratory as a research investigator in basic and preclinical cancer research, live in Northport. The couple’s 22-year-old son Luke is attending Nassau Community College and is planning to transfer to Stony Brook this fall to study engineering. Their daughter Joyce is 18 and is enrolled in the Parsons School of Design in New York.

Chu grew up in Seoul, South Korea, and came to the United States when he was 18. He attended Caltech. While Chu’s parents wanted him to become a doctor, he was more inspired by a cartoon called Astro Boy, in which a scientist, Dr. Tenma, is a hero solving problems. As for the work of the scientists who visit his beamline, Chu said the “success of individual users is the success of the beamline.”

SBU graduate student and grand niece of world renowned anthropologist Richard Leakey, Acacia Leakey, draws a sketch of huts in the village of Ambodiaviavy, Madagascar as the children look on. Photo from Mickie Nagel

By Daniel Dunaief

 

Mickie Nagel recently returned from the island nation of Madagascar, and she’s filled with ideas, inspiration, observations and opportunities. One of the three founders of a new nongovernmental organization called BeLocal, the Laurel Hollow resident spent several weeks with Stony Brook University graduate students Leila Esmailzada and Acacia Leakey taking videos and gathering information about life in Madagascar.

The goal of the new organization is to share this footage and insight with undergraduate engineers at SBU, who might come up with innovations that could enhance the quality of life for the Malagasy people.

In one village, a man showed her a three-inch lump on his shoulder, which he got by dragging a long stick with bunches of bananas that weigh over 100 pounds along a clay footpath out of the forest. People also carry rice that weighs over 150 pounds on their heads, while many others haul buckets of water from rivers and streams to their homes while walking barefoot.

In addition to transportation, Nagel also found that villagers around Centre ValBio, a Stony Brook research station, had basic food and water needs. Over 17 years ago, another group had installed four water pumps in a village to provide access to water. Only one pump now works.

SBU graduate student Leila Esmailzada helps villagers in Ambodiaviavy, Madagascar, clean rice. The job is usually delegated to the children who pound the rice for 30 minutes. Photo by Mickie Nagel

As for food, some villagers in Madagascar spend hours preparing rice, including beating off the husks and drying the rice. They store this hard-earned food in huts that are often infiltrated with rats, who consume their rice and leave their feces, which spreads disease.

Traveling with Esmailzada and Leakey, Nagel not only helped document life in these villages but also searched for information about available resources to drive engineering innovations, while Leakey gathered information about an invasive species of guava.

“Ideally, if any projects require wood, then they should incorporate guava sticks into their design, as opposed to planks from forest trees,” explained Leakey in an email sent from Madagascar. The graduate student, who recently earned her bachelor’s degree at Stony Brook, will be recording the average thickness of the stems, the average length of a straight piece and the load capacity of the branches. Leakey plans to return from the African continent in the beginning of August.

Leakey also visited metalworkers to explore the local capacity. The raw materials come from scrap metal dealers, who often get them from old car parts.

Nagel started BeLocal with her husband Jeff Nagel and a classmate of his from their days as undergraduates at Carnegie Mellon University, Eric Bergerson. Indeed, BeLocal fulfills a long-standing goal of Jeff Nagel’s. Before freshman year in college, Nagel told Bergerson that he wanted to do something that had a positive impact on the world.

While the founders have contributed through their work, their jobs and their families, they found that partnering with Stony Brook University and Distinguished Professor Patricia Wright in Madagascar presented a chance to have a meaningful impact on life on the island nation.

Nagel, whose background is in marketing, visited Madagascar over two years ago, where she traveled for over a hundred hours on a bus through the country. “You just see people living below the poverty line and you see how that plays out in normal day-to-day activities,” she said. “You see a young mom carrying a child on her back and one on her front, with heavy produce on her head and you just think, ‘Wow, there has to be an easier way for some of this.’”

Mickie Nagel, far right, on an earlier trip to Central ValBio with her daughters Gabrielle, far left, and Lauren, center. when they first visited Centre ValBio. Photo by Heidi Hutner

When Nagel returned from her initial trip to Madagascar with her daughters Gabrielle, 18, and Lauren, 17, she and her husband thought people around the world would likely want to help but that not everyone could afford to travel that far.

