About

Beverly Errede is an Emeritus Professor of Biochemistry and Biophysics at the University of North Carolina at Chapel Hill. She holds a PhD from the University of California, San Diego. Her professional role is associated with the Department of Biochemistry and Biophysics, located at 120 Mason Farm Road, Chapel Hill, NC. The page provides her contact information, including an office phone number and email address, but does not include specific details about her research focus, background, or key contributions.

Research topics

• Cell biology
• Biology
• Genetics
• Biological system
• Computational biology
• Physics
• Biophysics
• Optoelectronics

Selected publications

• Multiscale Modeling of Bistability in the Yeast Polarity Circuit

  Cells · 2024-08-15 · 1 citations

  articleOpen access

  Cell polarity refers to the asymmetric distribution of proteins and other molecules along a specified axis within a cell. Polarity establishment is the first step in many cellular processes. For example, directed growth or migration requires the formation of a cell front and back. In many cases, polarity occurs in the absence of spatial cues. That is, the cell undergoes symmetry breaking. Understanding the molecular mechanisms that allow cells to break symmetry and polarize requires computational models that span multiple spatial and temporal scales. Here, we apply a multiscale modeling approach to examine the polarity circuit of yeast. In addition to symmetry breaking, experiments revealed two key features of the yeast polarity circuit: bistability and rapid dismantling of the polarity site following a loss of signal. We used modeling based on ordinary differential equations (ODEs) to investigate mechanisms that generate these behaviors. Our analysis revealed that a model involving positive and negative feedback acting on different time scales captured both features. We then extend our ODE model into a coarse-grained reaction-diffusion equation (RDE) model to capture the spatial profiles of polarity factors. After establishing that the coarse-grained RDE model qualitatively captures key features of the polarity circuit, we expand it to more accurately capture the biochemical reactions involved in the system. We convert the expanded model to a particle-based model that resolves individual molecules and captures fluctuations that arise from the stochastic nature of biochemical reactions. Our models assume that negative regulation results from negative feedback. However, experimental observations do not rule out the possibility that negative regulation occurs through an incoherent feedforward loop. Therefore, we conclude by using our RDE model to suggest how negative feedback might be distinguished from incoherent feedforward regulation.

  PublisherOA PDFDOI

• Multiscale Modeling of Bistability in the Yeast Polarity Circuit

  UNC Libraries · 2024-09-04

  articleOpen access

  Cell polarity refers to the asymmetric distribution of proteins and other molecules along a specified axis within a cell. Polarity establishment is the first step in many cellular processes. For example, directed growth or migration requires the formation of a cell front and back. In many cases, polarity occurs in the absence of spatial cues. That is, the cell undergoes symmetry breaking. Understanding the molecular mechanisms that allow cells to break symmetry and polarize requires computational models that span multiple spatial and temporal scales. Here, we apply a multiscale modeling approach to examine the polarity circuit of yeast. In addition to symmetry breaking, experiments revealed two key features of the yeast polarity circuit: bistability and rapid dismantling of the polarity site following a loss of signal. We used modeling based on ordinary differential equations (ODEs) to investigate mechanisms that generate these behaviors. Our analysis revealed that a model involving positive and negative feedback acting on different time scales captured both features. We then extend our ODE model into a coarse-grained reaction–diffusion equation (RDE) model to capture the spatial profiles of polarity factors. After establishing that the coarse-grained RDE model qualitatively captures key features of the polarity circuit, we expand it to more accurately capture the biochemical reactions involved in the system. We convert the expanded model to a particle-based model that resolves individual molecules and captures fluctuations that arise from the stochastic nature of biochemical reactions. Our models assume that negative regulation results from negative feedback. However, experimental observations do not rule out the possibility that negative regulation occurs through an incoherent feedforward loop. Therefore, we conclude by using our RDE model to suggest how negative feedback might be distinguished from incoherent feedforward regulation.

  PublisherDOI

• Constitutive mutants of the protein kinase STE11 activate the yeast pheromone response pathway in the absence of the G protein.

  UNC Libraries · 2021-07-02

  articleOpen access

  STE4 encodes the beta-subunit of a heterotrimeric guanine nucleotide-binding protein (G protein) that is an early and essential component of the pheromone signal transduction pathway. From a ste4 deletion strain we have isolated both dominant and recessive suppressors that show increased transcription of pheromone responsive genes and have regained the ability to mate, albeit at a low level. Each of these suppressor mutations suppresses ste4 and ste5 deletions but not deletions in STE7, STE11, or STE12. Among the dominant mutations, we have identified two alleles of STE11, a gene that encodes a protein kinase activity essential for mating. One allele contains an alteration in the putative regulatory domain of the protein kinase; the second allele has an alteration in the catalytic site. In strains carrying these mutations, a second protein kinase required for mating, STE7, becomes hyperphosphorylated, just as it does in wild-type cells treated with pheromone. Thus, a protein kinase cascade appears to be an essential feature of the response pathway and probably connects the receptor/G protein to an identified transcription factor, STE12.

