Department of Biology
The mission of the Department of Biology is to combine internationally recognized research programs with a commitment to the very best in undergraduate and graduate education. Work in the Department is impressively interdisciplinary. For example, faculty research programs include the characterization of global ecosystem biology; the use of model systems to dissect gene expression, mammalian development, behavior, disease and evolution; and the development of genomics tools to study the architecture of gene expression and genome evolution. This research breadth allows the Department of Biology to tackle important questions in biology in an environment that encourages discussion and collaboration across different disciplines. From such strength the department has built outstanding research and educational programs in Ecology, Evolution & Biodiversity; the Molecular Basis of Behavior; Plant Science; Microbial Biology; Cell & Developmental Biology; Molecular Biology & Genetics and Genomics & Bioinformatics that are available for undergraduate, graduate and post-doctoral scientists.
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Publication Regulatory Impact of RNA Secondary Structure across the Arabidopsis Transcriptome(2012-11-01) Li, Fan; Vandivier, Lee E; Willmann, Matthew R; Chen, Ying; Gregory, Brian DThe secondary structure of an RNA molecule plays an integral role in its maturation, regulation, and function. However, the global influence of this feature on plant gene expression is still largely unclear. Here, we use a high-throughput, sequencing-based, structure-mapping approach in conjunction with transcriptome-wide sequencing of rRNA-depleted (RNA sequencing), small RNA, and ribosome-bound RNA populations to investigate the impact of RNA secondary structure on gene expression regulation in Arabidopsis thaliana. From this analysis, we find that highly unpaired and paired RNAs are strongly correlated with euchromatic and heterochromatic epigenetic histone modifications, respectively, providing evidence that secondary structure is necessary for these RNA-mediated posttranscriptional regulatory pathways. Additionally, we uncover key structural patterns across protein-coding transcripts that indicate RNA folding demarcates regions of protein translation and likely affects microRNA-mediated regulation of mRNAs in this model plant. We further reveal that RNA folding is significantly anticorrelated with overall transcript abundance, which is often due to the increased propensity of highly structured mRNAs to be degraded and/or processed into small RNAs. Finally, we find that secondary structure affects mRNA translation, suggesting that this feature regulates plant gene expression at multiple levels. These findings provide a global assessment of RNA folding and its significant regulatory effects in a plant transcriptome.Publication Biological Oxygen Demand Optode Analysis of Coral Reef-Associated Microbial Communities Exposed to Algal Exudates(2013-07-16) Gregg, Allison K; Hatay, Mark; Haas, Andreas F; Robinett, Nathan L; Barott, Katie; Vermeij, Mark J.A; Marhaver, Kristen L; Meirelles, Pedro M; Thompson, Fabiano; Rohwer, ForestAlgae-derived dissolved organic matter has been hypothesized to induce mortality of reef building corals. One proposed killing mechanism is a zone of hypoxia created by rapidly growing microbes. To investigate this hypothesis, biological oxygen demand (BOD) optodes were used to quantify the change in oxygen concentrations of microbial communities following exposure to exudates generated by turf algae and crustose coralline algae (CCA). BOD optodes were embedded with microbial communities cultured from Montastraea annularis and Mussismilia hispida, and respiration was measured during exposure to turf and CCA exudates. The oxygen concentrations along the optodes were visualized with a low-cost Submersible Oxygen Optode Recorder (SOOpR) system. With this system we observed that exposure to exudates derived from turf algae stimulated higher oxygen drawdown by the coral-associated bacteria than CCA exudates or seawater controls. Furthermore, in both turf and CCA exudate treatments, all microbial communities (coral-, algae-associated and pelagic) contributed significantly to the observed oxygen drawdown. This suggests that the driving factor for elevated oxygen consumption rates is the source of exudates rather than the initially introduced microbial community. Our results demonstrate that exudates from turf