Volume 3, Issue 23 October 2006
Revealing the Invisible of the Universe
Theoretical physicist Hitoshi Murayama at work. (From "Discovering the Quantum Universe: The Role of Particle Colliders," 2006. DOE/NSF High Energy Physics Advisory Panel.)
The questions "Why are we here?" and "Why do we exist?" may sound purely philosophical in nature. Scientists, however, believe answers to these questions lie in the sub-atomic world inhabited by quarks and neutrinos. These fundamental particles were created when the universe was formed and, to theoretical physicists like UC Berkeley's Hitoshi Murayama, they represent clues to life's ultimate mysteries.
"Once you know how these tiny particles work, you can answer how the universe came about," says Hitoshi Murayama, professor in the Department of Physics. According to the laws of physics, our existence would not be possible without some process that was able to create and exploit a minute imbalance in energy. "That little bit of energy is why we are here," says Murayama, who is also a member of the Berkeley Center for Theoretical Physics (BCTP).
Murayama and others believe neutrinos may hold the key to this process and that they played an important role in the evolution of the universe. Neutrinos are produced by radioactive decay, including that generated by nuclear power plants, the sun and exploding stars. Trillions of these invisible, electrically neutral particles pass through the human body every second. For many years, scientists believed neutrinos were weightless entities moving at the speed of light.
In 1998, scientists discovered that neutrinos had a small, but finite mass. The discovery overturned an orderly and elegant view of the universe called the Standard Model, which had held up to more than 30 years' worth of scientific challenge. Now, Murayama and his colleagues have taken on the task of re-thinking the Standard Model in light of the discovery of neutrino mass.
As a theoretical physicist, Murayama works to construct a model that would explain experimental observations of the physical world. These models help make sense of previous research and serve to guide future experiments. The importance of this theoretical work is highlighted by the history of the discovery of neutrinos. Nobel Laureate Wolfgang Pauli first hypothesized their existence in 1930. Scientists did not confirm his theory until 1956. Today, neutrinos are the focus of intense, worldwide scientific scrutiny.
Murayama, for example, is part of an international team of scientists conducting experiments aimed at revealing the fundamental properties of neutrinos. Because they are nearly weightless and electrically neutral, they often pass through the earth without interacting with any atoms. This makes observing them incredibly challenging. "However, once in a while, neutrinos leave traces of themselves behind," Murayama explains.
The history of the universe as seen by particle physicists, beginning with the Big Bang and showing various particles and their relative distribution through to present time. (Courtesy of the Particle Data Group, Lawrence Berkeley National Lab)
In order to observe and capture data on these rare sub-atomic interactions, a multi-national consortium built a neutrino observatory, called KamLAND, beneath an abandoned zinc mine near Kamioka, Japan. (KamLAND stands for Kamioka Liquid-Scintillator Anti-Neutrino Detector.) The observatory consists of a sphere 42 feet in diameter filled with mineral oil located 1 kilometer below the earth.
A flash of light is produced when neutrinos collide with hydrogen protons within the oil. Scientists record these interactions for later study. Murayama travels to Japan once a year to take a shift monitoring the activity within the sphere. The experiment is painstaking work, he says. About only one neutrino-proton collision is recorded per day.
While he is studying the role of neutrinos in the sub-atomic world, Murayama is also studying their place in the universe. Scientists believe there are five thousand neutrinos in every cubic inch of the universe, billion times more than ordinary atoms. "With so many of them, they must have played important role in the birth and evolution of the Universe," Murayama says. Neutrinos are an important part of the "dark side" of the universe, namely 95 percent of the energy of the universe that is not atoms and cannot be seen in telescopes.
Today, Murayama and others continue to design and test models that attempt to encompass all scientific observations of the physical world, the so-called Unified Theory. Murayama is among those eagerly awaiting data generated from experiments to be done at two international facilities, the Large Hadron Collider (LHC), nearing completion and the International Linear Collider (ILC), in planning. LHC and ILC experiments aim to produce dark matter for the first time in the lab, as well as conduct the most detailed studies of the sub-atomic world to date. The data promise to give scientists what they need to finally come up with a Unified Theory that stands the test of time. "We are literally on the verge of better understanding of our place in the universe," Murayama says.
Related Web Sites
Unraveling Plant Ancestry Through Modern Technology
Baldwin at work in Carson Ridge, Marin County. In addition to his research using plant DNA, Baldwin is editing a new edition of the Jepson Manual, an extensive guide to California's native and naturalized plants. (Photo by Bridget Wessa)
Since Swedish botanist Carl Linnaeus created the modern biological classification system in the mid 18th century, botanists have determined a plant's place among the wild diversity of life on the planet primarily based on its morphology, or form.
But to Bruce Baldwin, a professor of integrative biology at UC Berkeley, what a plant looks like isn't always the best indicator of its species or closest relatives. "When morphological similarity has been the sole line of evidence, it's often been misleading about evolutionary relationships," he says.
