Insects, Bacteria & Ice

Valeria Molinero

Contrary to what you may have been taught, water doesn’t always freeze to ice at 32 degrees F (zero degrees C). Knowing, or controlling, at what temperature water will freeze (starting with a process called nucleation) is critically important to answering questions such as whether or not there will be enough snow on the ski slopes or whether or not it will rain tomorrow.

Nature has come up with ways to control the formation of ice, though, and in a paper published in the Journal of the American Chemical Society University of Utah professor Valeria Molinero and her colleagues show how key proteins produced in bacteria and insects can either promote or inhibit the formation of ice, based on their length and their ability to team up to form large ice-binding surfaces. The results have wide application, particularly in understanding precipitation in clouds.

“We’re now able to predict the temperature at which the bacterium is going to nucleate ice depending on how many ice-nucleating proteins it has,” Molinero says, “and we’re able to predict the temperature at which the antifreeze proteins, which are very small and typically don’t work at very low temperatures, can nucleate ice.”

What is ice nucleation?
It’s long been known that life likes to mess with ice. Insects, fish and plants all produce various forms of antifreeze proteins to help them survive in below-freezing conditions. And plant pathogens, particularly the bacterium Pseudomonas syringae, employ proteins that promote the formation of ice to induce damage in their hosts. Before we can talk about how these proteins work, though, we need a quick refresher on how ice freezes.

Pure water, with no impurities, won’t freeze until it reaches -35 degrees C (-31 degrees F). That’s the temperature at which the water molecules will spontaneously arrange into a crystal lattice and start to recruit other molecules to join in. To start the freezing process at warmer temperatures, however, water molecules need something to hold on to, like a speck of dust, soot or other impurity, on which it can start building its crystal lattice. This is the process called nucleation.

Ice-nucleating proteins, such as those in Ps. syringae, bind to nascent ice crystallites in such a way as to reduce the energy cost of additional freezing. They can also aggregate together to further enhance their nucleating power. “It is a lot of group work!” Molinero says.

These proteins can be so efficient that they can nucleate ice at temperatures as warm as -2 degrees C (29 degrees F). Ice-nucleating proteins are already being put to use at ski resorts, with Colorado-based Snomax International marketing an additive containing Ps. syringae that gives snowmaking machines a boost.

Antifreeze proteins, however, also bind to ice, but force it to develop a curved surface that discourages additional freezing and requires much colder temperatures for ice to grow. Also, antifreeze proteins don’t aggregate together. “They have evolved to be loners, as their job is to find ice and stick to it,” Molinero says.

All of this was previously known, including the fact that antifreeze proteins were relatively small and ice-nucleating proteins were relatively large. What wasn’t known, though, was how the sizes and aggregating behaviors of the proteins affected the temperature of ice nucleation. That’s the question Molinero and her team set out to answer.

A “single bullet”
Molinero and graduate students Yuqing Qiu and Arpa Hudait conducted molecular simulations of protein interactions with water molecules to see how they affected the temperature of ice nucleation. Antifreeze and ice-nucleating proteins, Molinero says, bind to ice with nearly equal strength.

“Nature is using a single bullet in terms of interactions to address two completely different problems,” she says. “And the way it has resolved between antifreeze or ice nucleation is by changing the size of the proteins and their ability to team up to form larger ice-binding surfaces.”

Antifreeze proteins, they found, nucleated at just above -35 degrees C, which matched experimental data. Lengthening the simulated proteins increased the nucleation temperature, which plateaued after a certain length. The simulations predicted that further assembling around 35 bacterial proteins into larger domains was key to reach the ice-nucleating performance of Ps. syringae, with a nucleation temperature of -2 degrees C (29 degrees F).

“Now we can design new proteins or synthetic materials that nucleate ice at a specific temperature,” Molinero says.

Why it matters
The implications of such a finding extend all the way to the future of water on Earth.

