Carnegie Institution for Science

Stanford, CA, United States

Carnegie Institution for Science

Stanford, CA, United States
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Agency: GTR | Branch: STFC | Program: | Phase: Research Grant | Award Amount: 879.19K | Year: 2016

How from a cloud of dust and gas did we arrive at a planet capable of supporting life? This is one of the most fundamental of questions, and engages everyone from school children to scientists. We now know much of the answer: We know that stars, such as our Sun, form by the collapse of interstellar clouds of dust and gas. We know that planets, such as Earth, are constructed in a disk around their host star known as the planetary nebula, formed by the rotation of the collapsing cloud of dust and gas. We know that 4.5 billion years ago in the solar nebula, surrounding the young Sun, all the objects in our Solar System were created through a process called accretion. And among all those bodies the only habitable world yet discovered on which life evolved is Earth. There is, however, much that we still do not know about how our Solar System formed. Why, for example, are all the planets so different? Why is Venus an inferno with a thick carbon dioxide atmosphere, Mars a frozen rock with a thin atmosphere, and Earth a haven for life? The answer lies in events that predated the assembly of these planets; it lies in the early history of the nebula and the events that occurred as fine-dust stuck together to form larger objects known as planetesimals; and in how those planetesimals changed through collisions, heating and the effects of water to become the building blocks of planets. Our research will follow the evolution of planetary materials from the origins of the first dust grains in the protoplanetary disk, through the assembly of planetesimals within the solar nebula to the modification of these objects as and after they became planets. Evidence preserved in meteorites provides a record of our Solar Systems evolution. Meteorites, together with cosmic dust particles, retain the fine-dust particles from the solar nebula. These dust grains are smaller than a millionth of a metre but modern microanalysis can expose their minerals and compositions. We will study the fine-grained components of meteorites and cosmic dust to investigate how fine-dust began accumulating in the solar nebula; how heating by an early hot nebula and repeated short heating events from collisions affected aggregates of dust grains; and whether magnetic fields helped control the distribution of dust in the solar nebula. We will also use numerical models to simulate how the first, fluffy aggregates of dust were compacted to become rock. As well as the rocky and metallic materials that make up the planets, our research will examine the source of Earths water and the fate of organic materials that were crucial to the origins of life. By analysing the isotopes of the volatile elements Zn, Cd and Te in meteorites and samples of Earth, Moon and Mars we will establish the source and timing of water and other volatiles delivered to the planets in the inner Solar System. In addition, through newly developed methods we can trace the history of organic matter in meteorites from their formation in interstellar space, through the solar nebula and into planetesimals. Reading the highly sensitive record in organic matter will reveal how cosmic chemistry furnished the Solar System with the raw materials for life. Once the planets finally formed, their materials continued to change by surface processes such as impacts and the flow of water. Our research will examine how impacts of asteroids and comets shaped planetary crusts and whether this bombardment endangered or aided the emergence of life. We will also study the planet Mars, which provides a second example of a planetary body on which life could have appeared. Imagery of ancient lakes on Mars will reveal a crucial period in the planets history, when global climate change transformed the planet into an arid wasteland, to evaluate the opportunity for organisms to adapt and survive and identify targets for future rover and sample return missions.

deCarvalho T.N.,Carnegie Institution for Science
Frontiers in neural circuits | Year: 2013

