The Sciences
Emerging Areas of Research
Today’s most promising science involves a change in scale—storage of information in a small space, manipulation of tiny bits of matter, and the imaging of biological processes once hidden from our view. Researchers have shifted their focus from the microscopic to the submicroscopic in biology, chemistry, physics, and geology. Yale has established two new interdisciplinary programs, the Institute for Nanoscale Research and the Center for Genomics and Proteomics. Funding for these initiatives is a core priority of the Yale Tomorrow campaign.
A roadmap for nanoscience
The science of quantum mechanics, that fuzzy realm where minute particles can occupy two locations at one time, helped engineers of the twentieth century devise electronic marvels such as the laser, transistor, and microchip—devices that paved the way for virtually every modern convenience. Yet these familiar inventions still operate according to the laws of classical physics. Exploiting the exotic physics that holds sway at very small scales, Yale scientists are now poised to create machines that actually operate on the quantum level. At the center of this breakthrough is the quantum bit, or qubit.
Tiny and fleeting by most standards, the qubit is a long-lived giant in the quantum world, a mass of electrons coaxed into a quantum state. Residing on a fleck of sapphire in a supercooled bath of liquid helium, the qubit is a precisely controlled sliver of aluminum just one one-millionth of a meter wide. Its tip, a quantum machine analogous to the on-off bit in a classical computer, contains either 100,000,000 or 100,000,001 electrons—and for a fraction of a second at a time, it contains both numbers at once.
“We used to think of this superposition state, where nothing is certain, as a bug in quantum mechanics,” explains physicist Steven Girvin. “Then a few years ago, we realized that it could be a benefit. Imagine a computer circuit that can use superpositions to calculate all possible variables of a problem at the same time.” With applied physicists Robert Schoelkopf and Michel Devoret, Girvin is taking the first steps toward a practical qubit—and one day, a new generation of superfast computers.
Girvin and his colleagues are also blazing trails for the Yale Institute for Nanoscale Research, an initiative launched in 2006 to focus on nanoscale science and its applications. These scientists are not only acquiring the technical know-how to make devices only a few molecules high, but also forming the professional ties that make interdisciplinary work at Yale so successful.
An interdisciplinary approach
Mark Saltzman, a biomedical engineer, is already pursuing several lines of research that rely on nano-sized particles. With Jordan Pober, a colleague at the School of Medicine, Saltzman is creating vascular networks that can be implanted in the human body. The scientists grow genetically engineered endothelial cells on a polymer scaffold, forming structures that will one day replace vascular networks damaged by diseases like diabetes or arterial sclerosis. To speed up the formation of the networks, Saltzman has synthesized microparticles only 10 to 20 microns wide that deliver growth factors to the developing tissues.
Another interdisciplinary project allies Saltzman with biomedical engineer Tarek Fahmy and Medical School researchers Ira Mellman and Michael Caplan. This team uses microparticles to encapsulate vaccines, which can then be delivered orally—a crucial step for developing countries, which lack the infrastructure to distribute injected vaccines to their populations. To make their particles more efficient at prompting an immune response, Saltzman and Fahmy reduced their size from 1 micron to just 100 nanometers in width. Now the team is adding “modules” that help the particle enter a cell, bind to receptors there, and release its vaccine into the surrounding tissue. Human trials are just a few years off.
The work of Girvin and Saltzman represents just a few of the disciplines that will benefit from the resources of the Institute for Nanoscale Research in the coming decade. As this institute grows, it will provide faculty support, research funds, and specialized equipment for experiments in nanoelectronics, quantum information, photonics, and biomaterials. These lines of inquiry will vastly expand our fundamental knowledge of the universe and lead to applications we can scarcely imagine today.
The Yale Center for Genomics and Proteomics was founded in 2003 to explore the role of genes and proteins in mediating complex biological processes. Under the direction of biologist Michael Snyder, this interdisciplinary “center without walls” provides cutting-edge technologies and research opportunities to departments across the University. The center strengthens Yale’s capabilities in this critical area and attracts talented faculty and students to our campus.
Using genomics to build a better mosquito trap
Some scientific questions that seem small at first glance actually have enormous consequences. For biologist John Carlson, curiosity about an insect’s sense of smell has led to a breakthrough that could soon benefit millions of people.
Carlson’s lab uses genetics and bioinformatics to understand at the cellular level how the fruit fly detects and differentiates a wide range of odors. Collaborating with colleagues in the Department of Ecology and Evolutionary Biology, Carlson devised a computer program to look for specific odor receptors on the fly’s antennae. “We identified sixty odor receptors that bind with different compounds in the air,” says Carlson. “Then, by manipulating the genes that code for the receptors, we developed a system to quickly test what odors are preferred by each receptor.”
The question of insect olfaction is not trivial. Around the world, insects use their sense of smell to zero in on food sources, like crops, causing major losses to agriculture. And about half of the world’s population is affected by insect-borne diseases like dengue fever, malaria, and encephalitis. Carlson wondered if he could use his system to home in on specific odors that attract mosquitoes to human beings—and perhaps reduce the 500 million cases of malaria contracted each year.
Adapting his technique proved simple. Carlson and his colleagues have identified seventy-nine odor receptor genes in the mosquito, including a receptor in the female that responds to an odor in human sweat. With a Gates Foundation grant and in collaboration with Vanderbilt University, he is working with labs in Denmark, the Netherlands, and Africa to identify other compounds that attract or repel the insects. As highly attractive or repellent compounds are identified in the lab, field tests can determine whether they are practical as mosquito traps or repellent sprays—applications that may save many lives.
Uncovering the genetic basis of evolution
For Antonia Monteiro, genomics offers a window on evolution. “There are gaps in the fossil record,” she says, “that make it difficult to plot evolutionary change as a gradual process. How do you explain the sudden appearance of novel features, like feathers or hands, if transitional forms are missing?”
The answer may lie in the genome. Monteiro studies genes that code for eye-spots, the concentric circles that have evolved on butterfly wings. She suspects that a network of developmental genes responsible for leg development has been redirected to produce patterns of pigment on the wing. This accidental mutation conferred a survival advantage on the butterfly, so it was passed on through subsequent generations.
“If networks of genes work and change together,” Monteiro explains, “a simple mutation might co-opt the network and enable it to act in a new way. So even if a form lacks a precedent iSeptember 29, 2006 genome.”
To test this theory, Monteiro is using transgenic tools to see if she can turn the eyespot gene network on and off. “Can we develop extra spots, or lose the spots altogether?” she wonders. “I’m hoping to show that complex traits, put together via the action of many genes, can actually arise by way of simple mutations.”
So far, functional genetic tests have been limited to five nih model organisms. Expanding these techniques to a new species, Monteiro is pushing the limits of genomic science, even as she provides new ways to understand the origin of complex organisms.
In emerging areas like genomics or nanotechnology, strategically placed funding will not only strengthen our research initiatives, but also bring the benefits of progress to society as a whole. Reflecting the breadth of today’s science, Yale Tomorrow also supports major initiatives in human genetics, computational biology, biomedical engineering, sustainable energy production, and climate change. In each of these areas, our faculty researchers stand among the world’s leaders, and their discoveries will have a major impact on the future.
When clinical and bench scientists work together to understand human diseases, the potential benefits are enormous; new initiatives in research and healthcare delivery are securing a place for Yale as one of the world’s leading medical centers