Nagel recalls Bergerson, who is the director of research at the social data intelligence company Tickertags, telling her that they “don’t have to travel there. You can videotape the daily challenges and crowd source” innovations.

That’s exactly what Leakey and Esmailzada did for the last few weeks. Leakey said she is looking forward to working with senior design students as they go through their projects at Stony Brook and is eager to see how they understand the situation “through the footage and pictures we collect.”

The BeLocal approach isn’t limited to Madagascar, the BeLocal founders suggested. Indeed, given the distance to an island famous for its lemurs, animated movies and an Imax film that features primates with personality, BeLocal could have started in a Central American country like Belize.

Mickie Nagel, however, urged them to start at a location where they would immediately have the trust of local residents. That, she suggested, came from the over quarter of a century of work from Wright, an award-winning scientist who has not only helped preserve Ranomafana [National Park in Madagascar] but has also helped bring health care and education to the villages around the CVB research station. Wright and the Malagasy people have a “mutual respect for each other,” Nagel said.

“People have been exceptionally warm and welcoming,” Leakey said. Getting people accustomed to the presence of cameras hasn’t been straightforward, as people sometimes stop what they are doing, but the guides have helped make the villagers more comfortable.

Jeff Nagel, who works at a private equity firm in New York City, explained that Madagascar is the first step for BeLocal. This effort “can be expanded to other countries or other areas,” Nagel said. “It doesn’t have to be engineers and universities,” but can be instituted by creative people everywhere.

At this point, BeLocal is not looking for any additional funding but might consider expanding the effort at this time next year. Nagel said this fall, they will look for professional engineers to advise on projects. “We would like people who are interested in participating or just keeping up with developments to come and register on our website, www.BeLocalgrp.com,” she suggested.

The site, which the group is upgrading, is up and running. Bergerson explained that they have a “lot of infrastructure to build on” to create the crowd sourcing platform.

Jeff Nagel suggested that this effort is designed to use technology constructively. “Technology’s job, first and foremost, is to help humanity,” he said. “This is a chance to use it in a way that matters to people.”

Priya Sridevi with her golden doodle Henry. Photo by Ullas Pedmale

By Daniel Dunaief

Priya Sridevi started out working with plants but has since branched out to study human cancer. Indeed, the research investigator in Cold Spring Harbor Laboratory Cancer Center Director David Tuveson’s lab recently became the project manager for an ambitious effort coordinating cancer research among labs in three countries.

The National Cancer Institute is funding the creation of a Cancer Model Development Center, which supports the establishment of cancer models for pancreatic, breast, colorectal, lung, liver and other upper-gastrointestinal cancers. The models will be available to other interested researchers. Tuveson is leading the collaboration and CSHL Research Director David Spector is a co-principal investigator.

The team plans to create a biobank of organoids, which are three-dimensional models derived from human cancers and which mirror the genetic and cellular characteristics of tumors. Over the next 18 months, labs in Italy, the Netherlands and the United States, at Cold Spring Harbor Laboratory, expect to produce up to 150 organoid models.

The project officially started in January and the labs have been setting up the process through June. Sridevi is working with Hans Clevers of the Hubrecht Institute, who pioneered the development of organoids, and with Vincenzo Corbo and Aldo Scarpa at the University and Hospital Trust of Verona.

Sridevi’s former doctoral advisor Stephen Alexander, a professor of biological sciences at the University of Missouri, said Sridevi has had responsibilities beyond her own research. She was in charge of day-to-day operations in his lab, like ordering and regulatory reporting on radioactive material storage and usage, while he and his wife Hannah Alexander, who was Sridevi’s co-advisor, were on sabbatical. “She is hard working and determined,” said Alexander. “She knows how to get things done.”

In total, the project will likely include 25 people in the three centers. CSHL will hire an additional two or three scientists, including a postdoctoral researcher and a technician, while the Italian and Netherlands groups will also likely add another few scientists to each of their groups.

Each lab will be responsible for specific organoids. Tuveson’s lab, which has done considerable work in creating pancreatic cancer organoids, will create colorectal tumors and a few pancreatic cancer models, while Spector’s lab will create breast cancer organoids.