Precipitation begins as ice, which nucleates and grows until it’s heavy enough to precipitate. At high altitudes where it’s colder, soot and dust can do the job of triggering nucleation. But at lower altitudes, it’s not dust that triggers nucleation—it’s bacteria.

Yes, the same proteins in Ps. syringae that aid snowmaking at ski resorts also aid ice formation at warmer temperatures, allowing low-altitude clouds to precipitate. In a warming climate, Molinero’s findings can help climate modelers better understand the conditions of cloud formation and precipitation and forecast how warming will affect the amount of ice nucleation and precipitation in the future.

“The ability to predict whether the clouds are going to freeze or not is super important in climate models, because ice formation determines precipitation and also the ratio of solar energy absorbed and reflected by our atmosphere,” Molinero says. “The challenge to predict whether ice is going to nucleate or not in clouds is a major limitation the predictive ability of weather and climate models.”

At a much smaller scale, however, the antifreeze and ice-nucleating proteins can be employed together in a fine-tuned ice dance: Some insects use antifreeze proteins to protect themselves down to around -8 degrees C (18 degrees F), but then employ ice-nucleating proteins at lower temperatures to contain ice growth before it gets out of hand.

“The big picture is that we now understand how proteins use their size and aggregation to modulate how much they can nucleate ice,” Molinero says. “I think that this is quite powerful.”

AMS Fellow

“It’s such an honor to be selected to join the American Mathematical Society,” said de Fernex, professor and associate chair of the department. “It’s also gratifying to have my work recognized by my peers for contributing to the profession.”

As a child and throughout his school days, de Fernex always enjoyed math. At the University of Milan, he studied math in the morning and worked as an illustrator at an advertising agency in the afternoon. For a time, he gave up studying math and switched to architecture. “It was while studying architecture that I began to realize my true passion for math,” said de Fernex. “I was on a train to Venice with some friends when it hit me. They were majoring in math and telling me about the things they were learning. In that moment I realized how much I missed it.” He left architecture and advertising and began to see himself as a mathematician.

He completed his undergraduate degree and wrote a dissertation in the field of algebraic geometry. “What I like about algebraic geometry is the balance between intuition and mathematical rigor,” said de Fernex. “The algebraic part of it provides a powerful and rigid structure, which, paradoxically, gives geometry its flexibility.” Algebraic geometry has applications in many fields—for example, certain topics, such as Calabi-Yau manifolds, are important in string theory because they meet the supersymmetry requirement for the six “unseen” spatial dimensions of string theory.

He began working on his Ph.D. at the University of Genoa but later moved to the U.S. to complete his studies at the University of Illinois at Chicago. The importance of his work was recognized early on, and his research has been well-funded throughout his career. He has received various fellowships as well as support from the National Science Foundation (NSF) and the Simons Foundation. “The funding I received from the U’s John E. and Marva M. Warnock Presidential Chair in Mathematics and the NSF Career grant were especially helpful,” said de Fernex. “They funded my research and provided support for grad students and postdocs. The years supported by the NSF at the Institute for Advanced Study and later by the Simons Fellowship in my sabbatical year allowed me to fully focus on research and collaboration for extended periods of time.”

While de Fernex enjoys doing research, he is equally enthusiastic about teaching. “You never know where or when you’ll find talented students,” he said. “That’s what keeps teaching exciting and fulfilling.”

AMS Fellow

“I was delighted to learn the news from the AMS,” said Trapa, professor and former chair of the Mathematics Department and currently chair of the Physics & Astronomy Department. “I’m grateful to be recognized in this way.”

Trapa has always been fascinated by mathematics, but his interests drifted as an undergraduate at Northwestern University, first to chemistry, then to physics, before finally returning to mathematics. “I realized that the common thread that I enjoyed most about the basic sciences was the underlying math.” Trapa also credits two a couple of math professors—Michael Stein, emeritus professor, and the late Mark Pinsky—who took him under their wing and “really changed the trajectory of my career.”

