Scholars@Duke
Amy Susanne Gladfelter

Amy Susanne Gladfelter

Professor of Cell Biology
Cell Biology
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Selected Publications

A single septin from a polyextremotolerant yeast recapitulates many canonical functions of septin hetero-oligomers.

Journal Article Mol Biol Cell · October 1, 2024 Morphological complexity and plasticity are hallmarks of polyextremotolerant fungi. Septins are conserved cytoskeletal proteins and key contributors to cell polarity and morphogenesis. They sense membrane curvature, coordinate cell division, and influence ... Full text Link to item Cite

RNAs kiss and translate in germ granules.

Journal Article Nat Cell Biol · October 1, 2024 Full text Link to item Cite

Experimental Considerations for the Evaluation of Viral Biomolecular Condensates.

Journal Article Annual review of virology · September 2024 Biomolecular condensates are nonmembrane-bound assemblies of biological polymers such as protein and nucleic acids. An increasingly accepted paradigm across the viral tree of life is (a) that viruses form biomolecular condensates and (b) that ... Full text Cite

Intrinsically disordered sequences can tune fungal growth and the cell cycle for specific temperatures.

Journal Article Curr Biol · August 19, 2024 Temperature can impact every reaction essential to a cell. For organisms that cannot regulate their own temperature, adapting to temperatures that fluctuate unpredictably and on variable timescales is a major challenge. Extremes in the magnitude and freque ... Full text Link to item Cite

Drivers of Morphogenesis: Curvature Sensor Self-Assembly at the Membrane.

Journal Article Cold Spring Harb Perspect Biol · May 2, 2024 This review examines the relationships between membrane chemistry, curvature-sensing proteins, and cellular morphogenesis. Curvature-sensing proteins are often orders of magnitude smaller than the membrane curvatures they localize to. How are nanometer-sca ... Full text Link to item Cite

Mitigating transcription noise via protein sharing in syncytial cells.

Journal Article Biophys J · April 16, 2024 Bursty transcription allows nuclei to concentrate the work of transcribing mRNA into short, intermittent intervals, potentially reducing transcriptional interference. However, bursts of mRNA production can increase noise in protein abundances. Here, we for ... Full text Link to item Cite

Tools for live-cell imaging of cytoskeletal and nuclear behavior in the unconventional yeast, Aureobasidium pullulans.

Journal Article Mol Biol Cell · April 1, 2024 Aureobasidium pullulans is a ubiquitous fungus with a wide variety of morphologies and growth modes including "typical" single-budding yeast, and interestingly, larger multinucleate yeast than can make multiple buds in a single cell cycle. The study of A. ... Full text Link to item Cite

Syncytial Assembly Lines: Consequences of Multinucleate Cellular Compartments for Fungal Protein Synthesis.

Journal Article Results Probl Cell Differ · 2024 Fast growth and prodigious cellular outputs make fungi powerful tools in biotechnology. Recent modeling work has exposed efficiency gains associated with dividing the labor of transcription over multiple nuclei, and experimental innovations are opening new ... Full text Link to item Cite

Dynamical control enables the formation of demixed biomolecular condensates.

Journal Article Nat Commun · November 24, 2023 Cellular matter can be organized into compositionally distinct biomolecular condensates. For example, in Ashbya gossypii, the RNA-binding protein Whi3 forms distinct condensates with different RNA molecules. Using criteria derived from a physical framework ... Full text Link to item Cite

Malassezia is widespread and has undescribed diversity in the marine environment

Journal Article Fungal Ecology · October 1, 2023 There is substantial fungal diversity in marine environments where uncharacterized species may play important ecological roles. Malassezia, a genus of yeast generally associated with mammalian skins, is an example of a seemingly abundant marine fungus in o ... Full text Cite

Live-cell imaging of septins and cell polarity proteins in the growing dikaryotic vegetative hypha of the model mushroom Coprinopsis cinerea.

Journal Article Sci Rep · June 22, 2023 The developmental biology underlying the morphogenesis of mushrooms remains poorly understood despite the essential role of fungi in the terrestrial environment and global carbon cycle. The mushroom Coprinopsis cinerea is a leading model system for the mol ... Full text Link to item Cite

A gene duplication of a septin reveals a developmentally regulated filament length control mechanism.

Journal Article J Cell Biol · March 6, 2023 Septins are a family of conserved filament-forming proteins that function in multiple cellular processes. The number of septin genes within an organism varies, and higher eukaryotes express many septin isoforms due to alternative splicing. It is unclear if ... Full text Link to item Cite

RNA structure controls composition and network dynamics of condensates

Journal Article Biophysical journal · February 10, 2023 Full text Cite

The role of RNA condensation in reducing gene expression noise

Journal Article Biophysical journal · February 10, 2023 Full text Cite

Curvature sensing as an emergent property of multiscale assembly of septins.

Journal Article Proc Natl Acad Sci U S A · February 7, 2023 The ability of cells to sense and communicate their shape is central to many of their functions. Much is known about how cells generate complex shapes, yet how they sense and respond to geometric cues remains poorly understood. Septins are GTP-binding prot ... Full text Link to item Cite

Targeted secretion: Myosin V delivers vesicles through formin condensates.

Journal Article Curr Biol · November 7, 2022 Secretory vesicles are often delivered to very specific targets, like pre-synaptic terminals or cell tips, to focus exocytosis. New work suggests that a biomolecular condensate focuses actin filaments that deliver incoming vesicles through the condensate t ... Full text Link to item Cite

PRD-2 mediates clock-regulated perinuclear localization of clock gene RNAs within the circadian cycle of Neurospora.

Journal Article Proc Natl Acad Sci U S A · August 2, 2022 The transcription-translation negative feedback loops underlying animal and fungal circadian clocks are remarkably similar in their molecular regulatory architecture and, although much is understood about their central mechanism, little is known about the ... Full text Link to item Cite

Double-stranded RNA drives SARS-CoV-2 nucleocapsid protein to undergo phase separation at specific temperatures.

