In the evolutionary transition from unicellular to multicellular organisms, single cells assemble into highly organized tissues and cooperatively carry out physiological functions. To act as an integrated system, individual cells communicate with each other extensively through signaling at the cellular interface. Cell-surface signaling thus controls almost every aspect of the development and physiology of multicellular organisms. Taking the nervous system as an example, cell-surface wiring molecules dictate the precise assembly of the neural network during development, while neurotransmitter receptors and ion channels mediate synaptic transmission and plasticity in adults. Delineating the cell-surface signaling is therefore crucial for understanding the organizing principles and operating mechanisms of multicellular systems. My dissertation research integrates method development and mechanistic interrogation to investigate cell-surface signaling in neural circuit assembly. My collaborators and I developed, for the first time to my knowledge, a method for quantitatively profiling cell-surface proteomes in intact tissues with cell-type and spatiotemporal specificities. Applying this method to Drosophila olfactory projection neurons (PNs), I captured cell-surface proteomes of developing and mature PNs and observed globally coordinated dynamics of PN surface proteins corresponding to the wiring and functional stages of the olfactory circuit, providing the first systemic view on how neuronal surface evolves in development. A proteome-instructed in vivo screen identified 20 new cell-surface molecules regulating neural circuit assembly, many of which belong to evolutionarily conserved protein families not previously linked to neural development. These discoveries highlight the power of this new method in uncovering new regulators of brain wiring. Notably, this method should be readily applicable for profiling proteins on the surface of other cell types, tissues, and organisms, far beyond the fly olfactory circuit. In a complementary set of studies on the Plexin B receptor, I developed a generalizable protein tagging approach that reveals cell-type-specific endogenous protein distribution in vivo. Combining this tagging approach and genetic analyses, we found that the Plexin B receptor uses multiple molecular strategies: temporally-regulated protein distribution, level-dependent signaling, and divergent engagement of signaling motifs, to sequentially instruct several distinct steps of axon targeting. These include axon-axon interaction, axon guidance, and synaptic partner selection. Our findings illustrate how a single molecule achieves multi-functionality while preserving its signal specificity in brain wiring. In summary, this dissertation combines quantitative multi-omic profiling and in vivo mechanistic interrogation to elucidate the systemic properties and molecular bases of cell-surface signaling underlying the precise wiring of neural circuits.

The brain ... There is no other part of the human anatomy that is so intriguing. How does it develop and function and why does it sometimes, tragically, degenerate? The answers are complex. In Discovering the Brain, science writer Sandra Ackerman cuts through the complexity to bring this vital topic to the public. The 1990s were declared the "Decade of the Brain" by former President Bush, and the neuroscience community responded with a host of new investigations and conferences. Discovering the Brain is based on the Institute of Medicine conference, Decade of the Brain: Frontiers in Neuroscience and Brain Research. Discovering the Brain is a "field guide" to the brainâ€"an easy-to-read discussion of the brain's physical structure and where functions such as language and music appreciation lie. Ackerman examines: How electrical and chemical signals are conveyed in the brain. The mechanisms by which we see, hear, think, and pay attentionâ€"and how a "gut feeling" actually originates in the brain. Learning and memory retention, including parallels to computer memory and what they might tell us about our own mental capacity. Development of the brain throughout the life span, with a look at the aging brain. Ackerman provides an enlightening chapter on the connection between the brain's physical condition and various mental disorders and notes what progress can realistically be made toward the prevention and treatment of stroke and other ailments. Finally, she explores the potential for major advances during the "Decade of the Brain," with a look at medical imaging techniquesâ€"what various technologies can and cannot tell usâ€"and how the public and private sectors can contribute to continued advances in neuroscience. This highly readable volume will provide the public and policymakersâ€"and many scientists as wellâ€"with a helpful guide to understanding the many discoveries that are sure to be announced throughout the "Decade of the Brain."

Does science aim at providing an account of the world that is literally true or objectively true? Understanding the difference requires paying close attention to metaphor and its role in science. In The Third Lens, Andrew S. Reynolds argues that metaphors, like microscopes and other instruments, are a vital tool in the construction of scientific knowledge and explanations of how the world works. More than just rhetorical devices for conveying difficult ideas, metaphors provide the conceptual means with which scientists interpret and intervene in the world. Reynolds here investigates the role of metaphors in the creation of scientific concepts, theories, and explanations, using cell theory as his primary case study. He explores the history of key metaphors that have informed the field and the experimental, philosophical, and social circumstances under which they have emerged, risen in popularity, and in some cases faded from view. How we think of cells—as chambers, organisms, or even machines—makes a difference to scientific practice. Consequently, an accurate picture of how scientific knowledge is made requires us to understand how the metaphors scientists use—and the social values that often surreptitiously accompany them—influence our understanding of the world, and, ultimately, of ourselves. The influence of metaphor isn’t limited to how we think about cells or proteins: in some cases they can even lead to real material change in the very nature of the thing in question, as scientists use technology to alter the reality to fit the metaphor. Drawing out the implications of science’s reliance upon metaphor, The Third Lens will be of interest to anyone working in the areas of history and philosophy of science, science studies, cell and molecular biology, science education and communication, and metaphor in general.

The fruit fly Drosophila melanogaster offers the most powerful means of studying embryonic development in eukaryotes. New information from many different organ systems has accumulated rapidly in the past decade. This monograph, written by the most distinguished workers in the field, is the most authoritative and comprehensive synthesis of Drosophila developmental biology available and emphasizes the insights gained by molecular and genetic analysis. In two volumes, it is a lavishly illustrated, elegantly designed reference work illustrating principles of genetic regulation of embryogenesis that may apply to other eukaryotes.

Among the various nanomaterials, inorganic nanoparticles are extremely important in modern technologies. They can be easily and cheaply synthesized and mass produced, and for this reason, they can also be more readily integrated into applications. Inorganic Nanoparticles: Synthesis, Applications, and Perspectives presents an overview of these special materials and explores the myriad ways in which they are used. It addresses a wide range of topics, including: Application of nanoparticles in magnetic storage media Use of metal and oxide nanoparticles to improve performance of oxide thin films as conducting media in commercial gas and vapor sensors Advances in semiconductors for light-emitting devices and other areas related to the energy sector, such as solar energy and energy storage devices (fuel cells, rechargeable batteries, etc.) The expanding role of nanosized particles in the field of catalysis, art conservation, and biomedicine The book’s contributors address the growing global interest in the application of inorganic nanoparticles in various technological sectors. Discussing advances in materials, device fabrication, and large-scale production—all of which are urgently required to reduce global energy demands—they cover innovations in areas such as solid-state lighting, detailing how it still offers higher efficiency but higher costs, compared to conventional lighting. They also address the impact of nanotechnology in the biomedical field, focusing on topics such as quantum dots for bioimaging, nanoparticle-based cancer therapy, drug delivery, antibacterial agents, and more. Fills the informational gap on the wide range of applications for inorganic nanoparticles in areas including biomedicine, electronics, storage media, conservation of cultural heritage, optics, textiles, and cosmetics Assembling work from an array of experts at the top of their respective fields, this book delivers a useful analysis of the vast scope of existing and potential applications for inorganic nanoparticles. Versatile as either a professional research resource or textbook, this effective tool elucidates fundamentals and current advances associated with design, characterization, and application development of this promising and ever-evolving device.