The dorsal habenular nuclei of the zebrafish epithalamus have become a valuable model for studying the development of left-right (L-R) asymmetry and its function in the vertebrate brain. The bilaterally paired dorsal habenulae exhibit striking differences in size, neuroanatomical organization, and molecular properties. They also display differences in their efferent connections with the interpeduncular nucleus (IPN) and in their afferent input, with a subset of mitral cells distributed on both sides of the olfactory bulb innervating only the right habenula. Previous studies have implicated the dorsal habenulae in modulating fear/anxiety responses in juvenile and adult zebrafish. It has been suggested that the asymmetric olfactory-habenula pathway (OB-Ha), revealed by selective labeling from an lhx2a:YFP transgene, mediates fear behaviors elicited by alarm pheromone. Here we show that expression of the fam84b gene demarcates a unique region of the right habenula that is the site of innervation by lhx2a:YFP-labeled olfactory axons. Upon ablation of the parapineal, which normally promotes left habenular identity; the fam84b domain is present in both dorsal habenulae and lhx2a:YFP-labeled olfactory bulb neurons form synapses on the left and the right side. To explore the relevance of the asymmetric olfactory projection and how it might influence habenular function, we tested activation of this pathway using odorants known to evoke behaviors. We find that alarm substance or other aversive odors, and attractive cues, activate fos expression in subsets of cells in the olfactory bulb but not in the lhx2a:YFP expressing population. Moreover, neither alarm pheromone nor chondroitin sulfate elicited fos activation in the dorsal habenulae. The results indicate that L-R asymmetry of the epithalamus sets the directionality of olfactory innervation, however, the lhx2a:YFP OB-Ha pathway does not appear to mediate fear responses to aversive odorants.

Kormendy J.,University of Texas at Austin | Ho L.C.,Carnegie Institution for Science
Annual Review of Astronomy and Astrophysics | Year: 2013

Supermassive black holes (BHs) have been found in 85 galaxies by dynamical modeling of spatially resolved kinematics. The Hubble Space Telescope revolutionized BH research by advancing the subject from its proof-of-concept phase into quantitative studies of BH demographics. Most influential was the discovery of a tight correlation between BH mass and the velocity dispersion σ of the bulge component of the host galaxy. Together with similar correlations with bulge luminosity and mass, this led to the widespread belief that BHs and bulges coevolve by regulating each other's growth. Conclusions based on one set of correlations from in brightest cluster ellipticals to in the smallest galaxies dominated BH work for more than a decade. New results are now replacing this simple story with a richer and more plausible picture in which BHs correlate differently with different galaxy components. A reasonable aim is to use this progress to refine our understanding of BH-galaxy coevolution. BHs with masses of 105-106Mȯ are found in many bulgeless galaxies. Therefore, classical (elliptical-galaxy-like) bulges are not necessary for BH formation. On the other hand, although they live in galaxy disks, BHs do not correlate with galaxy disks. Also, any correlations with the properties of disk-grown pseudobulges and dark matter halos are weak enough to imply no close coevolution. The above and other correlations of host-galaxy parameters with each other and with suggest that there are four regimes of BH feedback. (1) Local, secular, episodic, and stochastic feeding of small BHs in largely bulgeless galaxies involves too little energy to result in coevolution. (2) Global feeding in major, wet galaxy mergers rapidly grows giant BHs in short-duration, quasar-like events whose energy feedback does affect galaxy evolution. The resulting hosts are classical bulges and coreless-rotating-disky ellipticals. (3) After these AGN phases and at the highest galaxy masses, maintenance-mode BH feedback into X-ray-emitting gas has the primarily negative effect of helping to keep baryons locked up in hot gas and thereby keeping galaxy formation from going to completion. This happens in giant, core-nonrotating-boxy ellipticals. Their properties, including their tight correlations between and core parameters, support the conclusion that core ellipticals form by dissipationless major mergers. They inherit coevolution effects from smaller progenitor galaxies. Also, (4) independent of any feedback physics, in BH growth modes 2 and 3, the averaging that results from successive mergers plays a major role in decreasing the scatter in correlations from the large values observed in bulgeless and pseudobulge galaxies to the small values observed in giant elliptical galaxies.Copyright ©2013 by Annual Reviews. All rights reserved.

