About

The Hauf lab at Virginia Tech studies principles of faithful chromosome segregation and cell division, using fission yeast (S. pombe) as a model.

Research topics

• Computer Science
• Biology
• Cell biology
• Genetics
• Artificial Intelligence
• Physics
• Statistical physics
• Biological system
• Computer vision
• Optics
• Mathematics

Selected publications

• Chromosome segregation synchrony in <i>S. pombe</i> is noise-limited and arises without positive feedback

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-03-09

  articleOpen accessSenior authorCorresponding

  Anaphase is a key cell cycle transition that ensures faithful genome inheritance. At anaphase onset, sister chromatids separate abruptly and synchronously upon activation of the protease separase. Major cell cycle transitions often involve positive feedback, which contributes to their abruptness and irreversibility; however, whether such feedback is required for anaphase remains unclear. Here, we analyze sister chromatid separation dynamics in fission yeast using high-resolution live-cell imaging and computational modeling. We find that anaphase synchrony relies on fast degradation of the separase inhibitor securin, but does not require separase-mediated positive feedback. Hence, sister chromatid separation, being inherently irreversible, may be one of the few major cell cycle transitions that can proceed without positive feedback. A stochastic model fitted to the data revealed that separation synchrony is limited by stochasticity resulting from small-number effects. Together, these results support a feedback-independent mechanism for anaphase onset and identify molecular noise as a fundamental constraint on its temporal precision.

  PublisherOA PDFDOI

• eLife Assessment: Contractile peri-nuclear actomyosin network repositions peripheral and polar chromosomes to promote early kinetochore–microtubule interactions

  2026-03-03

  peer-reviewOpen access1st authorCorresponding

  For correct segregation of chromosomes in mitosis, they must efficiently and properly interact with the mitotic spindle during prometaphase. For this, the locations of chromosomes in the nucleus or relative to spindle poles are crucial – chromosomes at the nuclear periphery or behind spindle poles (polar regions) interact less efficiently with the mitotic spindle and show higher risks of missegregation in the subsequent anaphase. Nonetheless, the missegregation rate of such chromosomes is still relatively low in unperturbed normal cells. Thus, unknown mechanisms may mitigate the risks of their missegregation. We previously found that the actomyosin network (PANEM) is formed on the cytoplasmic side of the nuclear envelope during prophase, and its myosin-II-dependent contraction facilitates chromosome interaction with the mitotic spindle, shortly after nuclear envelope breakdown (NEBD). However, it remains unclear which chromosome interaction steps are facilitated or which chromosomes specifically benefit from it. Here, we show that the PANEM contraction directly pushes chromosomes located at the nuclear periphery inward immediately after NEBD. Tracking motions of individual kinetochores reveals that the PANEM contraction facilitates kinetochores’ initial interaction with spindle microtubules, but does not affect their subsequent poleward motion. The PANEM contraction also promotes the onset of their congression towards the spindle mid-plane, but does not affect congression itself once it starts. Furthermore, the PANEM contraction reduces the volume of polar regions, and helps reposition chromosomes from these regions and initiate their congression. Impaired PANEM contraction results in defective chromosome congression and frequent chromosome missegregation. In conclusion, shortly after NEBD, the PANEM contraction repositions chromosomes from unfavorable locations, i.e. the nuclear periphery and polar regions, to facilitate productive kinetochore-microtubule interaction and ensure high-fidelity chromosome segregation.

  PublisherDOI

• Chromosome segregation synchrony in <i>S. pombe</i> is noise limited and arises without positive feedback

  The Journal of Cell Biology · 2026-04-18

  articleOpen accessSenior author

  Anaphase is a key cell cycle transition that ensures faithful genome inheritance. At anaphase onset, sister chromatids separate abruptly and synchronously upon activation of the protease separase. Major cell cycle transitions often involve positive feedback, which contributes to their abruptness and irreversibility; however, whether such feedback is required for anaphase remains unclear. Here, we analyze sister chromatid separation dynamics in fission yeast using high-resolution live-cell imaging and computational modeling. We find that anaphase synchrony relies on fast degradation of the separase inhibitor securin but does not require separase-mediated positive feedback. Hence, sister chromatid separation, being inherently irreversible, may be one of the few major cell cycle transitions that can proceed without positive feedback. A stochastic model fitted to the data revealed that separation synchrony is limited by stochasticity resulting from small-number effects. Together, these results support a feedback-independent mechanism for anaphase onset and identify molecular noise as a fundamental constraint on its temporal precision.