Clevers’ lab, meanwhile, will be responsible for creating breast and colorectal organoids, and the Italian team will create pancreatic cancer organoids. In addition, each of the teams will try to create organoids for other model systems, in areas like lung, cholangiocarcinomas, stomach cancer, neuroendocrine tumors and other cancers of the gastrointestinal tract.

For those additional cancers, there are no standard operating procedures, so technicians will need to develop new procedures to generate these models, Sridevi said. “We’ll be learning so much more” through those processes, Sridevi added. They might also learn about the dependencies of these cancers during the process of culturing them.

Sridevi was particularly grateful to the patients who donated their cells to these efforts. These patients are making significant contributions to medical research even though they, themselves, likely won’t benefit from these efforts, she said. In the United States, the patient samples will come from Northwell Health and the Tissue Donation Program of Northwell’s Feinstein Institute of Medical Research. “It’s remarkable that so many people are willing to do this,” Sridevi said. “Without them, there is no cancer model.”

Sridevi also appreciates the support of the philanthropists and foundations that provide funds to back these projects. Sridevi came to Tuveson’s lab last year, when she was seeking opportunities to contribute to translational efforts to help patients. She was involved in making drought and salinity resistant rice and transgenic tomato plants in her native India before earning her doctorate at the University of Missouri in Columbia.

Alexander recalled how Sridevi, who was recruited to join another department at the University of Missouri, showed up in his office unannounced and said she wanted to work in his lab. He said his lab was full and that she would have to be a teaching assistant to earn a stipend. He also suggested this wasn’t the optimal way to conduct research for a doctorate in molecular biology, which is a labor-intensive effort. “She was intelligent and determined,” Alexander marveled, adding that she was a teaching assistant seven times and obtained a wealth of knowledge about cell biology.

Sridevi, who lives on campus at CSHL with her husband Ullas Pedmale, an assistant professor at CSHL who studies the mechanisms involved in the response of plants to the environment, said the transition to Long Island was initially difficult after living for six years in San Diego.

“The weather spoiled us,” she said, although they and their goldendoodle Henry have become accustomed to life on Long Island. She appreciates the “wonderful colleagues” she works with who have made the couple feel welcome.

Sridevi believes the efforts she is involved with will play a role in understanding the biology of cancer and therapeutic opportunities researchers can pursue, which is one of the reasons she shifted her attention from plants. In Tuveson’s lab, she said she “feels more closely connected to patients” and is more “directly impacting their therapy.” She said the lab members don’t get to know the patients, but they hope to be involved in designing personalized therapy for them. In the Cancer Model Development Center, the scientists won a subcontract from Leidos Biomedical Research. If the study progresses as the scientists believe it should, it can be extended for another 18 months.

As for her work, Sridevi doesn’t look back on her decision to shift from plants to people. While she enjoyed her initial studies, she said she is “glad she made this transition” to modeling and understanding cancer.

By Elof Axel Carlson

Elof Axel Carlson

Science is a way of interpreting the universe in the era in which we live. One of the realities of our lives is that we do not know how much of the world we think we know is really incomplete.

Think of it this way — If you grew up when the American Revolutionary War was being fought, you would not know a lot. You would not know your body is composed of cells. You would not know that heredity is transmitted by genes located on chromosomes present in nuclei of cells because no one knew there were nuclei, chromosomes or genes.

You would also not know there are biochemical pathways that carry out your metabolism in cell organelles because no one then knew there was such a thing as metabolism, biochemical pathways or cell organelles. And you would not know that infectious diseases are associated with bacterial and viral infections nor would you know that your body is regulated by hormones. If you created a time line of scientific findings in the life sciences, the cell theory was introduced in 1838. Cells were named in 1665, but Robert Hooke thought they accounted for the buoyancy of cork bark. He drew them as empty boxes.

When Schleiden and Schwann described cells, they were filled with fluid; and Schwann thought nuclei were crystallizing baby cells being formed in a cell. The cell doctrine (all cells arise from pre-existing cells) did not come until Remak and Virchow presented evidence for it. Mitosis, or cell division, was not worked out until the late 1870s; and meiosis of reproductive cells (sperm and eggs) was not worked out until the 1990s.

Fertilization involving one sperm and one egg was first seen in 1876, while most cell organelles were worked out for their functions and structure after the invention of the electron microscope in the 1930s. There was no organic chemistry before Wöhler synthesized molecules like urea in 1823, and biochemical pathways were not worked out until the 1940s.