Baldwin, whose specialty is native plants of California and the Hawaiian plants that evolved from them, uses DNA testing to resolve plants' ancestry and evolution. The evidence he has unearthed shows that plant evolution can occur more rapidly than once thought, and that plants evolve with remarkable precision to fit sometimes extremely local environments. While botanists have long known that California is rich in native species, Baldwin and his students' work proves that the state's plant life is even more varied and diverse than his predecessors imagined.
Baldwin's most extensive studies have focused on Madiinae, a group of plants in the sunflower family commonly known as tarweeds. The group includes plants that look dramatically different from one another, from the more than 6-feet tall, yucca-like Hawaiian silversword to the tiny California tarweed, Hemizonella minima, often less than an inch in height. "The group has undergone tremendous change for having such a short evolutionary history," says Baldwin.
Baldwin, who is also the curator of the Jepson Herbarium at UC Berkeley, has recently used experimental and genetic methods to explore theories about the evolution of different tarweed species proposed by earlier researchers, including Jens Clausen, David Keck, and William Hiesey, a Bay Area team well known worldwide in botanical circles. The three were pioneers at their time, from the 1930s to 1950s, for incorporating genetics, ecology, and physiology into plant classification. But they lacked the tools necessary to resolve relationships with modern levels of precision.
A rare, yellow variety of Layia glandulosa. The yellow variety is more closely related to L. discoidea than it is to the white plants of its own species. (Photo by Br. Alfred Brousseau, Saint Mary's College)
"There wasn't at that time a way to reconstruct genealogies rigorously, and there certainly wasn't any means of getting at the actual timing of when one species separated from another," says Baldwin.
To determine relationships between different plant species or populations, Baldwin extracts their DNA, then sequences non-coding regions that evolve rapidly enough to provide evidence of recent evolutionary change. Instead of looking for overall genetic similarity between species as in the past, which can be misleading, Baldwin reconstructs relationships based on the fewest mutational steps, or a more explicit model of DNA sequence evolution.
Through these and other techniques, he's been able to resolve questions left unanswered by earlier botanists. One of these questions is the evolutionary history of Layia discoidea ("Discoidea"), also known as rayless layia, a small annual herb.
Unlike other layias, Discoidea has a yellow bloom without rays, or showy petal-like flowers. It lives in serpentine soils, with a mineral composition toxic to many plants, in a small area of San Benito and Fresno counties, and looks so different from other tarweeds that some botanists once thought it wasn't even a member of the tribe.
Layia discoidea, a plant whose evolutionary history had long baffled botanists. (Photo credit: James R. Griffin/California Native Plant Society)
Clausen's team discovered it was a tarweed and related to Layia glandulosa ("Glandulosa"), or white layia, a ray-bearing plant found in sandy soils throughout the western United States. But the researchers weren't sure which plant came first, and thought that the rayless plant could be an evolutionary relict.
Through genetic testing, Baldwin found that Discoidea split from Glandulosa less than a million years ago. And he discovered an interesting fact about both species. Glandulosa's common name – white layia – is something of a misnomer. While most of the plants have white rays, a rare variety has yellow rays. Baldwin discovered that the rare, yellow-rayed version is more closely related to Discoidea, a separate species, than it is to the white-rayed plants in its own species. That means Discoidea underwent such rapid change that its close relationship to yellow Glandulosa was obscured, except with the aid of molecular data, Baldwin explains. Discoidea even retains a gene coding for yellow ray color, although it no longer has rays, he says.
This example "shows that evolution can proceed at very different rates and in very different ways, depending on ecological circumstances," Baldwin says. California, with its many microclimates and soils, offers a multitude of distinct environments that have shaped plant evolution here, Baldwin says. That means the state likely has many new species yet to be discovered, he adds.
But Baldwin knows if species lose their habitats, they could disappear before being discovered. "If a (species) disappears, we're losing something irreplaceable," he says. "We still aren't knowledgeable enough to say whether these plants have special ecological properties or special medicinal properties," he adds. "But we do know once they're gone, they're gone forever."
Related Web Sites
Ironing Out Bacterial Infections
Kenneth Raymond works on iron-chelating siderophore molecules with graduate students Rebecca Abergel (left) and Trisha Hoette (center). (Courtesy the Raymond Lab)
From the moment bacteria invade a human cell, they launch a battle against the body to acquire iron. Like humans, bacteria need this mineral to make energy and replicate their genes. Though iron is the second-most abundant metal on Earth, it's in short supply inside cells, where it's bound to the storage proteins transferrin and ferritin.
Pathogenic bacteria have evolved an ingenious way to overcome this problem. By sending out small iron-chelating molecules known as siderophores, bacteria can literally wrest iron away from storage proteins. Many siderophores can bind to iron orders of magnitude more strongly than transferrin and ferritin.
UC Berkeley professor of chemistry Kenneth Raymond has been studying bacterial iron uptake for more than 30 years. It's part of his multifaceted work on coordination chemistry, which ranges from improving MRI contrast agents to devising radioactive waste cleanup methods. This September, the National Institute of Allergy and Infectious Diseases awarded Raymond a $998,325 grant to develop cocktails to treat radiation poisoning by trapping radioactive metal ions.
"I'm interested in how nature transports metals," Raymond says. "I'm interested in siderophores because they are amazingly selective at binding metal ions."