Journal Article Nucleic acids research · August 2022 Nucleocapsid protein (N-protein) is required for multiple steps in betacoronaviruses replication. SARS-CoV-2-N-protein condenses with specific viral RNAs at particular temperatures making it a powerful model for deciphering RNA sequence specificity in cond ... Full text Cite

Reconstitution of Septin Assembly at Membranes to Study Biophysical Properties and Functions.

Journal Article J Vis Exp · July 28, 2022 Most cells can sense and change their shape to carry out fundamental cell processes. In many eukaryotes, the septin cytoskeleton is an integral component in coordinating shape changes like cytokinesis, polarized growth, and migration. Septins are filament- ... Full text Link to item Cite

A single septin from a polyextremotolerant yeast recapitulates many canonical functions of septin hetero-oligomers.

Journal Article Mol Biol Cell · October 1, 2024 Morphological complexity and plasticity are hallmarks of polyextremotolerant fungi. Septins are conserved cytoskeletal proteins and key contributors to cell polarity and morphogenesis. They sense membrane curvature, coordinate cell division, and influence ... Full text Link to item Cite

RNAs kiss and translate in germ granules.

Journal Article Nat Cell Biol · October 1, 2024 Full text Link to item Cite

Experimental Considerations for the Evaluation of Viral Biomolecular Condensates.

Journal Article Annual review of virology · September 2024 Biomolecular condensates are nonmembrane-bound assemblies of biological polymers such as protein and nucleic acids. An increasingly accepted paradigm across the viral tree of life is (a) that viruses form biomolecular condensates and (b) that ... Full text Cite

Intrinsically disordered sequences can tune fungal growth and the cell cycle for specific temperatures.

Journal Article Curr Biol · August 19, 2024 Temperature can impact every reaction essential to a cell. For organisms that cannot regulate their own temperature, adapting to temperatures that fluctuate unpredictably and on variable timescales is a major challenge. Extremes in the magnitude and freque ... Full text Link to item Cite

Drivers of Morphogenesis: Curvature Sensor Self-Assembly at the Membrane.

Journal Article Cold Spring Harb Perspect Biol · May 2, 2024 This review examines the relationships between membrane chemistry, curvature-sensing proteins, and cellular morphogenesis. Curvature-sensing proteins are often orders of magnitude smaller than the membrane curvatures they localize to. How are nanometer-sca ... Full text Link to item Cite

Mitigating transcription noise via protein sharing in syncytial cells.

Journal Article Biophys J · April 16, 2024 Bursty transcription allows nuclei to concentrate the work of transcribing mRNA into short, intermittent intervals, potentially reducing transcriptional interference. However, bursts of mRNA production can increase noise in protein abundances. Here, we for ... Full text Link to item Cite

Tools for live-cell imaging of cytoskeletal and nuclear behavior in the unconventional yeast, Aureobasidium pullulans.

Journal Article Mol Biol Cell · April 1, 2024 Aureobasidium pullulans is a ubiquitous fungus with a wide variety of morphologies and growth modes including "typical" single-budding yeast, and interestingly, larger multinucleate yeast than can make multiple buds in a single cell cycle. The study of A. ... Full text Link to item Cite

Syncytial Assembly Lines: Consequences of Multinucleate Cellular Compartments for Fungal Protein Synthesis.

Journal Article Results Probl Cell Differ · 2024 Fast growth and prodigious cellular outputs make fungi powerful tools in biotechnology. Recent modeling work has exposed efficiency gains associated with dividing the labor of transcription over multiple nuclei, and experimental innovations are opening new ... Full text Link to item Cite

Dynamical control enables the formation of demixed biomolecular condensates.

Journal Article Nat Commun · November 24, 2023 Cellular matter can be organized into compositionally distinct biomolecular condensates. For example, in Ashbya gossypii, the RNA-binding protein Whi3 forms distinct condensates with different RNA molecules. Using criteria derived from a physical framework ... Full text Link to item Cite

Malassezia is widespread and has undescribed diversity in the marine environment

Journal Article Fungal Ecology · October 1, 2023 There is substantial fungal diversity in marine environments where uncharacterized species may play important ecological roles. Malassezia, a genus of yeast generally associated with mammalian skins, is an example of a seemingly abundant marine fungus in o ... Full text Cite

Live-cell imaging of septins and cell polarity proteins in the growing dikaryotic vegetative hypha of the model mushroom Coprinopsis cinerea.

Journal Article Sci Rep · June 22, 2023 The developmental biology underlying the morphogenesis of mushrooms remains poorly understood despite the essential role of fungi in the terrestrial environment and global carbon cycle. The mushroom Coprinopsis cinerea is a leading model system for the mol ... Full text Link to item Cite

A gene duplication of a septin reveals a developmentally regulated filament length control mechanism.

Journal Article J Cell Biol · March 6, 2023 Septins are a family of conserved filament-forming proteins that function in multiple cellular processes. The number of septin genes within an organism varies, and higher eukaryotes express many septin isoforms due to alternative splicing. It is unclear if ... Full text Link to item Cite

RNA structure controls composition and network dynamics of condensates

Journal Article Biophysical journal · February 10, 2023 Full text Cite

The role of RNA condensation in reducing gene expression noise

Journal Article Biophysical journal · February 10, 2023 Full text Cite

Curvature sensing as an emergent property of multiscale assembly of septins.

Journal Article Proc Natl Acad Sci U S A · February 7, 2023 The ability of cells to sense and communicate their shape is central to many of their functions. Much is known about how cells generate complex shapes, yet how they sense and respond to geometric cues remains poorly understood. Septins are GTP-binding prot ... Full text Link to item Cite

Targeted secretion: Myosin V delivers vesicles through formin condensates.

Journal Article Curr Biol · November 7, 2022 Secretory vesicles are often delivered to very specific targets, like pre-synaptic terminals or cell tips, to focus exocytosis. New work suggests that a biomolecular condensate focuses actin filaments that deliver incoming vesicles through the condensate t ... Full text Link to item Cite

PRD-2 mediates clock-regulated perinuclear localization of clock gene RNAs within the circadian cycle of Neurospora.