DNA was not known to be the chemical composition of genes until 1944, the structure of DNA was worked out in 1953, molecular biology was not named until 1938 and the germ theory was worked out in the 1870s and 1880s by Pasteur and by Koch, who both demonstrated bacteria specific for infectious diseases. Embryology was worked out in 1759 by Wolff, while hormones were first named and found in 1903 by Bayliss and Starling.

What the history of the life sciences reveals is how dependent science is on new tools to investigate life. Microscopes up to 30 power came from Hooke’s efforts in 1665. A better microscope by Leeuwenhoek distinguished living organisms (“animalcules”) at up to 500 power.

It was not until the 1830s that microscopes were able to overcome optical aberrations and not until the 1860s that a stain technology developed to see the contents of cells. This boosted observation to 2000 power. For the mid-20th century, cell fractionation made use of centrifuges and chromatography to separate organelles from their cells and work out their functions.

Experimental biology began in England with Harvey’s study in 1628 of the pumping action of the heart. Harvey was educated in Padua, Italy, where experimental science had been stressed by Galileo and his students who began applying it to the motion of the body relating bones and muscles to their functions. No one alive in 1750 (or earlier) could have predicted DNA, oxidative phosphorylation, the production of oxygen by plants, Mendel’s laws of heredity or the role of insulin in diabetes.

But what about the present? How complete is our knowledge of life processes? Are there major findings in the centuries to come that will make our present understanding look as quaint as reading the scientific literature in the 1700s?

We can describe what we would like to know based on our knowledge of the present and likely to be achievable. We cannot predict what may turn out to be new functions or structures in cells. At best (using what we do know) we can hope to create a synthetic cell that will be indistinguishable from the living cell from which it was chemically constructed. But that assumes the 300 or so genes in a synthetic cell will account for all the activities of the vague cytoplasm in which metabolism takes place.

For the level of viruses there are no such barriers and the polio virus has been synthesized artificially in cell-free test tubes in 2002 (an accomplishment of Eckard Wimmer at Stony Brook University).

Within a few years ongoing studies of bacteria and of yeast cells with artificial chromosomes, may resolve that question for the genome of a eukaryotic cell. I hope that an artificial cytoplasm will be worked out in that effort. That might be more of a challenge than presently assumed.

On a sun-splashed Saturday afternoon, members of the community young and old had the chance to get outside and exercise their imagination at the third Eastern Long Island Mini Maker Faire. The popular event, hosted by the Port Jefferson Maritime Explorium June 10, saw demonstrations using robots, interactive activities, exhibits and performances from various “makers” at the Village Center and outside at Harborfront Park.

The Port Jeff maker faire is a scaled down version of the larger Maker Faire brand, which hosts worldwide events similar to the one in Port Jeff. According to the Maritime Explorium’s website, more than 100 makers and 2,000 participants attended the 2016 Mini Maker Faire, and even more were projected to show up this year, although final totals were not readily available.

Some of the makers on display included Funtown Studios, which brought an interactive fireball sculpture; robotics teams from the Sachem and Smithtown school districts; electricity and magnetism demonstrations by representatives from the Tesla Science Center at Wardenclyffe in Shoreham; an underwater robotic demonstration by SeaPerch; representatives from Stony Brook iCREATE, an innovation facility designed to encourage “innovation and entrepreneurial nature” of the Stony Brook University campus community; and many more.

Before the 2016 faire, Stephanie Buffa, a volunteer board member at the Explorium, explained the importance of the message of the event and the museum as a whole.

“Everything is at our fingertips,” she said in a phone interview. “If you’re sitting at the dinner table and somebody asks a question, you ‘Google’ it. It’s so easy to get answers that way…it’s so easy to get caught up in all of these pre-packaged things that we forget to sort of, do it yourself. You can be creative in so many ways. You don’t have to be a good artist and be able to draw beautiful pictures to be creative and to make things.”

Lauren Hubbard, founding president and former executive director of The Maritime Explorium, who is listed as a producer of the faire, said the day was a success, though attendance numbers are not available as of yet. She said in a phone interview the goal of the event is to show local people of all ages they have the creativity to be makers.

“It’s really about highlighting the entrepreneurial spirit,” she said. “It’s a great opportunity for young people to see how that process happens, how to create something completely new.”

