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Open Access Publications from the University of California

Scholarly Works (8 results)

  • Article
  • Peer Reviewed
Faculty Publications (2007)

Several 2007 AGU Awards were presented at the Joint Assembly in Acapulco, Mexico. Winners were introduced by President Tim Killeen in a formal ceremony held on 25 May 2007. An honors fiesta followed the ceremony.

It is with great pleasure that we recognize and honor the accomplishments of Diane E. Wickland, the 2007 winner of the Edward A. Flinn III Award from the American Geophysical Union, for her pivotal contributions to the development of the emerging field of biogeosciences.

    Cover page: Diane Wickland receives 2007 Edward A. Flinn III awardCreative Commons 'BY' version 4.0 license
    • Thesis
    • Peer Reviewed
    UC Berkeley Electronic Theses and Dissertations (2013)

    Despite over three decades of active research, Human Immunodeficiency Virus Type I (HIV-1) represents a pressing and ongoing challenge to our ability to understand complex pathogens that threaten human health at global scale. This stems in part from the highly dynamic and multi-scale lifecycle of the virus, which is reflected in the necessity for multi-drug cocktails to suppress viral replication. A fundamental aspect of the HIV lifecycle is the insertion or integration across a plethora of sites in the human genome. From these sites of integration, the viral promoter coordinates multiple inputs from the cellular signaling environment, the local genetic and epigenetic context, and a virally encoded feedback circuit. Through integration of these inputs via a poorly understood transfer function, the viral promoter regulates the temporal probability of the expression of viral genes and ultimately the kinetics of the viral lifecycle. The HIV promoter, the long terminal repeat (LTR), is composed of a core TATA promoter and a large cis acting enhancer. Furthermore, two well-positioned nucleosomes form the basic epigenetic regulatory structures that regulate LTR output. These features are highly similar to endogenous mammalian promoters. Therefore, studies of the LTR can reveal insights relevant to HIV biology as well as mammalian gene control.

    HIV represents a highly attractive model system to apply large-scale experimental and computational analysis to systematically study the role of promoter architecture and genomic context in transcriptional regulation. Previous work demonstrated that the LTR operates in a stochastic regime, which results in large cell-to-cell differences in gene expression within clonal populations. In HIV model systems and natural circuits, it has been shown that such heterogeneity or noise can have dramatic phenotypic consequences. However, how such noise is related to the features of promoters, the local genomic context, and their interaction with genetic circuits and cell biology, is poorly understood.

    Here using combined large-scale experimental and computational analysis we develop systems to isolate and study the effects of viral integration positions, promoter cis acting architecture, transcriptional feedback and post-transcriptional processes on viral gene expression noise. Specifically, by using systematic experimental analysis of single integration clones coupled with computational modeling and statistical inference, we are able to link LTR gene expression noise to dynamic nucleosome occupancy. Furthermore, we develop a method to generate highly diverse combinatoric promoters that will enable systematic study of the LTR structure-function relationship. Additionally, we develop quantitative strategies to cluster highly heterogeneous feedback distributions and reveal characteristic moment scaling relationships. Lastly, using simulations and analysis of mRNA localization using RNA fluorescent in situ hybridization, we demonstrate that slow mRNA export can function as a low-pass filter to buffer the cytoplasm from the effects of noisy transcription. Together, these efforts reveal molecular and cellular processes underlying noisy gene expression. Furthermore, we develop novel systems level approaches and tools for the study of complexity in eukaryotic gene control.