  PublisherDOI

• Combined computational and experimental analysis reveals mitogen-activated protein kinase-mediated feedback phosphorylation as a mechanism for signaling specificity

  UNC Libraries · 2021-07-01

  articleOpen access

  A series of mathematical models was used to quantitatively characterize pheromone-stimulated kinase activation and determine how mitogen-activated protein (MAP) kinase specificity is achieved. The findings reveal how feedback phosphorylation of a common pathway component can limit the activity of a competing MAP kinase through feedback phosphorylation of a common activator, and thereby promote signal fidelity.Different environmental stimuli often use the same set of signaling proteins to achieve very different physiological outcomes. The mating and invasive growth pathways in yeast each employ a mitogen-activated protein (MAP) kinase cascade that includes Ste20, Ste11, and Ste7. Whereas proper mating requires Ste7 activation of the MAP kinase Fus3, invasive growth requires activation of the alternate MAP kinase Kss1. To determine how MAP kinase specificity is achieved, we used a series of mathematical models to quantitatively characterize pheromone-stimulated kinase activation. In accordance with the computational analysis, MAP kinase feedback phosphorylation of Ste7 results in diminished activation of Kss1, but not Fus3. These findings reveal how feedback phosphorylation of a common pathway component can limit the activity of a competing MAP kinase through feedback phosphorylation of a common activator, and thereby promote signal fidelity.

  PublisherDOI

• A predictive model of gene expression reveals the role of network motifs in the mating response of yeast

  Science Signaling · 2021 · 7 citations

  Senior authorCorresponding
  • Biology
  • Genetics
  • Computational biology

  exposed to different dynamic patterns of pheromone. We found that pheromone-induced transcription persisted after pheromone removal and showed long-term adaptation upon sustained pheromone exposure. We developed a model of the regulatory network that captured both characteristics of the mating response. We fit this model to experimental data with an evolutionary algorithm and used the parameterized model to predict scenarios for which it was not trained, including different temporal stimulus profiles and genetic perturbations to pathway components. Our model allowed us to establish the role of four architectural elements of the network in regulating gene expression. These network motifs are incoherent feedforward, positive feedback, negative feedback, and repressor binding. Experimental and computational perturbations to these network motifs established a specific role for each in coordinating the mating response to persistent and dynamic stimulation.

  PublisherOA PDFDOI

• STE11 is a protein kinase required for cell-type-specific transcription and signal transduction in yeast.

  UNC Libraries · 2021-07-02

  articleOpen access

  The STE11 gene of Saccharomyces cerevisiae is one of several genes required for mating between two haploid cell types of this yeast. Its product is required for response to a signal that causes arrest of the mitotic cell cycle in the G1 phase and induction of mating-type-specific genes. The nucleotide sequence of the STE11 gene was determined. The predicted amino acid sequence shows homology to the protein kinase family. We demonstrate that the STE11 product has kinase catalytic activity and that this activity is required for its in vivo functions.

  PublisherDOI

• Bistability in the polarity circuit of yeast

  Molecular Biology of the Cell · 2021 · 4 citations

  1st authorCorresponding
  • Biology
  • Biological system
  • Cell biology

  Cells polarize their growth or movement in many different physiological contexts. A key driver of polarity is the Rho GTPase Cdc42, which when activated becomes clustered or concentrated at polar sites. Multiple models for polarity establishment have been proposed. All of them rely on positive feedback to reinforce regions of high Cdc42 activity. Positive feedback can lead to bistability, a scenario in which cells can exist in either a polarized or unpolarized state under identical external conditions. Determining if the signaling circuit that drives Cdc42 polarity is bistable would provide important information about the mechanism that underlies polarity establishment and insights into the design features required for proper cellular function. We studied polarity establishment during the mating response of yeast. Using microfluidics to precisely control the temporal profile of mating pheromone and live-cell imaging to monitor the polarity process in single living cells, we found that the polarity circuit of yeast shows hysteresis, a characteristic feature of bistable systems. Our analysis also revealed that cells exposed to high pheromone concentrations rapidly lose polarity following a precipitous removal of pheromone. We used a reaction-diffusion model for polarity establishment to demonstrate that delayed negative regulation is sufficient to explain our experimental results. [Media: see text] [Media: see text] [Media: see text] [Media: see text].