Gabor Balazsi in his lab. Photo by Aleksandrs Nasonovs

By Daniel Dunaief

It started with a bang. When he was young and living with his parents, Gabor Balazsi’s curiosity sometimes got the better of him, at the expense of his parents’ house.

The future Henry Laufer associate professor of physical and quantitative biology at Stony Brook University was holding bare wires in his native home in Transylvania when he plugged in an appliance. The current surged through his body, preventing him from releasing the wires. Fortunately, his mother came in and “unplugged me.”

These days, Balazsi, is much more focused on the kinds of behavior that turns the instructions for a cell into something more dangerous, like cancer or a drug-resistant strain of a disease.

Balazsi recently received a $1.8 million, five-year grant from the National Institutes of Health to study how gene networks change, often to the detriment of human health, as is the case when they are active in cancer or when they are resisting treatment. The grant is called Maximizing Investigators’ Research Award.

“Cancer cells often don’t look the same in a matter of months and drug-resistant microbes may look the same in a matter of days,” Balazsi said. He would like to know “what causes them to change and how can we prevent them from changing to their advantage and our disadvantage?”

In a way, Balazsi is trying to figure out a code that is akin to the popular 1970s game Simon in which a player has to repeat a growing number of flashing lights and sounds. With each turn, the game increases the number of flashing lights and sounds, going from a single red, to red, green, yellow and green until the player can no longer recall the entire code.

He is looking for a similar key to a sequence of events that transforms a cell, except that in the cancer, there are millions of interacting lights, many of which are invisible. The cancer biologist tries to reconstruct the sequence in which some of these lights turned on by observing visible lights that are currently on.

He is exploring the “pattern that leads to the outcome” through changes of networks in yeast cells, he said. He is also hoping to explore pathogenic fungi. The pattern, he said, will change depending on the circumstances, which include the environment and initial mutations.

Scientists who have collaborated with Balazsi suggested his understanding of several scientific disciplines enables him to conduct innovative research.

“He bridges two fields, biology and biophysics, allowing him not only to describe biological processes but also to model them and make predictions that can then be tested,” Marsha Rosner, the Charles B. Huggins professor at the University of Chicago, wrote in an email.

While Balazsi doesn’t treat patients, he is focused on understanding and controlling the processes that lead a cell or group of cells to change from a uniform function and task to a heterogeneous one, where the cells may follow a different path using a previously inactive network of genes.

By understanding what causes these changes, he hopes to find ways to slow their progress or prevent the kind of deviations that lead to combinations that are destructive to humans, such as when the cellular machinery copies itself uncontrollably.

Balazsi and Rosner collaborated on one paper and are continuing to work together. “Our work demonstrates one mechanism by which cells move from a homogeneous population to a more complex population that contains cells that promote cancer,” Rosner explained. “This mechanism is not based on mutations in genes, but rather on changes in the way that genes interact with each other in cells.”

On a fundamental level, Balazsi explained that researchers have developed considerable understanding, but still not enough, of what happens in normal conditions. He is seeking to discover the logic cells use to survive under stressful conditions.

Balazsi would like to determine if there is “anything we can do to decrease the tendency of cells to deviate from normality,” he said.

Balazsi welcomes this new funding, which will give him the freedom to pursue research questions at a basic level. Instead of supporting a single project, this financial support contributes to multiple projects.

The next step in funding his lab will be to approach the National Cancer Institute. Without much experience in applying for cancer grants, Balazsi plans to attend a think tank workshop in June in Seattle. Attendance at this meeting, which is hosted by Sage Bionetworks and the NCI, required an application and selection of participants.

To some degree, Balazsi may be able to relate to the heterogeneity that he hopes to study in cells. A physicist by training, Balazsi explained that he “wandered into biology.” He would like to steer away from major trends that mobilize many researchers. If many people are working on something, he does not want to be enriching big crowds but would prefer to try new things and test new ideas.

A resident of East Setauket, Balazsi lives with his wife Erika and their daughter Julianna, who is 6. Julianna is already doing some experiments at home and is exploring the yard.

When Balazsi was young, his parents tried to encourage him to become a doctor, which didn’t work because he didn’t like blood or hospitals as a child. In addition to his unexpected electric shock, Balazsi also explored how ethanol burns while flowing, which caused some additional damage to his house. “My parents,” he recalled, “weren’t happy.”

