Molecular imaging with engineered physiology

Desai, Mitul; Slusarczyk, Adrian L.; Chapin, Ashley A.; Barch, Mariya; Jasanoff, Alan

doi:10.1038/ncomms13607

Cited by 37 publications

(40 citation statements)

References 54 publications

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“…For example, it has recently been reported that changes in vascular flow in parenchymal arterioles can alter pyramidal neuron activity in cortical slices . And conversely, centrally released CGRP can also alter in vivo blood flow deep in the brain . It is intriguing to speculate that these mechanisms might allow communication between peripheral and central CGRP actions in migraine.…”

Section: Modulation In the Brain And Peripherymentioning

confidence: 99%

“…33 And conversely, centrally released CGRP can also alter in vivo blood flow deep in the brain. 34 It is intriguing to speculate that these mechanisms might allow communication In this scenario, the neuropeptide from neuron 3 has enhanced the EPSP caused by the neurotransmitter from neuron 1. The nonmodulated EPSP from neuron 1 alone is shown as a solid line and the EPSP following stimulation of neurons 1 and 3 is shown as the dashed line.…”

Section: Modulation In the Brain And Peripherymentioning

confidence: 99%

See 1 more Smart Citation

Overview of Neuropeptides: Awakening the Senses?

2017

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Humans have a diverse collection of neuropeptides that can influence a multitude of activities. There are now over 100 known neuropeptides and probably many more yet to be identified from the over 1000 predicted peptides encoded by the genome. While diverse, peptides generally share three common characteristics: (1) post-translational processing and release from vesicles, (2) activation of cell-surface receptors over a relatively large distance, and (3) modulation of target cells that are often in the brain and periphery. Within the brain, neuropeptides can modulate the activity of co-released neurotransmitters to either increase or decrease the strength of synaptic signaling. Within the periphery, neuropeptides can function similar to peptide hormones and modulate nearly all bodily functions. Given the clear involvement of the neuropeptide CGRP in migraine and the emerging evidence for other peptides, it seems likely that neuropeptides may help “awaken” the senses and contribute to the heightened sensory state of migraine.

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Section: Modulation In the Brain And Peripherymentioning

confidence: 99%

Section: Modulation In the Brain And Peripherymentioning

confidence: 99%

Overview of Neuropeptides: Awakening the Senses?

2017

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“…Another recently introduced mechanism for biomolecular MRI involves peptides that act on smooth muscle cells to increase blood flow locally, resulting in blood oxygenation level dependent (BOLD) contrast [101] (Fig. 1g).…”

Section: Emerging Mechanisms Of Biomolecular Mri: Diffusion Hypermentioning

confidence: 99%

“…However, unlike most other amplified reporters, no external administration of contrast agents is required, and kinetics can be rapid, since the blood flow can increase and decrease on a second timescale in response to appropriate signals. Furthermore, CGRP can be engineered as a molecular sensor, for example by incorporating autoinhibitory domains that become cleaved by proteases [101]. …”

Section: Emerging Mechanisms Of Biomolecular Mri: Diffusion Hypermentioning

confidence: 99%

Biomolecular MRI reporters: Evolution of new mechanisms

Mukherjee

Davis

Ramesh

et al. 2017

Progress in Nuclear Magnetic Resonance Spectroscopy

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Magnetic resonance imaging (MRI) is a powerful technique for observing the function of specific cells and molecules inside living organisms. However, compared to optical microscopy, in which fluorescent protein reporters are available to visualize hundreds of cellular functions ranging from gene expression and chemical signaling to biomechanics, to date relatively few such reporters are available for MRI. Efforts to develop MRI-detectable biomolecules have mainly focused on proteins containing or transporting paramagnetic metals for T1 and T2 relaxation enhancement or large numbers of exchangeable protons for chemical exchange saturation transfer. While these pioneering developments established several key uses of biomolecular MRI, such as imaging of gene expression and functional biosensing, they also revealed that low molecular sensitivity poses a major challenge for broader adoption in biology and medicine. Recently, new classes of biomolecular reporters have been developed based on alternative contrast mechanisms, including enhancement of spin diffusivity, interactions with hyperpolarized nuclei, and modulation of blood flow. These novel reporters promise to improve sensitivity and enable new forms of multiplexed and functional imaging.

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“…Pioneering examples include enzymes that alter the relaxivity of gadolinium chelates 39 , human iron storage and transport genes such as ferritin 40, 41 and transferrin 42 , and natural and engineered proteins with large numbers of chemically labile protons for chemical exchange saturation transfer (CEST) imaging 43–48 . Recent developments have also included reporter genes causing accumulation of MRI-detectable compounds 49 , proteins interacting with hyperpolarized molecules 50, 51 , channels that alter the diffusion of water across cell membranes 52, 53 and vasodilators altering hemodynamic signals 54 . Several of these reporter genes are covered in detail in previous review articles 55–57 .…”

Section: Main Textmentioning

confidence: 99%

Molecular Imaging in Synthetic Biology, and Synthetic Biology in Molecular Imaging

Gilad

Shapiro

2017

Mol Imaging Biol

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Biomedical synthetic biology is an emerging field in which cells are engineered at the genetic level to carry out novel functions with relevance to biomedical and industrial applications. This approach promises new treatments, imaging tools and diagnostics for diseases ranging from gastrointestinal inflammatory syndromes to cancer, diabetes and neurodegeneration. As these cellular technologies undergo pre-clinical and clinical development, it is becoming essential to monitor their location and function in vivo, necessitating appropriate molecular imaging strategies, and therefore we have created an Interest Group within the World Molecular Imaging Society focusing on synthetic biology and reporter gene technologies. Here, we highlight recent advances in biomedical synthetic biology, including bacterial therapy, immunotherapy and regenerative medicine. We then discuss emerging molecular imaging approaches to facilitate in vivo applications, focusing on reporter genes for noninvasive modalities such as magnetic resonance, ultrasound, photoacoustic imaging, bioluminescence and radionuclear imaging. Because reporter genes can be incorporated directly into engineered genetic circuits, they are particularly well suited to imaging synthetic biological constructs, and developing them provides opportunities for creative molecular and genetic engineering.

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Molecular imaging with engineered physiology

Cited by 37 publications

References 54 publications

Overview of Neuropeptides: Awakening the Senses?

Overview of Neuropeptides: Awakening the Senses?

Biomolecular MRI reporters: Evolution of new mechanisms

Molecular Imaging in Synthetic Biology, and Synthetic Biology in Molecular Imaging

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