It’s an issue that attracts debate because there are large enough overlapping or gray areas that make it challenging to offer a definitive answer across a range of circumstances.

“I had a professor in graduate school who put it this way: If you have the genetic variant for Huntington’s disease, you will get Huntington’s disease,” said W. Richard McCombie, a professor and director of the Stanley Institute for Cognitive Genomics at Cold Spring Harbor Laboratory. “If you walk in front of a truck that’s going 70 miles per hour on an interstate, your genes are irrelevant. Everything else is in between.”

Indeed, McCombie and his lab have become something of expert genetic speed readers, looking at enormous multiples of genes that were almost unthinkable just a decade or so ago.

“Next-generation sequencing has dramatically changed the field of genomics, allowing researchers to access an unprecedented amount of data,” he said. “The challenge lies in the analysis of these large data sets.”

The sequences he describes are the combination of the four base pairs, adenine, guanine, cytosine and tyrosine, strung together in a double-helix ladder design.

The implications of these new genetic sequences and libraries range from generating personalized medicine and understanding the prognosis for different diseases and likelihoods of effective therapy to seeking ways to enhance the production of food and energy crops.

The basic question he’s asking is “what’s the correlation between the structure and function of a living organism, in terms of the genome?”

From a practical standpoint, working in different systems helps when McCombie is applying for funding, he suggested.

The technology and expertise he develops also have applications across systems. When he gets funding to explore the sequence of large plant genomes, he can then use what he learns from that to work on studying cancer.

McCombie’s contributions have spanned several areas, including developing next-generation sequencing, contributing to plant genome sequencing and studying the genetic basis of cognitive disorders, said Greg Hannon, the Royal Society Wolfson Research Professor at the Cancer Research UK Cambridge Institute at the University of Cambridge, who has co-authored 17 papers with McCombie.

“He has made tremendous impacts across multiple fields,” Hannon said,

McCombie is “a real hero of the lab,” and Hannon said he “can’t think of anyone else who has had the diversity of impact he has.”

Sequencing in general has involved instruments that look at small bits of data at a time, around 100 base fragments. Using something called long-read technology, researchers can now examine pieces that are around 10,000 base pairs.

This technology is “really coming along” and has implications for cancer, where tumors are often due to rearrangements, insertions or deletions, while it also might impact plant genomics, where the long-read technology can be 100 to 1,000 times as effective as the short-read technology, McCombie said.

Sequencing pieces of genes is like taking a picture of, say, the Grand Canyon and turning that into a jigsaw puzzle. In the short-read technology, the pieces are smaller and, in some cases, show some of the same features. In the long-read technology, the pieces are much larger, turning the picture into something closer to a small child’s puzzle.

The long reads have a lower raw accuracy, he said, but with enough coverage, scientists can achieve a high consensus accuracy because the errors are mostly random.

The long-read technology is like having a puzzle with four pieces, instead of 1,000, he said.

The process of comparing genes or looking for a smoking gun causative set of genes involved in disease can be and is difficult, especially when comparing the genes of an individual with a representative healthy set of genes.

“Searching for causative genes can be very challenging particularly in complex diseases where more than one gene (and often many genes) contributes to the disease,” McCombie explained. “Trying to pinpoint causative variants is complicated by the normal background variation.”

Indeed, it’s more productive and instructive to look at larger sample sizes of people or to examine trios — the genes of parents unaffected by a genetic disease and their affected child.

Using these trios, McCombie and other scientists have found some overlap in potentially causative genes across disorders from schizophrenia and bipolar disorder to autism and intellectual impairment. McCombie is currently exploring multiple sets of genes in cases of depression.

McCombie and his wife Janice, a computer technician who works in Manhattan, live in Port Washington, which, he says, is convenient to the many operas they enjoy.

Given the flood of information available through all the genetic data that comes out daily, McCombie said scientists entering this field have to have some skill and understanding of bioinformatics, which makes sense of vast amounts of data.

“I give a short talk to the first-year grad students on their research every year,” he said. “One of them asked me if I thought bioinformatics was important in biology research. To be realistic, people in [the next generation] have no future if [they’re] not adept at working on computers and don’t understand bioinformatics.”