As for his work, Balazsi would like his work with these first steps, in understanding cellular processes, will have a translational element for people some time down the road.

“Whatever we do, hopefully, they can be implemented in actual cancer cells that are coming from patients one day,” he said, or they could have some relevance for people who are attempting to fight off “pathogenic microbes.”

Fan Ye. Photo from SBU

By Daniel Dunaief

Fan Ye has a vision for the future filled with high service and efficiency that doesn’t involve butlers or personal attendants. The assistant professor of electrical and computer engineering in the College of Engineering and Applied Sciences at Stony Brook University is focused on creating smart environments in which window blinds open as people pull into their driveways, lights turn off in unoccupied rooms and the building guides a new student turn by turn through complex floors and hallways from entrance to the registrar’s office.

“The physical environment would be like a caring mother,” said Ye. It would sense and figure out people’s needs and “take care of the occupants inside the building.”

In Ye’s vision, which he estimates is about one year to decades away from a reality, objects that rely on people to turn them on or off, reposition them or alter their settings would have chips embedded in them, working together to create an environment that anticipates and learns in response to the need around it.

“With sensors, [a smart environment] can sense both physical conditions and human activities and adjust the environment in manners that create/improve comfort, safety, convenience” and the productivity of the occupant, he explained in an email.

Ye recently received a $450,000 award over the next five years from the National Science Foundation for early-career faculty for his study of smart environments. The prestigious award is the highest honor given by the government to scientists and engineers beginning their independent careers.

Initially, Ye is developing and testing a security system with the Stony Brook University Police Department and the Center of Excellence in Wireless and Information Technology that grants specific access to buildings or facilities depending on the specifications of an administrator.

Many of the buildings on campus have electric locks, which someone can open with a badge where there’s a badge reader. A badge, however “isn’t that flexible,” Ye said. If an administrator would like to grant someone one-time access to open a door that doesn’t provide ongoing access, that is difficult to do with a badge system.

“What’s lacking in this closed proprietary system is flexible access control, which can determine who has what access based on context factors,” he said. Ye, his team, the police department and the CEWIT are building a system that can enable greater flexibility that allows someone to open an office door for five minutes during a specific hour. “If any of these context factors is not satisfied, they don’t have access,” he said.

Ultimately, he would like to construct a system using modern mobile technology, like smartphones, instead of physical badges. The system would include embedded security that employs modern cryptography so a hacker or attacker can’t trick the system.

By using software and hardware security, Ye is hoping to develop a system that prevents the most common attacks at a reasonable cost, which he hopes would prevent someone from gaining access.

Ye is building real systems and testing them. The cost-benefit of these systems depends on the object. A motor to open and close a window would cost money to manufacture, install and operate. As with any technological innovation, he said, “the question comes down to, How do you invest versus how much do you get in return?”

Looking at the historical trend for computation resources, Ye said computing and storage costs are falling at an exponential rate, while the price for radio and sensing is also falling rapidly, although not at the same pace.

“I believe this trend will continue, especially for a lot of these objects that need small embedded systems” that can be manufactured at a scale with low cost, he continued. The process of turning the environment into an efficient, high-service system isn’t an all-or-nothing proposition. Consumers might decide to focus on the air-conditioning or heat use in their homes.

Other researchers are developing ways to harness the vibrational energy of movement or sound, which, conceivably, could power some of these electronics without requiring the delivery and consumption of more energy.

Ye recognizes that these parts can and will break down and require repair, just as dishwashers sometimes stop working and iPhones can lose a list of contacts. So many small electronic parts in a smart environment could seem like an invitation to malfunctions.

He likens the repair process to cloud computing, which allows small to medium-sized companies to rent computing resources from larger companies. “A smart environment, especially for public buildings like a university or office, could potentially run in a similar model,” he said. Individuals might rely on IT support from dedicated personnel who, like a superintendent in a building, could be responsible for a host of smart products.

A native of Hubei Province in China, Ye, who now lives in Setauket, loves to hike in national parks. His favorite is Canyonlands in Utah. Ye had worked at IBM for about 10 years before joining Stony Brook almost three years ago. While he was there, Ye worked on numerous projects, including distributed stream processing, cloud-based queueing and wide-area dependable messaging. “I learned tremendously at IBM,” he said.