algae may contribute to hypoxia-induced coral stress in two different coral genera as a result of increased biological oxygen demand of the local microbial community. Additionally, the SOOpR system developed here can be applied to measure the BOD of any culturable microbe or microbial community.Publication The Perfect Family: Decision Making in Biparental Care(2009-10-13) Akçay, Erol; Roughgarden, JoanBackground Previous theoretical work on parental decisions in biparental care has emphasized the role of the conflict between evolutionary interests of parents in these decisions. A prominent prediction from this work is that parents should compensate for decreases in each other's effort, but only partially so. However, experimental tests that manipulate parents and measure their responses fail to confirm this prediction. At the same time, the process of parental decision making has remained unexplored theoretically. We develop a model to address the discrepancy between experiments and the theoretical prediction, and explore how assuming different decision making processes changes the prediction from the theory. Model Description We assume that parents make decisions in behavioral time. They have a fixed time budget, and allocate it between two parental tasks: provisioning the offspring and defending the nest. The proximate determinant of the allocation decisions are parents' behavioral objectives. We assume both parents aim to maximize the offspring production from the nest. Experimental manipulations change the shape of the nest production function. We consider two different scenarios for how parents make decisions: one where parents communicate with each other and act together (the perfect family), and one where they do not communicate, and act independently (the almost perfect family). Conclusions/Significance The perfect family model is able to generate all the types of responses seen in experimental studies. The kind of response predicted depends on the nest production function, i.e. how parents' allocations affect offspring production, and the type of experimental manipulation. In particular, we find that complementarity of parents' allocations promotes matching responses. In contrast, the relative responses do not depend on the type of manipulation in the almost perfect family model. These results highlight the importance of the interaction between nest production function and how parents make decisions, factors that have largely been overlooked in previous models.Publication The Macronuclear Genome of Stentor coeruleus Reveals Tiny Introns in a Giant Cell(2017-02-20) Slabodnick, Mark M; Ruby, J. G; Reiff, Sarah B; Swart, Estienne C; Gosai, Sager J; Prabakaran, Sudhakaran; Witkowska, Ewa; Larue, Graham E; Gregory, Brian D; Nowacki, Mariusz; Derisi, Joseph; Roy, Scott W; Marshall, Wallace F; Sood, PranidhiThe giant, single-celled organism Stentor coeruleus has a long history as a model system for studying pattern formation and regeneration in single cells. Stentor [1, 2] is a heterotrichous ciliate distantly related to familiar ciliate models, such as Tetrahymena or Paramecium. The primary distinguishing feature of Stentor is its incredible size: a single cell is 1 mm long. Early developmental biologists, including T.H. Morgan [3], were attracted to the system because of its regenerative abilities—if large portions of a cell are surgically removed, the remnant reorganizes into a normal-looking but smaller cell with correct proportionality [2, 3]. These biologists were also drawn to Stentor because it exhibits a rich repertoire of behaviors, including light avoidance, mechanosensitive contraction, food selection, and even the ability to habituate to touch, a simple form of learning usually seen in higher organisms [4]. While early microsurgical approaches demonstrated a startling array of regenerative and morphogenetic processes in this single-celled organism, Stentor was never developed as a molecular model system. We report the sequencing of the Stentor coeruleus macronuclear genome and reveal key features of the genome. First, we find that Stentor uses the standard genetic code, suggesting that ciliate-specific genetic codes arose after Stentor branched from other ciliates. We also discover that ploidy correlates with Stentor’s cell size. Finally, in the Stentor genome, we discover the smallest spliceosomal introns reported for any species. The sequenced genome opens the door to molecular analysis of single-cell regeneration in Stentor.Publication