      Cover page: Systematic Dissection of the Determinants of HIV Expression Noise
      • Article
      • Peer Reviewed
      UC Berkeley Previously Published Works (2010)
      Mammalian gene expression patterns, and their variability across populations of cells, are regulated by factors specific to each gene in concert with its surrounding cellular and genomic environment. Lentiviruses such as HIV integrate their genomes into semi-random genomic locations in the cells they infect, and the resulting viral gene expression provides a natural system to dissect the contributions of genomic environment to transcriptional regulation. Previously, we showed that expression heterogeneity and its modulation by specific host factors at HIV integration sites are key determinants of infected-cell fate and a possible source of latent infections. Here, we assess the integration context dependence of expression heterogeneity from diverse single integrations of a HIV-promoter/GFP-reporter cassette in Jurkat T-cells. Systematically fitting a stochastic model of gene expression to our data reveals an underlying transcriptional dynamic, by which multiple transcripts are produced during short, infrequent bursts, that quantitatively accounts for the wide, highly skewed protein expression distributions observed in each of our clonal cell populations. Interestingly, we find that the size of transcriptional bursts is the primary systematic covariate over integration sites, varying from a few to tens of transcripts across integration sites, and correlating well with mean expression. In contrast, burst frequencies are scattered about a typical value of several per cell-division time and demonstrate little correlation with the clonal means. This pattern of modulation generates consistently noisy distributions over the sampled integration positions, with large expression variability relative to the mean maintained even for the most productive integrations, and could contribute to specifying heterogeneous, integration-site-dependent viral production patterns in HIV-infected cells. Genomic environment thus emerges as a significant control parameter for gene expression variation that may contribute to structuring mammalian genomes, as well as be exploited for survival by integrating viruses.
        Cover page: HIV promoter integration site primarily modulates transcriptional burst size rather than frequency.
        • Article
        • Peer Reviewed
        Faculty Publications (2008)
        Ecosystems influence climate through multiple pathways, primarily by changing the energy, water, and greenhouse-gas balance of the atmosphere. Consequently, efforts to mitigate climate change through modification of one pathway, as with carbon in the Kyoto Protocol, only partially address the issue of ecosystem–climate interactions. For example, the cooling of climate that results from carbon sequestration by plants may be partially offset by reduced land albedo, which increases solar energy absorption and warms the climate. The relative importance of these effects varies with spatial scale and latitude. We suggest that consideration of multiple interactions and feedbacks could lead to novel, potentially useful climate-mitigation strategies, including greenhouse-gas reductions primarily in industrialized nations, reduced desertification in arid zones, and reduced deforestation in the tropics. Each of these strategies has additional ecological and societal benefits. Assessing the effectiveness of these strategies requires a more quantitative understanding of the interactions among feedback processes, their consequences at local and global scales, and the teleconnections that link changes occurring in different regions.
          Cover page: Changing feedbacks in the climate-biosphere systemCreative Commons 'BY' version 4.0 license
          • Article
          • Peer Reviewed
          Faculty Publications (2012)
          Fires in agricultural ecosystems emit greenhouse gases and aerosols that influence climate on multiple spatial and temporal scales. Annex 1 countries of the United Nations Framework Convention on Climate Change (UNFCCC), many of which ratified the Kyoto Protocol, are required to report emissions of CH4 and N2O from these fires annually. In this study, we evaluated several aspects of this reporting system, including the optimality of the crops targeted by the UNFCCC globally and within Annex 1 countries, and the consistency of emissions inventories among different countries. We also evaluated the success of individual countries in capturing interannual variability and long-term trends in agricultural fire activity. In our approach, we combined global high-resolution maps of crop harvest area and production, derived from satellite maps and ground-based census data, with Terra and Aqua Moderate Resolution Imaging Spectroradiometer (MODIS) measurements of active fires. At a global scale, we found that adding ground nuts (e.g., peanuts), cocoa, cotton and oil palm, and removing potato, oats, rye, and pulse other from the list of 14 crops targeted by the UNFCCC increased the percentage of active fires covered by the reporting system by 9%. Optimization led to a different recommended list for Annex 1 countries, requiring the addition of sunflower, cotton, rapeseed, and alfalfa and the removal of beans, sugarcane, pulse others, and tuber-root others. Extending emissions reporting to all Annex 1 countries (from the current set of 19 countries) would increase the efficacy of the reporting system from 6% to 15%, and further including several non-Annex 1 countries (Argentina, Brazil, China, India, Indonesia, Thailand, Kazakhstan, Mexico, and Nigeria) would capture over 55% of active fires in croplands worldwide. Analyses of interannual trends from the United States and Australia showed the importance of both intensity of fire use and crop production in controlling year-to-year variations in agricultural fire emissions. Remote sensing provides an effective means for evaluating some aspects of the current UNFCCC emissions reporting system; and, if combined with census data, field experiments and expert opinion, has the potential to improve the robustness of the next generation inventory system.
            Cover page: Evaluating greenhouse gas emissions inventories for agricultural burning using satellite observations of active firesCreative Commons 'BY' version 4.0 license
            • Article
            • Peer Reviewed
            UC Irvine Previously Published Works (2013)
            Several studies have shown that global crop production needs to double by 2050 to meet the projected demands from rising population, diet shifts, and increasing biofuels consumption. Boosting crop yields to meet these rising demands, rather than clearing more land for agriculture has been highlighted as a preferred solution to meet this goal. However, we first need to understand how crop yields are changing globally, and whether we are on track to double production by 2050. Using ∼2.5 million agricultural statistics, collected for ∼13,500 political units across the world, we track four key global crops-maize, rice, wheat, and soybean-that currently produce nearly two-thirds of global agricultural calories. We find that yields in these top four crops are increasing at 1.6%, 1.0%, 0.9%, and 1.3% per year, non-compounding rates, respectively, which is less than the 2.4% per year rate required to double global production by 2050. At these rates global production in these crops would increase by ∼67%, ∼42%, ∼38%, and ∼55%, respectively, which is far below what is needed to meet projected demands in 2050. We present detailed maps to identify where rates must be increased to boost crop production and meet rising demands.
              Cover page: Yield Trends Are Insufficient to Double Global Crop Production by 2050
              • Article
              • Peer Reviewed
              UC Berkeley Previously Published Works (2015)
              While gene expression noise has been shown to drive dramatic phenotypic variations, the molecular basis for this variability in mammalian systems is not well understood. Gene expression has been shown to be regulated by promoter architecture and the associated chromatin environment. However, the exact contribution of these two factors in regulating expression noise has not been explored. Using a dual-reporter lentiviral model system, we deconvolved the influence of the promoter sequence to systematically study the contribution of the chromatin environment at different genomic locations in regulating expression noise. By integrating a large-scale analysis to quantify mRNA levels by smFISH and protein levels by flow cytometry in single cells, we found that mean expression and noise are uncorrelated across genomic locations. Furthermore, we showed that this independence could be explained by the orthogonal control of mean expression by the transcript burst size and noise by the burst frequency. Finally, we showed that genomic locations displaying higher expression noise are associated with more repressed chromatin, thereby indicating the contribution of the chromatin environment in regulating expression noise.
                Cover page: Orthogonal control of expression mean and variance by epigenetic features at different genomic loci.
                • Article
                • Peer Reviewed
                UC Irvine Previously Published Works (2011)
                Increasing population and consumption are placing unprecedented demands on agriculture and natural resources. Today, approximately a billion people are chronically malnourished while our agricultural systems are concurrently degrading land, water, biodiversity and climate on a global scale. To meet the world's future food security and sustainability needs, food production must grow substantially while, at the same time, agriculture's environmental footprint must shrink dramatically. Here we analyse solutions to this dilemma, showing that tremendous progress could be made by halting agricultural expansion, closing 'yield gaps' on underperforming lands, increasing cropping efficiency, shifting diets and reducing waste. Together, these strategies could double food production while greatly reducing the environmental impacts of agriculture.
                  Cover page: Solutions for a cultivated planetCreative Commons 'BY' version 4.0 license
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