Ye is “”well known and respected in the mobile and wireless computing research community,” Hui Lei, an IBM distinguished engineer, wrote in an email. “He conducted pioneering work on scalable message delivery, robust coverage and security in wireless sensor networks, which are well received and highly cited and closely related to the smart environment work he is doing now.”

Lei suggested that Ye’s experience and accomplishments provide him with a solid track record and he is “confident that [Ye] will be able to come up with innovative solutions in this area.”

Sen. Kenneth LaValle, wearing hat, sits with Brookhaven National Laboratory beamline scientist Dieter Schneider. Looking on from left, BNL Director Doon Gibbs; vice president for development at Cold Spring Harbor Laboratory, Charles Prizzi; NSLS-II director John Hill; and Stony Brook University associate vice president for Brookhaven affairs, Richard Reeder. Photo from Brookhaven National Laboratory

Thanks to the persistent support of state Sen. Ken LaValle (R-Port Jefferson), Brookhaven National Laboratory secured $15 million from New York State to add a state-of-the-art microscope that could contribute to advances in basic science and medicine.

The national laboratory will purchase a new cryo-electron microscope and will use the funds to create a building attached to its National Synchrotron Light Source II.

“Cryo-electron microscopy is an advanced imaging technology that will significantly accelerate scientists’ understanding of molecular structures and processes generally, including many impacts in understanding disease and in aiding drug discovery,” Doon Gibbs, the laboratory director of BNL, said in an email.

BNL will use the funds to purchase the first of what they hope will be four such new microscopes. The lab is finalizing a bid, which is due by June 30 for funds from the National Institutes of Health for three additional microscopes.

“There is an exponentially increasing demand for the type of bio-structural information that such machines provide, and so we are competing to become an East Coast based national facility to serve this rapidly growing community,” James Misewich, the associate director for energy and photon sciences at BNL said in an email.

Having a suite of microscopes would enable BNL to have a spectrum of capabilities to serve the needs of its scientists and of researchers from around the world who flock to the Upton-based lab to conduct their research.

The new facility will create jobs associated with running the cryo-EM, Misewich said. If BNL wins the NIH proposal to become a national cryo-EM facility, it would also employ additional scientists, engineers, technicians and administrators to run the user program.

Misewich said he hopes scientists at nearby Stony Brook University and Cold Spring Harbor Laboratory will benefit from the opportunity to use a combination of its X-ray and electron microscope probes.

Senior members of the BNL team credit LaValle for helping to secure the funds.

“The $15 million in New York State funding is the culmination of a two-year effort led by the senator to bring a cryo-EM to Brookhaven and jump-start this important effort,” Gibbs said.

LaValle suggested that the funds were well worth the investment.

“It is critically important for government to embrace and support the work of the organizations that make life-altering discoveries and better our lives, health and environment,” LaValle said in an email. “This investment will further establish world-leading prominence in the field of medical research, and position the region for additional major investments by the National Institutes of Health and the U.S. Department of Energy.”

Misewich envisions configuring one of the microscopes to allow for electron tomography, which will generate three-dimensional images of cells.

“The approach will be complementary to the X-ray imaging work we can undertake with the NSLS-II beamlines,” Misewich said.

Gibbs explained that the cryo-EM is complementary to X-ray crystallography, which is the traditional method for determining structures, which scientists already do at BNL.

“Few prescription drugs have been approved by the [Food and Drug Administration] for use in the U.S. in the last 20 years without a crystallographic study of their structure by X-rays,” Gibbs continued.

Misewich expects the new microscope could lead to new methods of detection, diagnosis and treatment for diseases like cancer or for medical challenges like antibiotic resistance.

Combining the technological tools of the new cryo-EM with the insights from the NSLS II and the nine-year-old Center for Functional Nanomaterials will enable researchers to “provide much more rapid bio-structure determination in response to needs like the ability to rapidly characterize a virus,” Misewich said.

LaValle sited this effort as a part of his ongoing commitment to build Long Island’s new high-tech economy.

The combination of BNL, SBU and CSHL “will provide a significant boost to the competitiveness of the biosciences and biotechnology communities across Long Island,” LaValle said.