Journal Article Proc Natl Acad Sci U S A · August 2, 2022 The transcription-translation negative feedback loops underlying animal and fungal circadian clocks are remarkably similar in their molecular regulatory architecture and, although much is understood about their central mechanism, little is known about the ... Full text Link to item Cite

Double-stranded RNA drives SARS-CoV-2 nucleocapsid protein to undergo phase separation at specific temperatures.

Journal Article Nucleic acids research · August 2022 Nucleocapsid protein (N-protein) is required for multiple steps in betacoronaviruses replication. SARS-CoV-2-N-protein condenses with specific viral RNAs at particular temperatures making it a powerful model for deciphering RNA sequence specificity in cond ... Full text Cite

Reconstitution of Septin Assembly at Membranes to Study Biophysical Properties and Functions.

Journal Article J Vis Exp · July 28, 2022 Most cells can sense and change their shape to carry out fundamental cell processes. In many eukaryotes, the septin cytoskeleton is an integral component in coordinating shape changes like cytokinesis, polarized growth, and migration. Septins are filament- ... Full text Link to item Cite

Membrane surfaces regulate assembly of ribonucleoprotein condensates.

Journal Article Nat Cell Biol · April 2022 Biomolecular condensates organize biochemistry, yet little is known about how cells control the position and scale of these structures. In cells, condensates often appear as relatively small assemblies that do not coarsen into a single droplet despite thei ... Full text Link to item Cite

Dilute phase oligomerization can oppose phase separation and modulate material properties of a ribonucleoprotein condensate.

Journal Article Proc Natl Acad Sci U S A · March 29, 2022 SignificanceA large subclass of biomolecular condensates are linked to RNA regulation and are known as ribonucleoprotein (RNP) bodies. While extensive work has identified driving forces for biomolecular condensate formation, relatively little is known abou ... Full text Link to item Cite

Design considerations for analyzing protein translation regulation by condensates.

Journal Article RNA · January 2022 One proposed role for biomolecular condensates that contain RNA is translation regulation. In several specific contexts, translation has been shown to be modulated by the presence of a phase-separating protein and under conditions which promote phase separ ... Full text Link to item Cite

20 years of Developmental Cell: Looking forward.

Journal Article Dev Cell · December 6, 2021 In our 20th anniversary year, we reflect on how fields have changed since our first issue and here look to the future. In this collection of Voices, our writers speculate on the future: in terms of philosophy, cell states, cell processes, and then how to m ... Full text Link to item Cite

Quantitative single molecule RNA-FISH and RNase-free cell wall digestion in Neurospora crassa.

Journal Article Fungal Genet Biol · November 2021 Single molecule RNA-FISH (smFISH) is a valuable tool for analysis of mRNA spatial patterning in fixed cells that is underutilized in filamentous fungi. A primary complication for fixed-cell imaging in filamentous fungi is the need for enzymatic cell wall p ... Full text Link to item Cite

Evolution and Physiology of Amphibious Yeasts.

Book · October 8, 2021 Since the emergence of the first fungi some 700 million years ago, unicellular yeast-like forms have emerged multiple times in independent lineages via convergent evolution. While tens to hundreds of millions of years separate the independent evolution of ... Full text Link to item Cite

Interplay of septin amphipathic helices in sensing membrane-curvature and filament bundling.

Journal Article Mol Biol Cell · October 1, 2021 The curvature of the membrane defines cell shape. Septins are GTP-binding proteins that assemble into heteromeric complexes and polymerize into filaments at areas of micron-scale membrane curvature. An amphipathic helix (AH) domain within the septin comple ... Full text Link to item Cite

Getting droplets into shape.

Journal Article Science · September 10, 2021 Protein clusters at interfaces control sizes and properties of biomolecular condensates. ... Full text Link to item Cite

Role of spatial patterning of N-protein interactions in SARS-CoV-2 genome packaging.

Journal Article Biophys J · July 20, 2021 Viruses must efficiently and specifically package their genomes while excluding cellular nucleic acids and viral subgenomic fragments. Some viruses use specific packaging signals, which are conserved sequence or structure motifs present only in the full-le ... Full text Link to item Cite

Roadmap for the multiscale coupling of biochemical and mechanical signals during development.

Journal Article Phys Biol · April 14, 2021 The way in which interactions between mechanics and biochemistry lead to the emergence of complex cell and tissue organization is an old question that has recently attracted renewed interest from biologists, physicists, mathematicians and computer scientis ... Full text Link to item Cite

Culturing and Multiplexed Time-Lapse Imaging of Fungal Isolates from Marine and Coastal Environments.

Journal Article Curr Protoc · April 2021 Fungi play a crucial role in biogeochemical cycling and shaping biological communities at macro- and microcosmic scales. However, fungi have been largely overlooked in studies of marine ecology and microbiology. Here we present protocols for preparing cult ... Full text Link to item Cite

Moving beyond disease to function: Physiological roles for polyglutamine-rich sequences in cell decisions.

Journal Article Curr Opin Cell Biol · April 2021 Glutamine-rich tracts, also known as polyQ domains, have received a great deal of attention for their role in multiple neurodegenerative diseases, including Huntington's disease (HD), spinocerebellar ataxia (SCA), and others [22], [27]. Expansions in the n ... Full text Link to item Cite

RNA contributions to the form and function of biomolecular condensates.

Journal Article Nat Rev Mol Cell Biol · March 2021 Biomolecular condensation partitions cellular contents and has important roles in stress responses, maintaining homeostasis, development and disease. Many nuclear and cytoplasmic condensates are rich in RNA and RNA-binding proteins (RBPs), which undergo li ... Full text Link to item Cite

HSP70 chaperones RNA-free TDP-43 into anisotropic intranuclear liquid spherical shells.

Journal Article Science · February 5, 2021 The RNA binding protein TDP-43 forms intranuclear or cytoplasmic aggregates in age-related neurodegenerative diseases. In this study, we found that RNA binding-deficient TDP-43 (produced by neurodegeneration-causing mutations or posttranslational acetylati ... Full text Link to item Cite

The state of the septin cytoskeleton from assembly to function.

