Exploring the potential of water channels for developing genetically encoded reporters and biosensors for diffusion-weighted MRI
Year: 2024
Type: article
Abstract: Genetically encoded reporters for magnetic resonance imaging (MRI) offer a valuable technology for making molecular-scale measurements of biological processes within living organisms with high anatomical resolution and whole-organ coverage without relying on ionizing radiation. However, most MRI reporters rely on synthetic contrast agents, typically paramagnetic metals and metal complexes, which often need to be supplemented exogenously to create optimal contrast. To eliminate the need for synthetic contrast agents, we previously introduced aquaporin-1, a mammalian water channel, as a new reporter gene for the fully autonomous detection of genetically labeled cells using diffusion-weighted MRI. In this study, we aimed to expand the toolbox of diffusion-based genetic reporters by modulating aquaporin membrane trafficking and harnessing the evolutionary diversity of water channels across species. We identified a number of new water channels that functioned as diffusion-weighted reporter genes. In addition, we show that loss-of-function variants of yeast and human aquaporins can be leveraged to design first-in-class diffusion-based sensors for detecting the activity of a model protease within living cells.
Source: Journal of Magnetic Resonance
Institution: University of California, Santa Barbara
Language: English
Subfield: Radiology, Nuclear Medicine and Imaging
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,660
Funders: National Science Foundation, National Institutes of Health, University of California, Santa Barbara, Materials Research Science and Engineering Center, Harvard University, National Institute on Drug Abuse, National Institute of General Medical Sciences, National Institute of Neurological Disorders and Stroke, National Institute of Biomedical Imaging and Bioengineering, Division of Materials Research, California NanoSystems Institute, Army Research Office, Institute for Collaborative Biotechnologies
Awards: G1141670404, G2232042528, Materials Research Science and Engineering Center at UCSB, G321649331, G401861217, A genetically encoded MRI reporter for noninvasive imaging of activity-dependent gene expression in neurons, G4281768896, G4950536974, G5681652957, G608057831, G65411870, G6569974432, G7400121136, G7452299184, G8415477955, Engineering fluorescence and magnetic resonance reporter genes for imaging biological function in hypoxic cells and in vivo, Engineering a calcium reporter gene for magnetic resonance imaging of neural activity, Metal-free, genetically encoded reporters for calcium recording with MRI
OpenAlex ID: W4400768531