After a brief stint doing statistical analysis for the Ford Motor Company, Trapa headed to MIT for his Ph.D. “My time at Ford was a lot of fun, but not for the reasons that my bosses would have liked,” Trapa said, adding that the company had a decent mathematics library where he spent most of his time. At MIT, Trapa studied representation theory with David Vogan, Norbert Wiener Professor of Mathematics. Vogan later became a close friend and collaborator. “Working with David has been one of the great honors of my life. I’m constantly learning from him how to be a better mathematician.”

Trapa held postdoctoral appointments at the Institute for Advanced Study at Princeton and at Harvard before joining the faculty at the U in 2001. His most important contributions involve classifying the kinds of symmetry that can appear in physical and mathematical problems, so-called unitary representations of reductive Lie groups. “In the past few years, there have been some beautiful and unexpected developments in the subject that lead in many new directions,” Trapa said. His work in this area has been supported by grants from the National Science Foundation, the National Security Agency, and the Simons Foundation. Since 2015, Trapa has served as managing editor for the AMS journal Representation Theory.

Outside of his research, Trapa enjoys working with talented students of mathematics. He helped found the Utah Math Circle for high school students, served as its director for many years, and still lectures regularly in it. “The kind of math that students learn in school is often very different from the experience of actually doing mathematics,” Trapa said. “I think it’s important to give young kids a taste of what mathematics is all about.”

Plant Genomics

QUESTION:

How does RNA decay contribute to gene expression? Could the RNA decay rate be regulated on a molecular basis in order to control genetic traits?

Gene expression is typically measured as messenger RNA (mRNA) abundance, and changes in that abundance are usually attributed to transcription, or synthesis, of mRNA inside the cell. However,
RNA abundance is also influenced by its disposal, or degradation, but how degradation controls RNA abundance is not well understood.

WHO:

“My research uses a plant model, Arabidopsis thaliana, a small mustard plant, and we found that mutants with defects in mRNA decapping proteins experienced abnormal cell growth,” says Leslie Sieburth, Professor of Biological Sciences at the U.

“Our curiosity about why the mutants showed such poor growth led us to discover another mRNA decay enzyme, which we call SOV. We noted in our publication, in 2010, that most eukaryotic genomes encode a very similar protein, including humans,” says Sieburth.

A few years later, in 2013, scientists studying a human disorder called Perlman syndrome discovered that it was caused by mutations in the same gene. The gene, SOV, is known as DIS3L2 in humans.

Perlman syndrome is a genetic disorder associated with overgrowth in the size of the body or a body part of infants. The condition is almost always fatal prior to birth. The disorder has been grouped with Renal cell carcinoma and an increased risk for Wilms tumor.

Starting in 2014, Sieburth investigated how mRNA decapping and SOV/DIS3L2 contribute to decay of all mRNAs using genome-wide approaches.

“A fruitful collaboration with Fred Adler, a professor of biology and mathematics at the U, one of his graduate students, Katrina Johnson, and my postdoc Reed Sorenson, identified the decay rates of more than 17,000 mRNAs, and the contributions from decapping and SOV/DIS3L2,” says Sieburth.

One unexpected discovery was that the mRNAs that decay the fastest use the mRNA decapping pathway. A second discovery was that Arabidopsis mutants lacking an active SOV initiate a feedback pathway where the mRNAs – that are normally degraded by SOV – switch decay pathways, decay faster, and are also transcribed faster.

The results were published in Proceedings of the National Academy of Sciences (PNAS) in 2018.

FUNDING:

Research in the Sieburth laboratory is supported by four National Science Foundation (NSF) grants totaling nearly $2 million. The largest grant, titled, “The role of regulated degradation in controlling cytoplasmic mRNA levels,” focuses on mRNA decay pathways and enzymes, such as SOV. The funding will extend to 2020.

Sieburth recently received a new award funded through NSF’s Early-concept Grants for Exploratory Research (EAGER) program for her project, “Connecting RNA Molecular Kinetics to Developmental Regulation.”