Journal Article Curr Opin Cell Biol · February 2021 Septins are conserved guanine nucleotide-binding proteins that polymerize into filaments at the cell cortex or in association with other cytoskeletal proteins, such as actin or microtubules. As integral players in many morphogenic and signaling events, sep ... Full text Link to item Cite

Genomic RNA Elements Drive Phase Separation of the SARS-CoV-2 Nucleocapsid.

Journal Article Mol Cell · December 17, 2020 We report that the SARS-CoV-2 nucleocapsid protein (N-protein) undergoes liquid-liquid phase separation (LLPS) with viral RNA. N-protein condenses with specific RNA genomic elements under physiological buffer conditions and condensation is enhanced at huma ... Full text Link to item Cite

Shed light in the dark lineages of the fungal tree of life—stres

Journal Article Life · December 1, 2020 The polyphyletic group of black fungi within the Ascomycota (Arthoniomycetes, Dothideomycetes, and Eurotiomycetes) is ubiquitous in natural and anthropogenic habitats. Partly because of their dark, melanin-based pigmentation, black fungi are resistant to s ... Full text Cite

Modeling the Mechanisms by Which Coexisting Biomolecular RNA-Protein Condensates Form.

Journal Article Bull Math Biol · November 24, 2020 Liquid-liquid phase separation is an emerging mechanism for intracellular organization. This work presents a mathematical model to examine molecular mechanisms that yield phase-separated droplets composed of different RNA-protein complexes. Using a Cahn-Hi ... Full text Link to item Cite

The hierarchical assembly of septins revealed by high-speed AFM.

Journal Article Nat Commun · October 8, 2020 Septins are GTP-binding proteins involved in diverse cellular processes including division and membrane remodeling. Septins form linear, palindromic heteromeric complexes that can assemble in filaments and higher-order structures. Structural studies reveal ... Full text Link to item Cite

Phosphoregulation provides specificity to biomolecular condensates in the cell cycle and cell polarity.

Journal Article J Cell Biol · July 6, 2020 Biomolecular condensation is a way of organizing cytosol in which proteins and nucleic acids coassemble into compartments. In the multinucleate filamentous fungus Ashbya gossypii, the RNA-binding protein Whi3 regulates the cell cycle and cell polarity thro ... Full text Link to item Cite

Spatial heterogeneity of the cytosol revealed by machine learning-based 3D particle tracking.

Journal Article Mol Biol Cell · July 1, 2020 The spatial structure and physical properties of the cytosol are not well understood. Measurements of the material state of the cytosol are challenging due to its spatial and temporal heterogeneity. Recent development of genetically encoded multimeric nano ... Full text Link to item Cite

FXR1 splicing is important for muscle development and biomolecular condensates in muscle cells.

Journal Article J Cell Biol · April 6, 2020 Fragile-X mental retardation autosomal homologue-1 (FXR1) is a muscle-enriched RNA-binding protein. FXR1 depletion is perinatally lethal in mice, Xenopus, and zebrafish; however, the mechanisms driving these phenotypes remain unclear. The FXR1 gene undergo ... Full text Link to item Cite

Guanidine hydrochloride reactivates an ancient septin hetero-oligomer assembly pathway in budding yeast.

Journal Article Elife · January 28, 2020 Septin proteins evolved from ancestral GTPases and co-assemble into hetero-oligomers and cytoskeletal filaments. In Saccharomyces cerevisiae, five septins comprise two species of hetero-octamers, Cdc11/Shs1-Cdc12-Cdc3-Cdc10-Cdc10-Cdc3-Cdc12-Cdc11/Shs1. Slo ... Full text Link to item Cite

Unconventional Cell Division Cycles from Marine-Derived Yeasts.

Journal Article Curr Biol · October 21, 2019 Fungi have been found in every marine habitat that has been explored; however, the diversity and functions of fungi in the ocean are poorly understood. In this study, fungi were cultured from the marine environment in the vicinity of Woods Hole, MA, USA, i ... Full text Link to item Cite

The Control Centers of Biomolecular Phase Separation: How Membrane Surfaces, PTMs, and Active Processes Regulate Condensation.

Journal Article Mol Cell · October 17, 2019 Biomolecular condensation is emerging as an essential process for cellular compartmentalization. The formation of biomolecular condensates can be driven by liquid-liquid phase separation, which arises from weak, multivalent interactions among proteins and ... Full text Link to item Cite

An amphipathic helix enables septins to sense micrometer-scale membrane curvature.

Journal Article J Cell Biol · April 1, 2019 Cell shape is well described by membrane curvature. Septins are filament-forming, GTP-binding proteins that assemble on positive, micrometer-scale curvatures. Here, we examine the molecular basis of curvature sensing by septins. We show that differences in ... Full text Link to item Cite

Zika Virus Protease Cleavage of Host Protein Septin-2 Mediates Mitotic Defects in Neural Progenitors.

Journal Article Neuron · March 20, 2019 Zika virus (ZIKV) targets neural progenitor cells in the brain, attenuates cell proliferation, and leads to cell death. Here, we describe a role for the ZIKV protease NS2B-NS3 heterodimer in mediating neurotoxicity through cleavage of a host protein requir ... Full text Link to item Cite

Marine fungi.

Journal Article Curr Biol · March 18, 2019 Fungi play a dominant role in terrestrial environments where they thrive in symbiotic associations with plants and animals and are integral to nutrient cycling in diverse ecosystems. Everywhere that moisture and a carbon source coexist in the terrestrial b ... Full text Link to item Cite

Fungi in the Marine Environment: Open Questions and Unsolved Problems.

Journal Article mBio · March 5, 2019 Terrestrial fungi play critical roles in nutrient cycling and food webs and can shape macroorganism communities as parasites and mutualists. Although estimates for the number of fungal species on the planet range from 1.5 to over 5 million, likely fewer th ... Full text Link to item Cite

Considerations and Challenges in Studying Liquid-Liquid Phase Separation and Biomolecular Condensates.

