Sarah Bricault

Massachusetts Institute of Technology

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Alan Jasanoff

Massachusetts Institute of Technology

Mitul Desai

Massachusetts Institute of Technology

Felix Sigmund

Helmholtz Zentrum München

Gil G. Westmeyer

Helmholtz Zentrum München

Christoph Massner

University of Stuttgart

Albert J. R. Heck

Utrecht University

Tobias P. Wörner

Thermo Fisher Scientific (Germany)

Jürgen M. Plitzko

Max Planck Institute of Biochemistry

Hannes Rolbieski

Helmholtz Zentrum München

Helmut Fuchs

Helmholtz Zentrum München

Cooperative Institutions

Massachusetts Institute of Technology

Helmholtz Zentrum München

Technical University of Munich

Institute of Biological and Medical Imaging

Institute of Bioinformatics and Systems Biology

Utrecht University

IIT@MIT

McGovern Institute for Brain Research

Klinikum rechts der Isar

Heinrich Heine University Düsseldorf

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Bacterial encapsulins as orthogonal compartments for mammalian cell engineering

Nature Communications (2018)

Felix Sigmund Christoph Massner Philipp S. Erdmann Anja Stelzl Hannes Rolbieski

We genetically controlled compartmentalization in eukaryotic cells by heterologous expression of bacterial encapsulin shell and cargo proteins to engineer enclosed enzymatic reactions and size-constrained metal biomineralization. The shell protein (EncA) from Myxococcus xanthus auto-assembles into nanocompartments inside mammalian cells to which sets of native (EncB,C,D) and engineered cargo proteins self-target enabling localized bimolecular fluorescence and enzyme complementation. Encapsulation of the enzyme tyrosinase leads to the confinement of toxic melanin production for robust detection via multispectral optoacoustic tomography (MSOT). Co-expression of ferritin-like native cargo (EncB,C) results in efficient iron sequestration producing substantial contrast by magnetic resonance imaging (MRI) and allowing for magnetic cell sorting. The monodisperse, spherical, and iron-loading nanoshells are also excellent genetically encoded reporters for electron microscopy (EM). In general, eukaryotically expressed encapsulins enable cellular engineering of spatially confined multicomponent processes with versatile applications in multiscale molecular imaging, as well as intriguing implications for metabolic engineering and cellular therapy.

Magnetosome

Protein Engineering

Nanoshell

Synthetic Biology

Compartmentalization (fire protection)

Bioorthogonal Chemistry

10.1038/s41467-018-04227-3

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Citations (106)

Image-guided neural activity manipulation with a paramagnetic drug

Nature Communications (2020)

Sarah Bricault Ali Barandov P.K. Harvey Elizabeth DeTienne Aviad Hai

Abstract Targeted manipulations of neural activity are essential approaches in neuroscience and neurology, but monitoring such procedures in the living brain remains a significant challenge. Here we introduce a paramagnetic analog of the drug muscimol that enables targeted neural inactivation to be performed with feedback from magnetic resonance imaging. We validate pharmacological properties of the compound in vitro, and show that its distribution in vivo reliably predicts perturbations to brain activity.

Neural Activity

10.1038/s41467-019-13933-5

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Citations (14)

Bacterial encapsulins as orthogonal compartments for mammalian cell engineering

Nature (2018)

Felix Sigmund Christoph Massner Philipp S. Erdmann Anja Stelzl Hannes Rolbieski

Magnetosome

Protein Engineering

Nanoshell

Compartmentalization (fire protection)

Synthetic Biology

Bioorthogonal Chemistry

Magnetotactic Bacteria

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Peripheral contributions to resting state brain dynamics

Nature Communications (2024)

Sarah Bricault Miranda Dawson Ji‐Young Lee Mitul Desai Miriam Schwalm

The correlational structure of brain activity dynamics in the absence of stimuli or behavior is often taken to reveal intrinsic properties of neural function. To test the limits of this assumption, we analyzed peripheral contributions to resting state activity measured by fMRI in unanesthetized, chemically immobilized male rats that emulate human neuroimaging conditions. We find that perturbation of somatosensory input channels modifies correlation strengths that relate somatosensory areas both to one another and to higher-order brain regions, despite the absence of ostensible stimuli or movements. Resting state effects are mediated by the same peripheral and thalamic structures that relay responses to overt sensory stimuli. The impact of basal peripheral input is reduced in a rat model of autism, which displays both lower somatosensory functional connectivity and insensitivity to vibrissa inactivation. These results demonstrate the influence of extrinsic influences on resting state brain phenotypes in health and disease.

10.1038/s41467-024-55064-6

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