The battle is like a game of chess, with each side making moves and countermoves to gain the upper hand. The difference between this contest and a game two players can walk away from is that the stakes are considerably higher, often marking the difference between life and death.

Predicting the responses of enemies like drug-resistant infections and cancers are critical to winning the high stakes battle.

Gábor Balázsi, a Henry Laufer associate professor of physical and quantitative biology at Stony Brook University, has created a synthetic biological model to understand how systems react to stresses such as antibiotic treatments, or, to extend the metaphor, different moves on the chess board.

He inserted genetic codes into yeast. Some start-up companies have tried to employ these techniques to increase the efficiency of the production of energy or medications.

Companies “engineer bacteria to do something good, but will they be stable? Will they stay the way you engineered them? It’s important to know how long it’ll last, when it’ll break and when you should start a new culture,” Balázsi said.

Indeed, Balázsi used computer simulations and mathematical models to predict the evolutionary fate of these synthetic gene circuits and then tested these predictions through experiments.

In these experiments, Balázsi introduced drugs that would test the yeast’s ability to tap into the inserted genes and make the kind of changes necessary to survive. In some of the experiments, he introduced another chemical that could turn on the synthetic genes. He published this work recently in the scientific journal, Molecular Systems Biology.

In one of the experiments, Balázsi did not enable the yeast to activate the drug resistance gene, and yet, the yeast figured out how to use that gene on its own. These mutations happened in the synthetic gene circuit and in the yeast genome. The mutations gave the yeast the ability to turn on its inserted genetic code.

“The yeast figures out how to start activating those genes without us enabling it to do so,” he said.

This is akin to putting a trombone next to a saxophone player, without teaching the sax player how to make music on the brass instrument. Without any need to play the trombone, the musician might stick with the instrument familiar to her. With enough motivation, such as playing in a high-paying wedding, the sax player is likely to retrain herself on the new instrument. Balázsi is seeking to understand how yeast make similar kinds of genetic changes to survive during drug treatment.

A physicist by training, Balázsi feels driven by the desire to make models that can make predictions. He hopes these kinds of experiments can find an application in the ongoing battle with drug resistance and diseases.

“His physics background provides him with a larger scale systems view of what’s happening,” said James Collins, a professor in the Department of Biological Engineering at the Massachusetts Institute of Technology. “He’s one of the pioneers at introducing network approaches into biology.”

Collins and Balázsi worked together when Balázsi was a postdoctoral researcher. The two researchers recently discussed beginning a collaboration using network biology on tuberculosis.

Working with yeast makes it possible to make the kinds of evolutionary predictions and conduct experiments that would be considerably more difficult with animals. With yeast, he can observe as many as 80 generations within 10 days because yeast divide eight to 10 times in the lab. Observing genetic changes in response to environmental conditions over a few weeks with yeast would be like traveling through centuries with animals or millennia with humans.

Last year, Balázsi completed a five-year grant from the National Institutes of Health through the Director’s Program.

While Balázsi is continuing to work with yeast cells, he is now also pursuing research on cancer. He has been working to introduce multiple synthetic gene circuits into cancer, similar to what he did with yeast, aiming to control cancer cells and understand their biology.

A native of Transylvania, a region that is now part of Romania, Balázsi grew up speaking Hungarian and studied Romanian in school. He came to the United States in 1997. He and his wife Erika live in East Setauket with their daughter Julianna. The Balázsi family moved to Long Island last summer.

Balázsi enjoys traveling to New York City and New Jersey, where he and his wife enjoy taking part in traditional Hungarian folk dancing.

The kind of experiments Balázsi has done and would like to continue to do may one day give scientists the ability to anticipate how a cancer or drug-resistant strain of a disease might react to a new treatment.

“If we are clever enough and we design a gene circuit that lures the cells into an evolutionary trap, where they evolve in a certain way that later on becomes disadvantageous, we could possibly help cure” these diseases, he said. This kind of approach and solution, however, is “far away” from the basic knowledge researchers now have because scientists don’t yet understand enough about the evolution of cancer cell populations in humans.

Look, up in the sky! It’s a bird, it’s a plane, it’s … phytoplankton? Parts of tiny creatures that live on the top layer of the oceans, and the stuff they excrete, get carried into the air when bubbles at the surface burst and waves break on top of them. These airborne particles help form ice clouds.