Journal Article Cell · January 24, 2019 Evidence is now mounting that liquid-liquid phase separation (LLPS) underlies the formation of membraneless compartments in cells. This realization has motivated major efforts to delineate the function of such biomolecular condensates in normal cells and t ... Full text Link to item Cite

Partial demixing of RNA-protein complexes leads to intradroplet patterning in phase-separated biological condensates.

Journal Article Phys Rev E · January 2019 An emerging mechanism for intracellular organization is liquid-liquid phase separation (LLPS). Found in both the nucleus and the cytoplasm, liquidlike droplets condense to create compartments that are thought to promote and inhibit specific biochemistry. I ... Full text Link to item Cite

A New Lens for RNA Localization: Liquid-Liquid Phase Separation.

Book · September 8, 2018 RNA localization mechanisms have been intensively studied and include localized protection of mRNA from degradation, diffusion-coupled local entrapment of mRNA, and directed transport of mRNAs along the cytoskeleton. While it is well understood how cells u ... Full text Link to item Cite

Principles of Systems Biology, No. 30.

Journal Article Cell Syst · July 25, 2018 This month: two examples of door-opening, innovative microscopy (Garcia and also Benzinger et al.), expanding our functional knowledge of bacteria by over 10,000 genes (Deutschbauer), and probing how RNA structure dictates inclusion in liquid-like droplets ... Full text Link to item Cite

mRNA structure determines specificity of a polyQ-driven phase separation.

Journal Article Science · May 25, 2018 RNA promotes liquid-liquid phase separation (LLPS) to build membraneless compartments in cells. How distinct molecular compositions are established and maintained in these liquid compartments is unknown. Here, we report that secondary structure allows mess ... Full text Link to item Cite

LITE microscopy: Tilted light-sheet excitation of model organisms offers high resolution and low photobleaching.

Journal Article J Cell Biol · May 7, 2018 Fluorescence microscopy is a powerful approach for studying subcellular dynamics at high spatiotemporal resolution; however, conventional fluorescence microscopy techniques are light-intensive and introduce unnecessary photodamage. Light-sheet fluorescence ... Full text Link to item Cite

Control of septin filament flexibility and bundling by subunit composition and nucleotide interactions.

Journal Article Mol Biol Cell · March 15, 2018 Septins self-assemble into heteromeric rods and filaments to act as scaffolds and modulate membrane properties. How cells tune the biophysical properties of septin filaments to control filament flexibility and length, and in turn the size, shape, and posit ... Full text Link to item Cite

Probing RNA Structure in Liquid-Liquid Phase Separation Using SHAPE-MaP.

Chapter · 2018 RNA is an integral component of many biological condensates. A variety of features of RNAs are linked to their function in biological phase separation. Length and negative charge provide fairly generic chemical inputs that drive condensation while sequence ... Full text Link to item Cite

The Unsolved Problem of How Cells Sense Micron-Scale Curvature.

Journal Article Trends Biochem Sci · December 2017 Membrane curvature is a fundamental feature of cells and their organelles. Much of what we know about how cells sense curved surfaces comes from studies examining nanometer-sized molecules on nanometer-scale curvatures. We are only just beginning to unders ... Full text Link to item Cite

Lessons from Yeast on How to Avoid Stress Eating.

Journal Article Dev Cell · October 9, 2017 Cellular survival during periods of acute environmental stress is essential for single-celled organisms. Reporting in Nature Cell Biology, Saad et al. (2017) identify reversible aggregation of the metabolic enzyme pyruvate kinase under environmental stress ... Full text Link to item Cite

What your PI forgot to tell you: why you actually might want a job running a research lab.

Journal Article Mol Biol Cell · July 1, 2017 A PhD in biomedical science and the critical thinking skills that it provides can open the door to many different careers. The current popular scientific press and blogosphere too often portray the job of a research-intensive faculty member and principal i ... Full text Link to item Cite

Non-model model organisms.

Journal Article BMC Biol · June 29, 2017 Model organisms are widely used in research as accessible and convenient systems to study a particular area or question in biology. Traditionally only a handful of organisms have been widely studied, but modern research tools are enabling researchers to ex ... Full text Link to item Cite

Analysis of septin reorganization at cytokinesis using polarized fluorescence microscopy

Journal Article Frontiers in Cell and Developmental Biology · May 3, 2017 Septins are conserved filament-forming proteins that act in diverse cellular processes. They closely associate with membranes and, in some systems, components of the cytoskeleton. It is not well understood how filaments assemble into higher-order structure ... Full text Cite

Dissection of molecular assembly dynamics by tracking orientation and position of single molecules in live cells.

Journal Article Proc Natl Acad Sci U S A · October 18, 2016 Regulation of order, such as orientation and conformation, drives the function of most molecular assemblies in living cells but remains difficult to measure accurately through space and time. We built an instantaneous fluorescence polarization microscope, ... Full text Link to item Cite

Clustered nuclei maintain autonomy and nucleocytoplasmic ratio control in a syncytium.

Journal Article Mol Biol Cell · July 1, 2016 Nuclei in syncytia found in fungi, muscles, and tumors can behave independently despite cytoplasmic translation and the homogenizing potential of diffusion. We use a dynactin mutant strain of the multinucleate fungus Ashbya gossypii with highly clustered n ... Full text Link to item Cite

Micron-scale plasma membrane curvature is recognized by the septin cytoskeleton.

Journal Article J Cell Biol · April 11, 2016 Cells change shape in response to diverse environmental and developmental conditions, creating topologies with micron-scale features. Although individual proteins can sense nanometer-scale membrane curvature, it is unclear if a cell could also use nanomete ... Full text Link to item Cite

Quantitative spatial analysis of transcripts in multinucleate cells using single-molecule FISH.

Journal Article Methods · April 1, 2016 mRNA positioning in the cell is important for diverse cellular functions and proper development of multicellular organisms. Single-molecule RNA FISH (smFISH) enables quantitative investigation of mRNA localization and abundance at the level of individual m ... Full text Link to item Cite

In vitro reconstitution of septin assemblies on supported lipid bilayers.

Journal Article Methods Cell Biol · 2016 Septins are polymerizing eukaryotic proteins that play conserved roles in cell cortex organization and are essential in many cell types. How septin dynamics and protein-protein interactions determine their function at the plasma membrane remains a mystery. ... Full text Link to item Cite

Nuclear autonomy in multinucleate fungi.