Sieburth employs two undergraduate students, two graduate students – Alex Cummins and
Jessica Vincent – and one postdoctoral fellow, Reed Sorenson.

IMPACT:

Sieburth’s continuing genetic studies could provide new perspectives to fundamental cellular processes that are important in cancer biology and birth defects in humans.

In addition to research, Sieburth also is implementing new curriculum in the School of Biological Sciences. She is currently teaching a new class designed specifically for first-year students. The course, Fundamentals of Biology, is one part of a class sequence that includes two lecture-type classes and two laboratory classes.

“I led a curriculum reform committee, and along with nearly everyone in the School, have spent the past two years designing these courses, reading the literature to identify the instructional methods that have proven to lead to deep learning, and pulling together instructional materials,” says Sieburth. “We are a few months into the class now, and it is exciting to see that the students are engaged and learning.”

FUTURE:

Sieburth has three specific goals for the current NSF study, “The role of regulated degradation in controlling cytoplasmic mRNA levels.”

The first is to assess changes in mRNA decay rates in response to conditions where RNA abundance changes. Usually abundance changes are attributed to transcription, but few scientists have tested the contributions from RNA decay.

The second goal is to understand the feedback that occurs in SOV mutants in Arabidopsis.

Third, she wants to understand the basis for the wide range in mRNA decay rates, where half-life varies between 3.5 minutes and more than 24 hours.

Breakthrough Prize

Christopher Hacon, distinguished professor of mathematics at the U, has been interested in math for as long as he can remember. As a child, he loved playing with numbers and would spend hours on a calculator trying to count and figure out things—such as how much all the books in his house cost, or the number of seconds in a year or a lifetime. He particularly enjoyed figuring out patterns and seeing the relationships among numbers.

When he got to college, Hacon thought he would study physics and engineering, but when he was accepted into a prestigious math program, he ran with it and never looked back.

Awards and Recognition

Today Hacon has carved out a career as one of the world’s top mathematicians and has been recognized with numerous awards for teaching and research. In December 2017, he was awarded a 2018 Breakthrough Prize in mathematics at a star-studded event in Silicon Valley. The $3M Breakthrough Prize recognizes achievements in fundamental physics, life sciences, and mathematics and is one of the most generous prizes given in science. Hacon shares the award with his collaborator and colleague, James McKernan, professor of mathematics at the University of California San Diego.

In 2018, Hacon was elected to the National Academy of Sciences, and in 2019, he was elected Fellow of the Royal Society of London. He was recently named the first recipient of the McMinn Presidential Endowed Chair in Mathematics at the U.

Hacon’s research is in algebraic geometry, the field that studies geometric objects defined by polynomial equations. Algebraic geometry connects and elevates algebra, which solves polynomial equations, and geometry, which describes the shapes that arise from those equations.

“I am extremely honored and humbled to receive the Breakthrough Prize and to be awarded the McMinn Chair,” said Hacon. “The work I've done and am doing is the culmination of sustained efforts by many brilliant mathematicians. It is very exciting that the field of birational algebraic geometry and the University of Utah are receiving this kind of recognition.”

Early Life in Italy

Hacon was born in England but moved with his parents to Italy when he was three. His father was a mathematician, too, and served as a postdoctoral scholar in the math department at the University of Pisa. Hacon graduated from the same university and then moved to the United States at age 23 to pursue a Ph.D. in mathematics at the University of California Los Angeles.

“Italy was a great place to grow up, and I visit when I can,” he said. “Unfortunately, it’s never as often as I’d like.”

He arrived at the U as a postdoctoral scholar in 1998 and returned as a professor in 2002.

“One of the things I love about math is that it allows me to find patterns and explain the reasons behind a certain behavior,” said Hacon. “This is really the essence of scientific discovery. All of these patterns are described by numbers. I’m fascinated by them, regardless of their origin. I’m constantly surprised by the power of math and abstract thought in general. It is truly amazing to read a mathematical proof dating back decades or centuries, which is still correct and interesting—both today and in the future.”