Bermejo C.,Carnegie Institution for Science
Nature protocols | Year: 2011

Optical sensors allow dynamic quantification of metabolite levels with subcellular resolution. Here we describe protocols for analyzing cytosolic glucose levels in yeast using genetically encoded Förster resonance energy transfer (FRET) sensors. FRET glucose sensors with different glucose affinities (K(d)) covering the low nano- to mid- millimolar range can be targeted genetically to the cytosol or to subcellular compartments. The sensors detect the glucose-induced conformational change in the bacterial periplasmic glucose/galactose binding protein MglB using FRET between two fluorescent protein variants. Measurements can be performed with a single sensor or multiple sensors in parallel. In one approach, cytosolic glucose accumulation is measured in yeast cultures in a 96-well plate using a fluorimeter. Upon excitation of the cyan fluorescent protein (CFP), emission intensities of CFP and YFP (yellow fluorescent protein) are captured before and after glucose addition. FRET sensors provide temporally resolved quantitative data of glucose for the compartment of interest. In a second approach, reversible changes of cytosolic free glucose are measured in individual yeast cells trapped in a microfluidic platform, allowing perfusion of different solutions while FRET changes are monitored in a microscope setup. By using the microplate fluorimeter protocol, 96 cultures can be measured in less than 1 h; analysis of single cells of a single genotype can be completed in <2 h. FRET-based analysis has been performed with glucose, maltose, ATP and zinc sensors, and it can easily be adapted for high-throughput screening using a wide spectrum of sensors.

Berry J.A.,Carnegie Institution for Science
Annual Review of Plant Biology | Year: 2012

An overriding interest in photosynthesis has propelled my wanderings from chemist to biochemist to plant physiologist and on to global topics. Equations and models have been organizing principles along the way. This fascination started as a reaction to difficulties with written communication, but it has proven to be quite useful in moving across different levels of organization. I conclude with some discussion of the importance of Earth system models for understanding and predicting how human activities may influence the climate, environment, and biota in the future, and some ideas about how disciplinary science might make larger contributions to this interdisciplinary problem. (Note: Selected references are available from the Carnegie Institution Web site at © 2012 by Annual Reviews. All rights reserved.

Hou B.H.,Carnegie Institution for Science
Nature protocols | Year: 2011

Knowledge of the in vivo levels, distribution and flux of ions and metabolites is crucial to our understanding of physiology in both healthy and diseased states. The quantitative analysis of the dynamics of ions and metabolites with subcellular resolution in vivo poses a major challenge for the analysis of metabolic processes. Genetically encoded Förster resonance energy transfer (FRET) sensors can be used for real-time in vivo detection of metabolites. FRET sensor proteins, for example, for glucose, can be targeted genetically to any cellular compartment, or even to subdomains (e.g., a membrane surface), by adding signal sequences or fusing the sensors to specific proteins. The sensors can be used for analyses in individual mammalian cells in culture, in tissue slices and in intact organisms. Applications include gene discovery, high-throughput drug screens or systematic analysis of regulatory networks affecting uptake, efflux and metabolism. Quantitative analyses obtained with the help of FRET sensors for glucose or other ions and metabolites provide valuable data for modeling of flux. Here we provide a detailed protocol for monitoring glucose levels in the cytosol of mammalian cell cultures through the use of FRET glucose sensors; moreover, the protocol can be used for other ions and metabolites and for analyses in other organisms, as has been successfully demonstrated in bacteria, yeast and even intact plants. The whole procedure typically takes ∼4 d including seeding and transfection of mammalian cells; the FRET-based analysis of transfected cells takes ∼5 h.