  PublisherDOI

• Identification of Novel Pheromone-response Regulators through Systematic Overexpression of 120 Protein Kinases in Yeast

  UNC Libraries · 2021-07-03

  articleOpen accessSenior author

  Protein kinases are well known to transmit and regulate signaling pathways. To identify additional regulators of the pheromone signaling apparatus in yeast, we evaluated an array of 120 likely protein kinases encoded by the yeast genome. Each kinase was fused to glutathione S-transferase, overexpressed, and tested for changes in pheromone responsiveness in vivo. As expected, several known components of the pathway (YCK1, STE7, STE11, FUS3, and KSS1) impaired the growth arrest response. Seven other kinases also interfered with pheromone-induced growth arrest; in rank order they are as follows: YKL116c (renamed PRR1) = YDL214c (renamed PRR2) > YJL141c (YAK1, SRA1) > YNR047w = YCR091w (KIN82) = YIL095w (PRK1) > YCL024w (KCC4). Inhibition of pheromone signaling by PRR1, but not PRR2, required the glutathione S-transferase moiety. Both kinases inhibited gene transcription after stimulation with pheromone, a constitutively active kinase mutant STE11-4, or overexpression of the transcription factor STE12. Neither protein altered the ability of the mitogen-activated protein kinase (MAPK) Fus3 to feedback phosphorylate a known substrate, the MAPK kinase Ste7. These results reveal two new components of the pheromone-signaling cascade in yeast, each acting at a point downstream of the MAPK.

  PublisherDOI

• Ash1, a Daughter Cell-Specific Protein, Is Required for Pseudohyphal Growth ofSaccharomyces cerevisiae

  UNC Libraries · 2020-11-06

  articleOpen access1st authorCorresponding

  Ash1 (for asymmetric synthesis ofHO) was first uncovered in genetic screens that revealed its role in mating-type switching. Ash1 preventsHOexpression in daughter cells. Because Ash1 has a zinc finger-like domain related to that of the GATA family of transcription factors, it presumably acts by repressingHOtranscription. Nonswitching diploid cells also express Ash1, suggesting it could have functions in addition to regulation ofHOexpression. We show here that Ash1 has an essential function for pseudohyphal growth. Our epistasis analyses are consistent with the deduction that Ash1 acts separately from the mitogen-activated protein kinase cascade and Ste12. Similarly to the case in yeast form cells, Ash1 is asymmetrically localized to the nuclei of daughter cells during pseudohyphal growth. This asymmetric localization reveals that there is a previously unsuspected daughter cell-specific function necessary for pseudohyphal growth.

  PublisherDOI

• Regulation of Cell Signaling Dynamics by the Protein Kinase-Scaffold Ste5

  UNC Libraries · 2020-11-06 · 2 citations

  articleOpen access

  Cell differentiation requires the ability to detect and respond appropriately to a variety of extracellular signals. Here we investigate a differentiation switch induced by changes in the concentration of a single stimulus. Yeast cells exposed to high doses of mating pheromone undergo cell division arrest. Cells at intermediate doses become elongated and divide in the direction of a pheromone gradient (chemotropic-growth). Either of the pheromone-responsive MAP kinases, Fus3 and Kss1, promotes cell elongation, but only Fus3 promotes chemotropic growth. Whereas Kss1 is activated rapidly and with a graded dose-response profile, Fus3 is activated slowly and exhibits a steeper dose-response relationship (ultrasensitivity). Fus3 activity requires the scaffold protein Ste5; when binding to Ste5 is abrogated Fus3 behaves like Kss1, and the cells no longer respond to a gradient or mate efficiently with distant partners. We propose that scaffold proteins serve to modulate the temporal and dose-response behavior of the MAP kinase.

  PublisherDOI

Recent grants

• NIH Grant R01GM030619

  NIH · $1.3M · 1994

• NIH Grant R01GM079271

  NIH · $4.0M · 2019

• Mechanisms of noise regulation in cell fate transitions

  NIH · $2.1M · 2015–2019

• NIH Grant R01GM084071

  NIH · $1.4M · 2013

• NIH Grant R01GM039852

  NIH · $2.9M · 2004

Frequent coauthors

• Timothy C. Elston

  University of North Carolina at Chapel Hill

  23 shared

• Henrik Dohlman

  17 shared

• M Company

  17 shared

• R. Keith Esch

  University of Hagen

  11 shared

• Malcolm Whiteway

  Concordia University

  9 shared

• Melinda Baur

  9 shared

• Siarhei Hladyshau

  Georgia Institute of Technology

  7 shared

• Denis Tsygankov

  Georgia Institute of Technology

  7 shared

Labs

• Beverly Errede LabPI

Education

• Ph.D.

  University of California, San Diego