  PublisherDOI

• Chromosome segregation synchrony in S. pombe is noise-limited and arises without positive feedback – Source data (experiment and stochastic simulation separation times)

  Zenodo (CERN European Organization for Nuclear Research) · 2026-04-07

  datasetOpen access

  Experimental_data: values for measured sister chromatid separation time differences; data is for all genotypes/conditions shown in main figures.Simulation_data: values for simulated sister chromatid separation time differences; data corresponds to Figure S5A. Please see columnExplanations sheet in each file for details.

  PublisherDOI

• Love-thy-neighbor: neural networks for tracking and lineage tracing in budding yeast

  Bioinformatics Advances · 2026-01-01 · 1 citations

  articleOpen access

  Tracking and lineage tracing are widely needed tasks in biological image analysis. For cells that grow and divide, tracking is challenging because cells change in number, shape, and size throughout a recording. Longer intervals between images make tracking more difficult. Consequently, tracking has to be performed between consecutive or temporally close images, which leads to exponentially decreasing tracking accuracy and high sensitivity to error rates. For budding yeast, this challenge is further heightened by the similarity of cells in colonies, their dense packing, asymmetric cell divisions, and movement due to colony growth. A related task, lineage tracing, is similarly challenging without fluorescent markers since a new daughter cell can be surrounded by multiple potential mother cells. Here, we present neural networks for budding yeast tracking and lineage tracing, named LYN-track and LYN-trace, respectively, which leverage fine geometric features of cells and their neighborhoods. To train and test the algorithms, we recorded and annotated budding and fission yeast timelapse microscopy movies (78 852 frame-to-frame tracklets, 2512 images), which we make available. On these and existing datasets, our neural network-based methods demonstrate robust, above state-of-the-art performance. Both tools are integrated into graphical user interfaces (GUIs) and can be retrained with custom data.

  PublisherDOI

• Love-thy-neighbor: Neural networks for tracking and lineage tracing in budding yeast

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-01-09

  articleOpen access

  Tracking and lineage tracing are widely needed tasks in biological image analysis. For cells that grow and divide, tracking is challenging because cells change in number, shape, and size throughout a recording. As the time interval between images increases, it becomes more difficult to establish correspondences between cells across timepoints. Consequently, tracking has to be performed between consecutive or temporally close images, which leads to exponentially decreasing tracking accuracy and thus high sensitivity to error rates. For budding yeast, this challenge is further heightened by the similarity of cells in colonies, their dense packing, the asymmetric nature of cell divisions, and movement due to growth of the colony. A related task, lineage tracing, is similarly challenging without fluorescent markers due to multiple potential mother cells surrounding a new daughter cell. Here, we present neural networks for budding yeast tracking and lineage tracing, named LYN-track and LYN-trace, respectively. These methods leverage fine geometric features of cells and their neighborhoods. To train and test the algorithms, we recorded and annotated new budding and fission yeast microscopy movies (78,852 frame-to-frame tracklets, 2,512 images), which we make freely available. On these and existing datasets, our neural network-based methods demonstrate robust, above state-of-the-art performance. Both tools have been integrated into graphical user interfaces (GUIs), available on Github, and can be straightforwardly retrained with custom data if desired.

