Academic Appointments


  • Basic Life Science Research Associate, Biology

Journal Articles


  • Feedforward Regulation Ensures Stability and Rapid Reversibility of a Cellular State MOLECULAR CELL Doncic, A., Skotheim, J. M. 2013; 50 (6): 856-868

    Abstract

    Cellular transitions are important for all life. Such transitions, including cell fate decisions, often employ positive feedback regulation to establish and stabilize new cellular states. However, positive feedback is unlikely to underlie stable cell-cycle arrest in yeast exposed to mating pheromone because the signaling pathway is linear, rather than bistable, over a broad range of extracellular pheromone concentration. We show that the stability of the pheromone-arrested state results from coherent feedforward regulation of the cell-cycle inhibitor Far1. This network motif is effectively isolated from the more complex regulatory network in which it is embedded. Fast regulation of Far1 by phosphorylation allows rapid cell-cycle arrest and reentry, whereas slow Far1 synthesis reinforces arrest. We expect coherent feedforward regulation to be frequently implemented at reversible cellular transitions because this network motif can achieve the ostensibly conflicting aims of arrest stability and rapid reversibility without loss of signaling information.

    View details for DOI 10.1016/j.molcel.2013.04.014

    View details for Web of Science ID 000321319900009

  • An Algorithm to Automate Yeast Segmentation and Tracking PLOS ONE Doncic, A., Eser, U., Atay, O., Skotheim, J. M. 2013; 8 (3)
  • An algorithm to automate yeast segmentation and tracking. PloS one Doncic, A., Eser, U., Atay, O., Skotheim, J. M. 2013; 8 (3)

    Abstract

    Our understanding of dynamic cellular processes has been greatly enhanced by rapid advances in quantitative fluorescence microscopy. Imaging single cells has emphasized the prevalence of phenomena that can be difficult to infer from population measurements, such as all-or-none cellular decisions, cell-to-cell variability, and oscillations. Examination of these phenomena requires segmenting and tracking individual cells over long periods of time. However, accurate segmentation and tracking of cells is difficult and is often the rate-limiting step in an experimental pipeline. Here, we present an algorithm that accomplishes fully automated segmentation and tracking of budding yeast cells within growing colonies. The algorithm incorporates prior information of yeast-specific traits, such as immobility and growth rate, to segment an image using a set of threshold values rather than one specific optimized threshold. Results from the entire set of thresholds are then used to perform a robust final segmentation.

    View details for DOI 10.1371/journal.pone.0057970

    View details for PubMedID 23520484

  • Distinct Interactions Select and Maintain a Specific Cell Fate MOLECULAR CELL Doncic, A., Falleur-Fettig, M., Skotheim, J. M. 2011; 43 (4): 528-539

    Abstract

    The ability to specify and maintain discrete cell fates is essential for development. However, the dynamics underlying selection and stability of distinct cell types remain poorly understood. Here, we provide a quantitative single-cell analysis of commitment dynamics during the mating-mitosis switch in budding yeast. Commitment to division corresponds precisely to activating the G1 cyclin positive feedback loop in competition with the cyclin inhibitor Far1. Cyclin-dependent phosphorylation and inhibition of the mating pathway scaffold Ste5 are required to ensure exclusive expression of the mitotic transcriptional program after cell cycle commitment. Failure to commit exclusively results in coexpression of both cell cycle and pheromone-induced genes, and a morphologically mixed inviable cell fate. Thus, specification and maintenance of a cellular state are performed by distinct interactions, which are likely a consequence of disparate reaction rates and may be a general feature of the interlinked regulatory networks responsible for selecting cell fates.

    View details for DOI 10.1016/j.molcel.2011.06.025

    View details for Web of Science ID 000294151000006

    View details for PubMedID 21855793