Hundreds of different siderophores have been isolated from dozens of bacterial species living in oceans, soils, and everywhere in between. The rogues' gallery includes some of nature's most deadly pathogens: those responsible for tuberculosis and cholera, salmonella and typhoid fever, bubonic plague and anthrax.
Luckily, humans aren't defenseless in the face of siderophore-bearing bacteria. About five years ago, Roland Strong of the Fred Hutchinson Cancer Research Center in Seattle found that a protein isolated from white blood cells formed ruby red crystals. The crystals' crimson color was a tipoff that they might contain iron. Strong asked Raymond to help determine whether the protein might be involved in thwarting bacterial iron acquisition. The collaboration opened up a fruitful new chapter in immunology.
"Siderocalin is essentially a vacuum cleaner for siderophores. It's the human immune system's response to interrupting bacterial infection," Raymond says. His laboratory is studying all three steps of the siderophore system—the structure of siderophores, the binding behavior of siderocalin, and how bacteria recover iron once it's bound to a siderophore—in hopes of finding ways to foil bacterial iron uptake.
E. coli bacteria use the siderophore enterobactin to steal iron from human proteins such as transferrin. The immune system protein siderocalin can intercept enterobactin, but can't recognize "stealth siderophores" such as aerobactin and salmochelin. (The Raymond Lab)
Raymond is studying why this immune system protein recognizes some siderophores but not others. "If you look at the siderocalin receptor site, it looks like a glove. What is the hand for which this glove was designed?" To probe which characteristics are most important for siderocalin recognition, the researchers are synthesizing natural siderophores with small, custom-made variations. They've found the protein is a generalist that can bind to a wide variety of siderophores a good thing if it's the body's main defense against these molecules.
But the deadliest bacterial strains aren't so easily deterred. To ensure an iron supply, they produce second- or even third-line siderophores. At first glance, these molecules don't seem very formidable; Raymond has found them to be far weaker iron chelators than their first-line cousins. However, "the weaker chelators have the wrong structure to fit into siderocalin. These second chelators are a way to evade the immune system," Raymond says. "This is what I call siderophore stealth."
To determine why siderocalin doesn't bind second-line siderophores, they studied the example of salmochelin. Produced by the bacterium responsible for typhoid fever, it's identical to enterobactin, except that it brandishes big glucose groups on two of its three iron-binding arms. "What this does is make the siderophore too water-soluble and bulky to bind to siderocalin. This glycosylation is another way for the organism to evade the human immune system," Raymond says.
One receptor that binds many types of siderophores helps bacteria recover iron with a novel shuttle mechanism. (from Stintzi et al. Proc. National Academy Science, 2000, 97, 10691-1096)
The third prong in Raymond's research program is determining how bacteria recover iron-siderophore complexes. Already he has discovered that some bacteria use just one general receptor to recognize many siderophores. In this system, the iron-siderophore complex binds to the bacterial receptor and passes the iron to an empty shuttle siderophore, which is what ultimately ferries the metal inside the bacterium. "Iron comes in with a date to the dance, but it never goes into the cell with that date; it always exchanges," Raymond says.
Raymond's discoveries about siderophores have opened up a whole new universe of antibiotic design. Already researchers are developing molecules meant to clog siderophore receptors and essentially starve infecting microbes of iron.
For a decade, Raymond was the only chemist working on siderophores. Today, there is an entire conference devoted to siderocalin alone, attended by dozens of immunologists, biochemists, and chemists. Raymond himself isn't sure where the field is headed. "There have been more twists and turns in this field than an Agatha Christie novel," Raymond says. "If you'd asked me ten years ago whether the human immune system is involved in intercepting iron transport, I'd have said there is no evidence of that. There have been many such surprises over the years I've been working on these compounds; I'm sure I'll see more."
Related Web Sites
Berkeley's Scientific Legacy
Lorem Ipsum
Lorem ipsum dolor sit amet, consectetuer adipiscing elit, sed diam nonummy nibh euismod tincidunt ut laoreet dolore magna aliquam erat volutpat. Ut wisi enim ad minim veniam, quis nostrud exerci tation ullamcorper suscipit lobortis nisl ut aliquip ex ea commodo consequat. Duis autem vel eum iriure dolor in hendrerit in vulputate velit esse molestie consequat, vel illum dolore eu feugiat nulla facilisis at vero eros et accumsan et iusto odio dignissim qui blandit praesent luptatum zzril delenit augue duis dolore te feugait nulla facilisi.
Lorem ipsum dolor sit amet, consectetuer adipiscing elit, sed diam nonummy nibh euismod tincidunt ut laoreet dolore magna aliquam erat volutpat. Ut wisi enim ad minim veniam, quis nostrud exerci tation ullamcorper suscipit lobortis nisl ut aliquip ex ea commodo consequat. Duis autem vel eum iriure dolor in hendrerit in vulputate velit esse molestie consequat, vel illum dolore eu feugiat nulla facilisis at vero eros et accumsan et iusto odio dignissim qui blandit praesent luptatum zzril delenit augue duis dolore te feugait nulla facilisi.