CoRAL: Predicting Non-Coding RNAs from Small RNA-Sequencing Data(2013-08-01) Leung, Yuk Y; Ryvkin, Paul; Ungar, Lyle H; Gregory, Brian D; Wang, Li-SanThe surprising observation that virtually the entire human genome is transcribed means we know little about the function of many emerging classes of RNAs, except their astounding diversities. Traditional RNA function prediction methods rely on sequence or alignment information, which are limited in their abilities to classify the various collections of non-coding RNAs (ncRNAs). To address this, we developed Classification of RNAs by Analysis of Length (CoRAL), a machine learning-based approach for classification of RNA molecules. CoRAL uses biologically interpretable features including fragment length and cleavage specificity to distinguish between different ncRNA populations. We evaluated CoRAL using genome-wide small RNA sequencing data sets from four human tissue types and were able to classify six different types of RNAs with ∼80% cross-validation accuracy. Analysis by CoRAL revealed that microRNAs, small nucleolar and transposon-derived RNAs are highly discernible and consistent across all human tissue types assessed, whereas long intergenic ncRNAs, small cytoplasmic RNAs and small nuclear RNAs show less consistent patterns. The ability to reliably annotate loci across tissue types demonstrates the potential of CoRAL to characterize ncRNAs using small RNA sequencing data in less well-characterized organisms.Publication Immunolocalization of Proteins in Corals: The V-Type H+-ATPase Proton Pump(2015-09-05) Barott, Katie; Tresguerres, MartinHere we describe the immunolocalization of a membrane-bound proton pump, the V-type H+-ATPase (VHA), in tissues and isolated cells of scleractinian corals. Immunolocalization of coral proteins requires additional steps not required for various model organisms, such as decalcification of the coral skeleton for immunohistochemistry or removal of cells away from the skeleton for immunocytochemistry. The tissue and cell preparation techniques described here can be adapted for localization of other coral proteins, provided the appropriate validation steps have been taken for the primary antibodies and species of coral used. These techniques are important for improving our understanding of coral cell physiology.Publication Established and Potential Physiological Roles of Bicarbonate-Sensing Soluble Adenylyl Cyclase (sAC) in Aquatic Animals(2014-01-01) Tresguerres, Martin; Barott, Katie; Barron, Megan E; Roa, Jinae NSoluble adenylyl cyclase (sAC) is a recently recognized source of the signaling molecule cyclic AMP (cAMP) that is genetically and biochemically distinct from the classic G-protein-regulated transmembrane adenylyl cyclases (tmACs). Mammalian sAC is distributed throughout the cytoplasm and it may be present in the nucleus and inside mitochondria. sAC activity is directly stimulated by HCO3-, and sAC has been confirmed to be a HCO3- sensor in a variety of mammalian cell types. In addition, sAC can functionally associate with carbonic anhydrases to act as a de facto sensor of pH and CO2. The two catalytic domains of sAC are related to HCO3--regilated adenylyl cyclases from cyanobacteria, suggesting the cAMP pathway is an evolutionarily conserved mechanism for sensing CO2 levels and/or acid/base conditions. Reports of sAC in aquatic animals are still limited but are rapidly accumulating. In shark gills, sAC senses blood alkalosis and triggers compensatory H+ absorption. And in sea urchin sperm, sAC may participate in the initiation of flagellar movement and in the acrosome reaction. Bioinformatics and RT-PCR results reveal that sAC orthologs are present in most animal phyla. This review summarizes the current knowledge on the physiological roles of sAC in aquatic animals and suggests additional functions in which sAC may be involved.Publication Lamin B1 Depletion in Senescent Cells Triggers Large-Scale Changes in Gene Expression and the Chromatin Landscape(2013-08-15) Shah, Parisha P; Donahue, Greg; Otte, Gabriel; Capell, Brian C; Nelson, David M; Cao, Kajia; Aggarwala, Varun; Cruickshanks, Hazel A; Rai, Taranjit Singh; McBryan, Tony; Gregory, Brian D; Adams, Peter D; Berger, Shelley LSenescence is a stable proliferation arrest, associated with an altered secretory pathway, thought to promote tumor suppression and tissue aging. While chromatin regulation and lamin B1 down-regulation have been implicated as senescence effectors, functional interactions between