Journal Article Curr Opin Microbiol · December 2015 Within many fungal syncytia, nuclei behave independently despite sharing a common cytoplasm. Creation of independent nuclear zones of control in one cell is paradoxical considering random protein synthesis sites, predicted rapid diffusion rates, and well-m ... Full text Link to item Cite

How nontraditional model systems can save us.

Journal Article Mol Biol Cell · November 1, 2015 In this essay I would like to highlight how work in nontraditional model systems is an imperative for our society to prepare for problems we do not even know exist. I present examples of how discovery in nontraditional systems has been critical for fundame ... Full text Link to item Cite

RNA Controls PolyQ Protein Phase Transitions.

Journal Article Mol Cell · October 15, 2015 Compartmentalization in cells is central to the spatial and temporal control of biochemistry. In addition to membrane-bound organelles, membrane-less compartments form partitions in cells. Increasing evidence suggests that these compartments assemble throu ... Full text Link to item Cite

Life as a moving fluid: fate of cytoplasmic macromolecules in dynamic fungal syncytia.

Journal Article Curr Opin Microbiol · August 2015 In fungal syncytia dozens, or even millions of nuclei may coexist in a single connected cytoplasm. Recent discoveries have exposed some of the adaptations that enable fungi to marshall these nuclei to produce complex coordinated behaviors, including cell g ... Full text Link to item Cite

Septin Form and Function at the Cell Cortex.

Journal Article J Biol Chem · July 10, 2015 Septins are GTP-binding proteins that form filaments and higher-order structures on the cell cortex of eukaryotic cells and associate with actin and microtubule cytoskeletal networks. When assembled, septins coordinate cell division and contribute to cell ... Full text Link to item Cite

Absolute Arrangement of Subunits in Cytoskeletal Septin Filaments in Cells Measured by Fluorescence Microscopy.

Journal Article Nano Lett · June 10, 2015 We resolved the organization of subunits in cytoskeletal polymers in cells by light microscopy. Septin GTPases form linear complexes of about 32 nm length that polymerize into filaments. We visualized both termini of septin complexes by single molecule mic ... Full text Link to item Cite

Polarized Fluorescence Microscopy to Study Cytoskeleton Assembly and Organization in Live Cells.

Journal Article Curr Protoc Cell Biol · June 1, 2015 The measurement of not only the location but also the organization of molecules in live cells is crucial to understanding diverse biological processes. Polarized light microscopy provides a nondestructive means to evaluate order within subcellular domains. ... Full text Link to item Cite

Cytoskeletal dynamics: a view from the membrane.

Journal Article J Cell Biol · May 11, 2015 Many aspects of cytoskeletal assembly and dynamics can be recapitulated in vitro; yet, how the cytoskeleton integrates signals in vivo across cellular membranes is far less understood. Recent work has demonstrated that the membrane alone, or through membra ... Full text Link to item Cite

Biological Significance of Photoreceptor Photocycle Length: VIVID Photocycle Governs the Dynamic VIVID-White Collar Complex Pool Mediating Photo-adaptation and Response to Changes in Light Intensity.

Journal Article PLoS Genet · May 2015 Most organisms on earth sense light through the use of chromophore-bearing photoreceptive proteins with distinct and characteristic photocycle lengths, yet the biological significance of this adduct decay length is neither understood nor has been tested. I ... Full text Link to item Cite

MultiFocus Polarization Microscope (MF-PolScope) for 3D polarization imaging of up to 25 focal planes simultaneously.

Journal Article Opt Express · March 23, 2015 We have developed an imaging system for 3D time-lapse polarization microscopy of living biological samples. Polarization imaging reveals the position, alignment and orientation of submicroscopic features in label-free as well as fluorescently labeled speci ... Full text Link to item Cite

Ploidy variation in multinucleate cells changes under stress.

Journal Article Mol Biol Cell · March 15, 2015 Ploidy variation is found in contexts as diverse as solid tumors, drug resistance in fungal infection, and normal development. Altering chromosome or genome copy number supports adaptation to fluctuating environments but is also associated with fitness def ... Full text Link to item Cite

PolyQ-dependent RNA-protein assemblies control symmetry breaking.

Journal Article J Cell Biol · March 2, 2015 Dendritic growth in fungi and neurons requires that multiple axes of polarity are established and maintained within the same cytoplasm. We have discovered that transcripts encoding key polarity factors including a formin, Bni1, and a polarisome scaffold, S ... Full text Link to item Cite

Septins and Generation of Asymmetries in Fungal Cells.

Book · 2015 Polarized growth is critical for the development and maintenance of diverse organisms and tissues but particularly so in fungi, where nutrient uptake, communication, and reproduction all rely on cell asymmetries. To achieve polarized growth, fungi spatiall ... Full text Link to item Cite

Fungal pathogens are platforms for discovering novel and conserved septin properties.

Journal Article Curr Opin Microbiol · August 2014 Septins are filament-forming GTP-binding proteins that act as scaffolds in diverse cell functions including division, polarity and membrane remodeling. In a variety of fungal pathogens, it has been observed that septins are required for virulence because c ... Full text Link to item Cite

Cytoskeleton: cirque du septins.

Journal Article Curr Biol · June 2, 2014 Septins and F-actin are familiar cohabitants of the cleavage furrow yet how they might be functionally connected has been ambiguous. New work shows that septins can promote the assembly of curved bundles of F-actin, providing an unexpected molecular functi ... Full text Link to item Cite

Septin assemblies form by diffusion-driven annealing on membranes.

Journal Article Proc Natl Acad Sci U S A · February 11, 2014 Septins assemble into filaments and higher-order structures that act as scaffolds for diverse cell functions including cytokinesis, cell polarity, and membrane remodeling. Despite their conserved role in cell organization, little is known about how septin ... Full text Link to item Cite

Nuclear repulsion enables division autonomy in a single cytoplasm.

