2. Academic Validation
  3. Genetically encoded fluorescent reporter for polyamines

Genetically encoded fluorescent reporter for polyamines

  • bioRxiv. 2024 Nov 17:2024.08.24.609500. doi: 10.1101/2024.08.24.609500.
Pushkal Sharma 1 2,  Colin Y Kim 1 3 4,  Heather R Keys 1,  Shinya Imada 5,  Alex B Joseph 1,  Luke Ferro 1,  Tenzin Kunchok 1,  Rachel Anderson 1 6,  Omer Yilmaz 5 6,  Jing-Ke Weng 1 7 8,  Ankur Jain 1 6
Affiliations

Affiliations

  • 1 Whitehead Institute of Biomedical Research, Cambridge, MA, USA.
  • 2 Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • 3 Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • 4 Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA, USA.
  • 5 The David H. Koch Institute for Integrative Cancer Research at MIT, Cambridge, MA, USA.
  • 6 Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • 7 Institute for Plant-Human Interface, Northeastern University, Boston, MA, USA.
  • 8 Department of Chemistry and Chemical Biology, Department of Bioengineering and Department of Chemical Engineering, Northeastern University, Boston, MA, USA.
PMID: 39253442 DOI: 10.1101/2024.08.24.609500
Abstract

Polyamines are abundant and evolutionarily conserved metabolites that are essential for life. Dietary polyamine supplementation extends life-span and health-span. Dysregulation of polyamine homeostasis is linked to Parkinson's disease and Cancer, driving interest in therapeutically targeting this pathway. However, measuring cellular polyamine levels, which vary across cell types and states, remains challenging. We introduce a first-in-class genetically encoded polyamine reporter for real-time measurement of polyamine concentrations in single living cells. This reporter utilizes the polyamine-responsive ribosomal frameshift motif from the OAZ1 gene. We demonstrate broad applicability of this approach and reveal dynamic changes in polyamine levels in response to genetic and pharmacological perturbations. Using this reporter, we conducted a genome-wide CRISPR screen and uncovered an unexpected link between mitochondrial respiration and polyamine import, which are both risk factors for Parkinson's disease. By offering a new lens to examine polyamine biology, this reporter may advance our understanding of these ubiquitous metabolites and accelerate therapy development.

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