Mentors and Teaching

Hacon credits his mentors with providing inspiration and helping him move forward in his career. “While I have been inspired by many people, I have four mentors who have really made a difference in my life. They are Fabrizio Catanese and Fabio Bardelli at the University of Pisa, Robert Lazarsfeld at UCLA, and János Kollár, my postdoctoral advisor at the University of Utah, who now teaches at Princeton.”

Hacon enjoys teaching students at the U and finds the Department of Mathematics is a good place to work. He and his wife, Aleksandra Jovanovic-Hacon, who is a math instructor at the U, are busy raising their six children. They like the outdoors, especially rock climbing, hiking, and skiing.

“Working as a mathematician has been great,” said Hacon. “The academic freedom to pursue my own research goals is one of the biggest rewards I have, as well as working with students and other researchers.”

Hacon hopes to continue his research, while inspiring the next generation of mathematicians. He would love to see his students surpass his efforts and continue to make strides in further exploring and expanding our understanding of algebraic geometry.

 

> first published in Aftermath - 2018

Under Pressure

Scientists have solved decades long puzzle about lithium, an essential metal in cellphone and computer batteries. Using extreme pressure experiments and powerful supercomputing, the international team has unraveled the mystery of a fundamental property of lithium. Its atoms are arranged in a simple structure, and may be the first direct evidence of a quantum solid behavior in a metal.

Until now, all previous experiments have indicated that lithium’s atoms had a complex arrangement. The idea baffled theoretical physicists. With only three electrons, lithium is the lightest, simplest metal on the periodic table and should have a simple structure to match.

The new study combined theory and experimentation to discover the true structure of lithium at cold temperatures, in its lowest energy state.

Scientists suggest that rapid cooling led lithium atoms to arrange themselves in complex structure and resulted in misinterpretation of the previous experimental results. To avoid this, Shanti Deemyad, associate professor at the University of Utah who led the experimental aspect of the study, applied extreme pressure to the lithium before cooling down the samples.

Deemyad’s research group prepared the lithium samples in tiny pressure cells at the U. The group then traveled to Argonne National Laboratory to apply pressure up to 10,000 times the Earth’s atmosphere by pressing the sample between the tip of two diamonds. They then cooled and depressurized the samples, and examined the structures at low pressure and temperature using X-ray beams.

The researchers looked at two isotopes of lithium — the lighter lithium 6 and heavier lithium 7. They found that the lighter isotope behaves differently in its transitions to lower energy structures under certain thermodynamic paths than the heavier isotope, a behavior previously only seen in helium. The difference means that depending on the weight of the nuclei, there are different ways to get to the lower energy states. This is a quantum solid characteristic.

Graeme Ackland, professor from the University of Edinburgh, led the theoretical aspect of the study by running the most sophisticated calculations of lithium’s structure to date, using advanced quantum mechanics on the ARCHER supercomputer. Both experimentation and theoretical parts of the study found that lithium’s lowest energy structure is not complex or disordered, as previous results had suggested. Instead, its atoms are arranged simply, like oranges in a box.

The study, from the Universities of Edinburgh and Utah, was published in Science.

Corresponding author Deemyad of the University of Utah Department of Physics & Astronomy, said: “Our experiments revealed that lithium is the first metallic element with quantum lattice structure behavior at moderate pressures. This will open up new possibilities for rich physics.”

Co-author Miguel Martinez-Canales of the University of Edinburgh School of Physics and Astronomy, said: “Our calculations needed an accuracy of one in 10 million, and would have taken over 40 years on a normal computer.”

Lead theoretical author Graeme Ackland of the University of Edinburgh School of Physics and Astronomy, said: “We were able to form a true picture of cold lithium by making it using high pressures. Rather than forming a complex structure, it has the simplest arrangement that there can be in nature.”

Adapted from University of Edinburgh release: http://www.ed.ac.uk/news/2017/piling-on-pressure-solves-mystery-about-metal