Journal Article Curr Biol · October 21, 2013 BACKGROUND: Current models of cell-cycle control, based on classic studies of fused cells, predict that nuclei in a shared cytoplasm respond to the same CDK activities to undergo synchronous cycling. However, synchrony is rarely observed in naturally occur ... Full text Link to item Cite

Protein aggregation behavior regulates cyclin transcript localization and cell-cycle control.

Journal Article Dev Cell · June 24, 2013 Little is known about the active positioning of transcripts outside of embryogenesis or highly polarized cells. We show here that a specific G1 cyclin transcript is highly clustered in the cytoplasm of large multinucleate cells. This heterogeneous cyclin t ... Full text Link to item Cite

Septin phosphorylation and coiled-coil domains function in cell and septin ring morphology in the filamentous fungus Ashbya gossypii.

Journal Article Eukaryot Cell · February 2013 Septins are a class of GTP-binding proteins conserved throughout many eukaryotes. Individual septin subunits associate with one another and assemble into heteromeric complexes that form filaments and higher-order structures in vivo. The mechanisms underlyi ... Full text Link to item Cite

Septin ring size scaling and dynamics require the coiled-coil region of Shs1p.

Journal Article Mol Biol Cell · September 2012 Septins are conserved GTP-binding proteins that assemble into heteromeric complexes that form filaments and higher-order structures in cells. What directs filament assembly, determines the size of higher-order septin structures, and governs septin dynamics ... Full text Link to item Cite

Heterogeneity in mitochondrial morphology and membrane potential is independent of the nuclear division cycle in multinucleate fungal cells.

Journal Article Eukaryot Cell · March 2012 In the multinucleate filamentous fungus Ashbya gossypii, nuclei divide asynchronously in a common cytoplasm. We hypothesize that the division cycle machinery has a limited zone of influence in the cytoplasm to promote nuclear autonomy. Mitochondria in cult ... Full text Link to item Cite

Spatial guidance of cell asymmetry: septin GTPases show the way.

Journal Article Traffic · February 2012 Eukaryotic cells develop asymmetric shapes suited for specific physiological functions. Morphogenesis of polarized domains and structures requires the amplification of molecular asymmetries by scaffold proteins and regulatory feedback loops. Small monomeri ... Full text Link to item Cite

Axl2 integrates polarity establishment, maintenance, and environmental stress response in the filamentous fungus Ashbya gossypii.

Journal Article Eukaryot Cell · December 2011 In budding yeast, new sites of polarity are chosen with each cell cycle and polarization is transient. In filamentous fungi, sites of polarity persist for extended periods of growth and new polarity sites can be established while existing sites are maintai ... Full text Link to item Cite

Rapid and quantitative imaging of excitation polarized fluorescence reveals ordered septin dynamics in live yeast.

Journal Article Biophys J · August 17, 2011 We report an imaging method for fast, sensitive analysis of the orientation of fluorescent molecules by employing a liquid-crystal based universal polarizer in the optical path of a wide-field light microscope. We developed specific acquisition and process ... Full text Link to item Cite

Septin filaments exhibit a dynamic, paired organization that is conserved from yeast to mammals.

Journal Article J Cell Biol · June 13, 2011 The septins are conserved, GTP-binding proteins important for cytokinesis, membrane compartmentalization, and exocytosis. However, it is unknown how septins are arranged within higher-order structures in cells. To determine the organization of septins in l ... Full text Link to item Cite

Guides to the final frontier of the cytoskeleton: septins in filamentous fungi.

Journal Article Curr Opin Microbiol · December 2010 Recent investigations have established core principles by which septins can form non-polar filaments in vitro. How cells then assemble, regulate and use septin polymers is still only beginning to be understood. It is clear that there is plasticity and vari ... Full text Link to item Cite

Physical interaction between VIVID and white collar complex regulates photoadaptation in Neurospora.

Journal Article Proc Natl Acad Sci U S A · September 21, 2010 Photoadaptation, the ability to attenuate a light response on prolonged light exposure while remaining sensitive to escalating changes in light intensity, is essential for organisms to decipher time information appropriately, yet the underlying molecular m ... Full text Link to item Cite

A conserved G₁ regulatory circuit promotes asynchronous behavior of nuclei sharing a common cytoplasm.

Journal Article Cell Cycle · September 15, 2010 Synthesis and accumulation of conserved cell cycle regulators such as cyclins are thought to promote G₁/S and G₂/M transitions in most eukaryotes. When cells at different stages of the cell cycle are fused to form heterokaryons, the shared complement of re ... Full text Link to item Cite

Cellular requirements for the small molecule forchlorfenuron to stabilize the septin cytoskeleton.

Journal Article Cytoskeleton (Hoboken) · June 2010 The septins are filament-forming, GTP-binding proteins that are conserved from yeast to humans. Septins assemble into higher-order structures such as rings, bars, and gauzes with diverse functions including serving as membrane diffusion barriers and scaffo ... Full text Link to item Cite

Dancing genomes: fungal nuclear positioning.

Journal Article Nat Rev Microbiol · December 2009 The many different mechanisms that fungi use to transmit and share genetic material are mediated by a broad range of chromosome and nuclear dynamics. The mechanics underlying nuclear migration are well integrated into detailed models, in which the forces s ... Full text Link to item Cite

Regulation of distinct septin rings in a single cell by Elm1p and Gin4p kinases.

Journal Article Mol Biol Cell · April 2009 Septins are conserved, GTP-binding proteins that assemble into higher order structures, including filaments and rings with varied cellular functions. Using four-dimensional quantitative fluorescence microscopy of Ashbya gossypii fungal cells, we show that ... Full text Link to item Cite

Pathocycles.

Journal Article Fungal Genet Biol · January 2008 Full text Link to item Cite

Identifying fungal regulatory motif patterns using SCOPE, an ensemble learning method motif finder

Conference Proceedings of the 7th IEEE International Conference on Bioinformatics and Bioengineering, BIBE · December 1, 2007 We reported previously on the development of SCOPE, an ensemble learning method motif finder. In this study, SCOPE was used to examine motif patterns for gene sets regulated by transcription factors MBF and SBF in Saccharomyces cerevisiae. Gene sets indivi ... Full text Cite

Limited functional redundancy and oscillation of cyclins in multinucleated Ashbya gossypii fungal cells.