In large parts of the Southern Ocean, the North Atlantic and the North Pacific, sea spray aerosol containing this marine biogenic material can represent a source of ice-forming particles.

While researchers had known that parts of these microorganisms could become freed from their water environment and rise into the air, they didn’t realize the extent to which so-called exudate material, which is secreted or released by phytoplankton into the water, could also become a part of ice clouds. This includes excess material from phytoplankton photosynthesis, waste material and other secretions.

“We found the ice forming material in the ocean microlayer and can attribute it to material produced by photoplankton,” said Daniel Knopf, an associate professor at the Institute for Terrestrial and Planetary Atmospheres at Stony Brook’s School of Marine and Atmospheric Sciences.

Indeed, Lynn Russell, a professor of Climate, Atmospheric Science and Physical Oceanography at Scripps Institution of Oceanography, described these results, which were recently published in the journal Nature, as a “big step.”

“It’s an interesting finding,” Russell said. “This shows that [other] organic material” can contribute to the formation of ice clouds.

Josephine Aller, a professor at the School of Marine and Atmospheric Sciences, said understanding the role of phytoplankton in the atmosphere could offer a better awareness of how any changes that affect phytoplankton, such as an increase in carbon dioxide or a rise in temperature, might also change the formation of clouds.

The Stony Brook researchers combined field work, which included a northwest Atlantic cruise, and lab work performed at Stony Brook and at the Advanced Light Source at Lawrence Berkeley National Laboratory. The Stony Brook team probed microlayer film to determine its spectroscopic, or chemical, signature. They discovered the controlled experiments produced particles that were similar to the ones in the field.

Finding the same material in the lab that they observed in nature was “like a rocket launch,” said Knopf. “For me, I thought, ‘Wow, this half millimeter thick ocean surface may affect a cloud at ten kilometers in height.’ How incredible is that?”

Over oceans, where dust and inorganic materials are scarce, ice clouds can form around these phytoplankton parts.

Some studies over the last few years suggest that ocean acidification is likely to impact biological processes in ocean surface waters and modify the nature and production of organic matter, Aller said. If this happens, there may be an effect on material that is transferred from the surface to the atmosphere, with the greatest effect likely occurring in polar regions.

Scientists don’t yet have enough of the big picture, such as a vertical distribution and numbers of particles and a physical description of how ice forms depending on temperature and relative humidity, to feed this information into global climate models, Knopf said.

To gather more information about clouds and the particles that make them up, researchers have used converted spy planes that take 20 minutes to reach their target altitude and can collect data for about seven hours.

“The pilot has to be like an astronaut in a space suit,” Knopf said. “Our knowledge is a bit limited” due to the limited sampling opportunities.

While scientists know that thunderstorm clouds have a cooling effect, while others, such as cirrus clouds, have a warming effect, they can’t always predict the type of clouds that will form under different conditions. The specific cloud type depends on the particle involved, Knopf said.

Still, the two scientists, who have worked together for seven years, said they will continue collecting this kind of information which, one day, may offer a greater understanding of how a changing ocean might impact phytoplankton growth and potentially the release of airborne particles.

A resident of Huntington, who is originally from Germany, Knopf and his wife, Jeong-A Seong, have a primary school daughter. Aller, meanwhile, lives in Stony Brook with her husband, Robert Aller, a distinguished professor at the School of Marine and Atmospheric Sciences. The couple have four adult children.

As a trained physicist, Knopf said he appreciates how his awareness of phytoplankton’s role in the atmosphere can inform what he sees.

“I go to the beaches on Long Island and I see the film and I sometimes think, ‘maybe this thing, in two weeks, is … making ice crystals,’” Knopf said. Under the right conditions “it could come back as a raindrop.”

Luisa Escobar-Hoyos found, checked and rechecked something so remarkable that she wanted to share it. Her work, which had taken two and a half years to complete, had defied conventional wisdom when she discovered the unexpected role of an enemy most thought of as a bystander in the cancer battle.

When she and her lab director, Dr. Kenneth Shroyer, head of the Department of Pharmacology  at Stony Brook University, sent the paper off to publications to share what they’d learned, they received almost immediate rejections.