them are poorly understood. We compared genome-wide Lys4 trimethylation on histone H3 (H3K4me3) and H3K27me3 distributions between proliferating and senescent human cells and found dramatic differences in senescence, including large-scale domains of H3K4me3- and H3K27me3-enriched “mesas” and H3K27me3-depleted “canyons.” Mesas form at lamin B1-associated domains (LADs) in replicative senescence and oncogene-induced senescence and overlap DNA hypomethylation regions in cancer, suggesting that pre-malignant senescent chromatin changes foreshadow epigenetic cancer changes. Hutchinson-Gilford progeria syndrome fibroblasts (mutant lamin A) also show evidence of H3K4me3 mesas, suggesting a link between premature chromatin changes and accelerated cell senescence. Canyons mostly form between LADs and are enriched in genes and enhancers. H3K27me3 loss is correlated with up-regulation of key senescence genes, indicating a link between global chromatin changes and local gene expression regulation. Lamin B1 reduction in proliferating cells triggers senescence and formation of mesas and canyons. Our data illustrate profound chromatin reorganization during senescence and suggest that lamin B1 down-regulation in senescence is a key trigger of global and local chromatin changes that impact gene expression, aging, and cancer.Publication ETHYLENE-INSENSITIVE5 Encodes a 5'→3' Exoribonuclease Required for Regulation of the EIN3-Targeting F-Box Proteins EDF1⁄2(2006-09-05) Olmedo, Gabriela; Guo, Hongwei; Gregory, Brian D; Nourizadeh, Saeid D; Aguilar-Henonin, Laura; Li, Hongjiang; An, Fengying; Guzman, Plinio; Ecker, Joseph REthylene is a gaseous plant growth regulator that controls a multitude of developmental and stress responses. Recently, the levels of Arabidopsis EIN3 protein, a key transcription factor mediating ethylene-regulated gene expression, have been demonstrated to increase in response to the presence of ethylene gas. Furthermore, in the absence of ethylene, EIN3 is quickly degraded through a ubiquitin/proteasome pathway mediated by two F-box proteins, EBF1 and EBF2. Here we report the identification of ETHYLENE-INSENSITIVE5 as the 5′→3′ exoribonuclease XRN4. Specifically, we demonstrate that EIN5 is a component of the ethylene signal transduction cascade acting downstream of CTR1 that is required for ethylene-mediated gene expression changes. Furthermore, we find that the ethylene insensitivity of ein5 mutant plants is a consequence of the over-accumulation of EBF1 and EBF2 mRNAs resulting in the under-accumulation of EIN3 even in the presence of ethylene gas. Together, our results suggest that the role of EIN5 in ethylene perception is to antagonize the negative feedback regulation on EIN3 by promoting EBF1 and EBF2 mRNA decay, which consequently allows the accumulation of EIN3 protein to trigger the ethylene response.Publication Metagenomic Analysis Indicates that Stressors Induce Production of Herpes-Like Viruses in Coral Porites compressa(2008-01-01) Thurber, Rebecca L.V; Barott, Katie; Hall, Dana; Liu, Hong; Rodriguez-Mueller, Beltran; Desnues, Christelle; Edwards, Robert A; Haynes, Matthew; Angly, Florent E; Wegley, Linda; Rohwer, ForestDuring the last several decades corals have been in decline and at least one-third of all coral species are now threatened by extinction. Coral disease has been a major contributor to this threat, but little is known about the responsible pathogens. To date most research has focused on bacterial and fungal diseases; however, viruses may also be important for coral health. Using a combination of empirical viral metagenomics and real-time PCR, we show that Porites compressa corals contain a suite of eukaryotic viruses, many related to the Herpesviridae. This coral-associated viral consortium was found to shift in response to abiotic stressors. In particular, when exposed to reduced pH, elevated nutrients, and thermal stress, the abundance of herpes-like viral sequences rapidly increased in 2 separate experiments. Herpes-like viral sequences were rarely detected in apparently healthy corals, but were abundant in a majority of stressed samples. In addition, surveys of the Nematostella and Hydra genomic projects demonstrate that even distantly related Cnidarians contain numerous herpes-like viral genes, likely as a result of latent or endogenous viral infection. These data support the hypotheses that corals experience viral infections, which are exacerbated by stress, and that herpes-like viruses are common in Cnidarians.