Journal Article Eukaryot Cell · March 2007 Cyclin protein behavior has not been systematically investigated in multinucleated cells with asynchronous mitoses. Cyclins are canonical oscillating cell cycle proteins, but it is unclear how fluctuating protein gradients can be established in multinuclea ... Full text Link to item Cite

The anaphase-promoting complex/cyclosome is required for anaphase progression in multinucleated Ashbya gossypii cells.

Journal Article Eukaryot Cell · February 2007 Regulated protein degradation is essential for eukaryotic cell cycle progression. The anaphase-promoting complex/cyclosome (APC/C) is responsible for the protein destruction required for the initiation of anaphase and the exit from mitosis, including the d ... Full text Link to item Cite

Nuclear anarchy: asynchronous mitosis in multinucleated fungal hyphae.

Journal Article Curr Opin Microbiol · December 2006 Multinucleated cells are found in diverse contexts and include filamentous fungi, developing insect embryos, skeletal muscle and metastasizing tumor cells. Some multinucleated cells such as those in muscles arise from cell fusion events, but many are forme ... Full text Link to item Cite

AgSwe1p regulates mitosis in response to morphogenesis and nutrients in multinucleated Ashbya gossypii cells.

Journal Article Mol Biol Cell · October 2006 Nuclei in the filamentous, multinucleated fungus Ashbya gossypii divide asynchronously. We have investigated what internal and external signals spatially direct mitosis within these hyphal cells. Mitoses are most common near cortical septin rings found at ... Full text Link to item Cite

Control of filamentous fungal cell shape by septins and formins.

Journal Article Nat Rev Microbiol · March 2006 Studies in various model systems have identified two protein families that are crucial for shaping cell morphology: the septins and the formins. Both families are conserved in most eukaryotes, but the functions and regulation of individual homologues can v ... Full text Link to item Cite

Asynchronous nuclear division cycles in multinucleated cells.

Journal Article J Cell Biol · January 30, 2006 Synchronous mitosis is common in multinucleated cells. We analyzed a unique asynchronous nuclear division cycle in a multinucleated filamentous fungus, Ashbya gossypii. Nuclear pedigree analysis and observation of GFP-labeled spindle pole bodies demonstrat ... Full text Link to item Cite

Interplay between septin organization, cell cycle and cell shape in yeast.

Journal Article J Cell Sci · April 15, 2005 Septins are conserved filament-forming proteins that assemble into cortical cytoskeletal structures in animal and fungal cells. Although rapid progress has been made into the functions of septins, the mechanisms governing their localization and organizatio ... Full text Link to item Cite

Genetic interactions among regulators of septin organization.

Journal Article Eukaryot Cell · August 2004 Septins form a cortical scaffold at the yeast mother-bud neck that restricts the diffusion of cortical proteins between the mother and bud and serves as a signaling center that is important for governing various cell functions. After cell cycle commitment ... Full text Link to item Cite

Cdc42p, GTP hydrolysis, and the cell's sense of direction.

Journal Article Cell Cycle · July 2004 The GTPase Cdc42p is essential for polarity establishment in animals and fungi.(1) Human Cdc42p can functionally replace yeast Cdc42p,(2) indicating a high degree of evolutionary conservation. Current models of Cdc42p action generally follow the signaling ... Link to item Cite

Scaffold-mediated symmetry breaking by Cdc42p.

Journal Article Nat Cell Biol · December 2003 Cell polarization generally occurs along a single well-defined axis that is frequently determined by environmental cues such as chemoattractant gradients or cell-cell contacts, but polarization can also occur spontaneously in the apparent absence of such c ... Full text Link to item Cite

Septin ring assembly involves cycles of GTP loading and hydrolysis by Cdc42p.

Journal Article J Cell Biol · January 21, 2002 At the beginning of the budding yeast cell cycle, the GTPase Cdc42p promotes the assembly of a ring of septins at the site of future bud emergence. Here, we present an analysis of cdc42 mutants that display specific defects in septin organization, which id ... Full text Link to item Cite

The septin cortex at the yeast mother-bud neck.

Journal Article Curr Opin Microbiol · December 2001 A specialized cortical domain is organized by the septins at the necks of budding yeast cells. Recent findings suggest that this domain serves as a diffusion barrier and also as a local cell-shape sensor. We review these findings along with what is known a ... Full text Link to item Cite

Yeast Cdc42 functions at a late step in exocytosis, specifically during polarized growth of the emerging bud.

Journal Article J Cell Biol · November 12, 2001 The Rho family GTPase Cdc42 is a key regulator of cell polarity and cytoskeletal organization in eukaryotic cells. In yeast, the role of Cdc42 in polarization of cell growth includes polarization of the actin cytoskeleton, which delivers secretory vesicles ... Full text Link to item Cite

Yeast Cdc42 functions at a late step in exocytosis, specifically during polarized growth of the emerging bud

Journal Article Journal of Cell Biology · October 29, 2001 The Rho family GTPase Cdc42 is a key regulator of cell polarity and cytoskeletal organization in eukaryotic cells. In yeast, the role of Cdc42 in polarization of cell growth includes polarization of the actin cytoskeleton, which delivers secretory vesicles ... Full text Cite

Isolation and characterization of effector-loop mutants of CDC42 in yeast.

Journal Article Mol Biol Cell · May 2001 The highly conserved small GTPase Cdc42p is a key regulator of cell polarity and cytoskeletal organization in eukaryotic cells. Multiple effectors of Cdc42p have been identified, although it is unclear how their activities are coordinated to produce partic ... Full text Link to item Cite

Role of Cdc42p in pheromone-stimulated signal transduction in Saccharomyces cerevisiae.

Journal Article Mol Cell Biol · October 2000 CDC42 encodes a highly conserved GTPase of the Rho family that is best known for its role in regulating cell polarity and actin organization. In addition, various studies of both yeast and mammalian cells have suggested that Cdc42p, through its interaction ... Full text Link to item Cite