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PreprintCC BYbioRxiv

PRISM: A Plasmid-based Reporter for Intracellular Spectral Microscopy

  1. 1Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK, CB2 0XY

Abstract

Organelles form an interconnected network whose morphology, positioning and interactions reflect cellular state. However, reproducibly quantifying these organelle phenotypes across large cell populations and diverse cell types remains a significant challenge. Here we present PRISM (Plasmid-based Reporter for Intracellular Spectral Microscopy), a PiggyBac-integrable construct encoding five unique fluorescent organelle reporters for spectral microscopy, with an accompanying modular analysis pipeline. PRISM stably labels the Golgi, peroxisomes, endoplasmic reticulum, mitochondria and lysosomes in multiple cell types while remaining compatible with additional molecular or functional probes. The workflow extracts over 500 metrics per cell, describing organelle morphology and distribution alongside pairwise and higher-order contacts. We use PRISM to characterise organelle responses to cytoskeletal perturbation, map PI(4)P redistribution during lysosomal damage, and reveal how Zika virus remodels the organelle landscape during infection. PRISM provides a reproducible approach for investigating organelle network remodelling across biological contexts

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BibTeX
@misc{love2026prism,
  title = {{PRISM: A Plasmid-based Reporter for Intracellular Spectral Microscopy}},
  author = {F. M. Love and Z. Baskir and T. Allen and S. Thomas and H. Coyle and N. Al-Dam and S. Williams and H. Maib and N. Irigoyen and J. Nixon-Abell},
  howpublished = {bioRxiv},
  year = {2026},
  month = sep,
  doi = {10.64898/2026.09.01.746207},
  url = {https://www.biorxiv.org/content/10.64898/2026.09.01.746207v1},
  note = {CC BY},
}
RIS
TY  - UNPB
TI  - PRISM: A Plasmid-based Reporter for Intracellular Spectral Microscopy
AU  - F. M. Love
AU  - Z. Baskir
AU  - T. Allen
AU  - S. Thomas
AU  - H. Coyle
AU  - N. Al-Dam
AU  - S. Williams
AU  - H. Maib
AU  - N. Irigoyen
AU  - J. Nixon-Abell
PY  - 2026
DA  - 2026/09/01
PB  - bioRxiv
DO  - 10.64898/2026.09.01.746207
UR  - https://www.biorxiv.org/content/10.64898/2026.09.01.746207v1
AB  - Organelles form an interconnected network whose morphology, positioning and interactions reflect cellular state. However, reproducibly quantifying these organelle phenotypes across large cell populations and diverse cell types remains a significant challenge. Here we present PRISM (Plasmid-based Reporter for Intracellular Spectral Microscopy), a PiggyBac-integrable construct encoding five unique fluorescent organelle reporters for spectral microscopy, with an accompanying modular analysis pipeline. PRISM stably labels the Golgi, peroxisomes, endoplasmic reticulum, mitochondria and lysosomes in multiple cell types while remaining compatible with additional molecular or functional probes. The workflow extracts over 500 metrics per cell, describing organelle morphology and distribution alongside pairwise and higher-order contacts. We use PRISM to characterise organelle responses to cytoskeletal perturbation, map PI(4)P redistribution during lysosomal damage, and reveal how Zika virus remodels the organelle landscape during infection. PRISM provides a reproducible approach for investigating organelle network remodelling across biological contexts
ER  -