Chen L.-Q.,Carnegie Institution for Science
New Phytologist | Year: 2014

Many intercellular solute transport processes require an apoplasmic step, that is, efflux from one cell and subsequent uptake by an adjacent cell. Cellular uptake transporters have been identified for many solutes, including sucrose; however, efflux transporters have remained elusive for a long time. Cellular efflux of sugars plays essential roles in many processes, such as sugar efflux as the first step in phloem loading, sugar efflux for nectar secretion, and sugar efflux for supplying symbionts such as mycorrhiza, and maternal efflux for filial tissue development. Furthermore, sugar efflux systems can be hijacked by pathogens for access to nutrition from hosts. Mutations that block recruitment of the efflux mechanism by the pathogen thus cause pathogen resistance. Until recently, little was known regarding the underlying mechanism of sugar efflux. The identification of sugar efflux carriers, SWEETs (Sugars Will Eventually be Exported Transporters), has shed light on cellular sugar efflux. SWEETs appear to function as uniporters, facilitating diffusion of sugars across cell membranes. Indeed, SWEETs probably mediate sucrose efflux from putative phloem parenchyma into the phloem apoplasm, a key step proceeding phloem loading. Engineering of SWEET mutants using transcriptional activator-like effector nuclease (TALEN)-based genomic editing allowed the engineering of pathogen resistance. The widespread expression of the SWEET family promises to provide insights into many other cellular efflux mechanisms. © 2013 New Phytologist Trust.

Nizami Z.,Carnegie Institution for Science
Cold Spring Harbor perspectives in biology | Year: 2010

The Cajal body (CB) is a nuclear organelle present in all eukaryotes that have been carefully studied. It is identified by the signature protein coilin and by CB-specific RNAs (scaRNAs). CBs contain high concentrations of splicing small nuclear ribonucleoproteins (snRNPs) and other RNA processing factors, suggesting that they are sites for assembly and/or posttranscriptional modification of the splicing machinery of the nucleus. The histone locus body (HLB) contains factors required for processing histone pre-mRNAs. As its name implies, the HLB is associated with the genes that code for histones, suggesting that it may function to concentrate processing factors at their site of action. CBs and HLBs are present throughout the interphase of the cell cycle, but disappear during mitosis. The biogenesis of CBs shows the features of a self-organizing structure.

Barton M.K.,Carnegie Institution for Science
Developmental Biology | Year: 2010

The shoot apical meristem of angiosperm plants generates leaf, stem and floral structures throughout the plant's lifetime. To do this, the plant must maintain a population of stem cells within the meristem while at the same time carefully controlling the placement and establishment of new leaf primordia. As there is little cell rearrangement in plants, underlying patterning mechanisms must exert careful control of cell division rates and orientations to achieve the correct final form. It has been twenty years since the first genes controlling meristem development were molecularly cloned. In the intervening decades, our understanding of the inner workings directing meristem development has increased enormously. This review summarizes our current knowledge of how the meristem functions as a persistent organ generating center. The story that emerges is one in which transcription factor activity combines with the action of the classic plant growth regulators auxin and cytokinin and with the action of more recently discovered small peptides to control proliferation and cell fate in the shoot apical meristem. © 2009 Elsevier Inc.

Kim T.-W.,Carnegie Institution for Science | Wang Z.-Y.,Carnegie Institution for Science
Annual Review of Plant Biology | Year: 2010

Brassinosteroids (BRs) are growth-promoting steroid hormones in plants. Genetic studies in Arabidopsis illustrated the essential roles of BRs in a wide range of developmental processes and helped identify many genes involved in BR biosynthesis and signal transduction. Recently, proteomic studies identified missing links. Together, these approaches established the BR signal transduction cascade, which includes BR perception by the BRI1 receptor kinase at the cell surface, activation of BRI1/BAK1 kinase complex by transphosphorylation, subsequent phosphorylation of the BSK kinases, activation of the BSU1 phosphatase, dephosphorylation and inactivation of the BIN2 kinase, and accumulation of unphosphorylated BZR transcription factors in the nucleus. Mass spectrometric analyses are providing detailed information on the phosphorylation events involved in each step of signal relay. Thus, the BR signaling pathway provides a paradigm for understanding receptor kinase-mediated signal transduction as well as tools for the genetic improvement of the productivity of crop plants. Copyright © 2010 by Annual Reviews. All rights reserved.

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