“We knew we had a good story,” Escobar-Hoyos recalled, “and we kept pursuing it.”

Indeed, Escobar-Hoyos and Shroyer submitted their results to Cancer Research, where they published their findings in the Sept. 1 issue.

Escobar-Hoyos focused on keratin 17, which is a part of a class of 54 proteins in the keratin family. Keratin 17 is not normally present in mature epithelia. It is expressed during embryologic development and in some immature cell types, including stem cells within normal hair follicles and in nail beds and in cells that are putative stem cells within the cervical mucosa, Shroyer said.

Scientists had long considered keratin 17 to play a supportive structural role, serving like a tent pole outside the cell, away from the genetic machinery in the nucleus that acts as a controller for the cell’s fate.

As it turns out, however, this protein, which is normally in the off state, can become a party crasher in cancer cells in the nucleus, entering this critical region and dragging the tumor suppressor protein p27 into the cytoplasm, where it is degraded. This action disrupts the work of a regulator of organized cell division and growth.

Yusuf Hannun, the director of the Cancer Center at Stony Brook University, called this a “very exciting development” and suggested this was a “surprising role” for keratin 17, which is “likely to be a key player in the pathogenesis of cancer.”

Scientists generally believed keratins provided structural and mechanical support within the cytoplasm. Another group of researchers, led by Pierre Coulombe at Johns Hopkins University, discovered that nuclear K17 can regulate gene expression in skin cancer cells. Nature Genetics accepted Coulombe’s paper less than a month after the work of Shroyer and Escobar-Hoyos, and provided “important cross-validation of our discovery that nuclear K17 can impact the biologic properties of cancer cells.”

The only one of the class of keratins that Shroyer is aware has the ability to enter the nucleus, keratin 17 somehow becomes more abundant in some forms of cancer.

“We suspect that there is a molecular switch or other molecular events that turn on the expression of K17,” Shroyer said. “We have not yet explored all the potential actions that K17 may have, once it enters the nucleus.”

Led by Danielle Fassler, an M.D./Ph.D. student, Shroyer’s lab is studying what increases productions of this protein.

Shroyer and Escobar-Hoyos are also looking for ways to inhibit K17 function inside the nucleus. Based on the research conducted by Shroyer and Escobar-Hoyos, Stony Brook has recently signed a licensing agreement with OncoGenesis, a biotechnology company that plans to use K17 as a diagnostic marker rather than a therapeutic target.

The company plans to incorporate it in a panel for a new cervical cancer screening device. The scientific duo will give three talks at an upcoming human papilloma virus meeting in Lisbon, Portugal.

Shroyer is inspired by the results in the paper and by the determination of Escobar-Hoyos, a Fulbright Scholarship winner who will complete her Ph.D. thesis in November and will begin a postdoctoral research program at Memorial Sloan Kettering next February.

“It’s definitely the most complex paper that has ever come out of my lab,” Shroyer said.

“The fact that she was able to track down with such precision exactly how K17 targets p27 was really extraordinary.”

Shroyer and Escobar-Hoyos will continue to work together after she completes her Ph.D. Escobar-Hoyos is training Fassler to do some of the work. She also plans to come to Stony Brook at least once a month and potentially more than that.

“I have seen [Escobar-Hoyos] present her work and we are all very proud of her,” added Hannun.

Escobar-Hoyos, who lives in Riverhead, said she feels at home on Long Island, where she and her husband Nicolas Hernandez, who was also a Fulbright scholar, go kayaking on Peconic Lake.

When she was in college in Colombia, Escobar-Hoyos knew she wanted to become a scientist. She also knew she wanted to study cancer and, once she started her graduate career, perform research that might have a clinical benefit.

“I wanted to have a role as a young scientist in this disease,” she said. “Now, I want to understand it and be able to diagnose it earlier and cure it.”

When she conducted her research on K17, she knew she had to overcome some resistance.

“People would disregard keratins” in the nucleus because “they are so sticky,” she said. “They wanted to focus on the other, more interesting parts.”

Escobar-Hoyos appreciated the consistent help from Shroyer and said Shroyer was “always supportive as a mentor.”