  PublisherOA PDFDOI

• eLife Assessment: Geometry shapes cytoplasmic Cdk1 waves that drive cortical dynamics

  2026-05-05

  peer-reviewOpen access1st authorCorresponding

  Cell division in large embryos is coordinated by spatial waves of Cyclin B–Cdk1 activity that spread through the cytoplasm and affect cortical contractility. However, it is still unclear how cell size and localized activation near the nucleus shape these waves, and how the cytoplasmic signal is transmitted to the cortex. Here, we develop a reaction–diffusion model of Cyclin B–Cdk1 signaling in spherical cells with localized nuclear activation. We find that cytoplasmic waves have two distinct parts: an activation front that travels as a trigger wave, and a wave back that is controlled by inhibitory gradients in the cell cycle oscillator. Because these two parts are generated by different mechanisms, they can move at different speeds or even in opposite directions. This gives rise to different wave behaviors depending on nuclear size, nuclear position, and effective cell size. We then couple the Cdk1 signal to a cortical excitable network and show how cytoplasmic waveforms can regulate Rho–actin reactivation through inhibition of the RhoGEF Ect2. In this model, cortical patterns emerge mainly as downstream responses to cytoplasmic signaling, rather than as self-organized cortical waves. Overall, our results provide a mechanistic framework linking localized nuclear activation, cytoplasmic cell cycle waves, and cortical responses in large embryonic cells.

  PublisherDOI

• Chromosome segregation synchrony in S. pombe is noise-limited and arises without positive feedback – Source data (experiment and stochastic simulation separation times)

  Zenodo (CERN European Organization for Nuclear Research) · 2026-04-07

  datasetOpen access

  Experimental_data: values for measured sister chromatid separation time differences; data is for all genotypes/conditions shown in main figures.Simulation_data: values for simulated sister chromatid separation time differences; data corresponds to Figure S5A. Please see columnExplanations sheet in each file for details.

  PublisherDOI

• Establishing MS2-MCP-based single-molecule RNA visualization in <i>Schizosaccharomyces pombe</i>

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-03-09

  articleOpen accessSenior authorCorresponding

  Abstract Single-molecule RNA imaging using the MS2–MCP system has transformed the study of RNA biology across model organisms. However, this technology has remained unavailable for fission yeast (Schizosaccharomyces pombe) , even though fission yeast is a central model for eukaryotic gene expression. Achieving single-molecule sensitivity requires identifying a narrow optimum where RNA labels are sufficiently bright while background fluorescence remains minimal. We have now accomplished this for S. pombe by systematically optimizing MCP expression and localization—screening a panel of constitutive S. pombe promoters and evaluating combinations of nuclear localization and export signals (NLSs and NESs). The resulting, successful constructs use tandem StayGold as the MCP fluorescent tag, taking advantage of its superior photostability. Together with optimized vectors for MS2 stem-loop tagging of endogenous transcripts, these tools enable single-molecule RNA imaging in fission yeast, opening the door to quantitative analyses of RNA dynamics in this core genetic model.

  PublisherOA PDFDOI

• eLife Assessment: Gene expression variation across genetically identical individuals predicts reproductive traits

  2025-09-02

  peer-reviewOpen access1st authorCorresponding
  PublisherDOI

Recent grants

• The quantitative landscape of the mitotic checkpoint: from genes to function

  NSF · $540k · 2016–2020

• Molecular mechanisms of cell division robustness

  NIH · $1.8M · 2016–2023

Frequent coauthors

• Julia Kamenz

  University of Groningen

  24 shared

• André Koch

  University Children's Hospital Tübingen

  22 shared

• Stephanie Heinrich

  ETH Zurich

  21 shared

• Hanna Windecker

  Friedrich Miescher Laboratory

  13 shared

• Maria Langegger

  Max Planck Society

  13 shared

• Kenneth E. Sawin

  University of Edinburgh

  12 shared

• Claudia C. Bicho

  University of Edinburgh

  12 shared

• Yoshinori Watanabe

  12 shared

Labs

• Hauf LabPI

Awards & honors

• Virginia Tech Sally Bohland Award for Exceptional Leadership…
• Outstanding Service Award, Department of Biological Sciences…
• Outstanding Teaching Award, Department of Biological Science…
• Outstanding Research Award, Department of Biological Science…
• FASEB Travel Award (2012)