Menu

Close

In vivo glucose imaging in multiple model organisms with an engineered single-wavelength sensor

Jacob P. Keller, Jonathan S. Marvin, Haluk Lacin, William C. Lemon, Jamien Shea, Soomin Kim, Richard T. Lee, Minoru Koyama, Philipp J. Keller, Loren L. Looger

Preprint posted on March 08, 2019 https://www.biorxiv.org/content/10.1101/571422v1

How to visualize glucose concentrations in vivo: the Looger lab has engineered a new family of single-wavelength glucose sensors to unravel the biology of glucose in models such as tissue culture, Drosophila and zebrafish.

Selected by Stephan Daetwyler

Context

Glucose is one of the most important molecules of life. As a product of photosynthesis, it is a major organic compound that serves as an energy store, fuel for metabolic engines, and constituent of other molecules. Moreover, it is the major form of transport of carbohydrates from one cell to another in animals. Its importance is also highlighted by its tight regulation. In humans, an intricate system involving the pancreas, brain, liver, gut, adipose and muscle tissue acts together to regulate glucose levels via various hormones such as insulin and glucagon, neurotransmitters and cytokines [1]. Disturbances of this interplay lead to metabolic disorders such as type 2 diabetes mellitus [2]. Diabetes is a major cause of blindness, kidney failure, heart attacks, stroke and lower limb amputation affecting about 422 million people in 2014 [3]. Techniques to measure glucose concentrations in vivo are therefore of high clinical and scientific importance. While many glucose sensors have been established ranging from finger-prick to intravenous implantable devices [4], techniques relying on fluorescence are the most promising for basic research and the clinics [5].

Fluorescence microscopy offers very sensitive and non-invasive measurements. Most existing fluorescence-based glucose sensors, however, suffer from lack of specificity [6], targeting [7], or modest fluorescence responses [8]. This makes their application to imaging studies in living animals and plants with high spatial and temporal resolution difficult. Recently, a novel glucose sensor relying on circularly permuted yellow fluorescent protein combined with a bacterial periplasmic glucose / galactose-binding protein was introduced that can address the above issues [9]. However, its application has only been demonstrated in E. coli cells. In their new preprint, Keller et al. introduce a novel family of single-wavelength sensors and demonstrate their value for studies of glucose concentrations in tissue culture, Drosophila and zebrafish model systems.

Key findings

1. Engineering of a family of genetically encoded glucose sensors

In this new preprint, a family of genetically encoded glucose sensors with a high signal-to-noise ratio, fast kinetics and affinities from 1 mM to 10 mM has been introduced. At the heart of the new sensor, named iGlucoSnFR, is a circularly-permuted green fluorescent protein (cpGFP) that has been inserted into a glucose binding protein (GBP) from the thermophile bacterium T. thermophilus (Tt). Upon glucose binding of the GBP, the configuration of the sensor changes to yield higher fluorescence signal (Fig. 1). To complement the iGlucoSnFR for ratiometric measurements and/or cell typing, the glucose-insensitive red fluorescent protein mRuby2 has been fused to the C-terminus of iGlucoSnFR (iGlucoSnFR-mRuby2). Both variants have been established as cytosolic, secretable and membrane-bound versions. Using protein engineering, mutations in the linker and binding regions of the GBP have been introduced to optimize the affinity and fluorescence gain (ΔF/F) of the sensor. iGlucoSnFR shows high affinity to glucose (6.5 mM) compared to other sugars such as galactose (20 mM) and 2-deoxy-glucose (45 mM), and applicability at pH values ranging between pH 6.0-9.5.

Figure 1: Schematic of iGlucoSnFR sensor. Upon binding to glucose (orange), the glucose sensor iGlucoSnFR changes its configuration to yield higher fluorescent signal (dF/F = 2.32). The sensor consists of a circularly-permuted green fluorescent protein (cpGFP, green) inserted into the glucose-binding protein (GBP, light and dark blue) from the thermophile bacterium T. thermophilus.

 

2. Demonstration of the glucose sensor in various applications

The novel glucose sensors have been applied to study neuron/glia co-cultures, larval Drosophila central nervous system explants, and zebrafish larvae. The experiments show that the new sensor can be easily targeted to specific populations of cells to visualize changes in glucose levels.

Importance

Applications of this novel glucose sensor to various biological questions are imminent. With this sensor in hand, spatiotemporal dynamics of glucose trafficking, maintenance and regulation on scales ranging from whole organisms to intracellular levels can be discerned. The opportunity to express this sensor in specific cell populations and specific intracellular components will open new ways to address long-standing questions in fields as diverse as development, behavioral science, neuroscience, metabolism and biology of disease such as cancer and diabetes.

Future directions and questions

  • Have the authors acquired high-resolution images of single cells with subcellular resolution? If yes, have the authors found interesting subcellular localization patterns of glucose? Along these lines, the authors also report the establishment of membrane-bound and secreted versions of their glucose sensors. How do they compare to the cytosolic sensor discussed in the preprint?
  • Can the authors elaborate why circularly-permuted variants of fluorescent proteins such as GFP are particularly suited for the construction of sensors?
  • Have the authors thought of or already performed long-term measurements of how glucose levels change during development in general, and specifically in different regions? A particularly exciting question would be to understand how onset of blood perfusion in a tissue changes local glucose levels.
  • Glucose monitoring in patients with diabetes is still often relying on a finger-prick glucometer. Do the authors of the study envision whether their novel sensor could help diabetes patients by providing novel tools to accurately measure glucose levels?

References

[1]       Röder PV, Wu B, Liu Y, Han W. Pancreatic regulation of glucose homeostasis. Experimental & Molecular Medicine 2016;48:e219–e219. doi:10.1038/emm.2016.6.

[2]       DeFronzo RA, Ferrannini E, Groop L, Henry RR, Herman WH, Holst JJ, et al. Type 2 diabetes mellitus. Nature Reviews Disease Primers 2015;1:15019.

[3]       World Health Organization. Diabetes Fact Sheet n.d. https://www.who.int/news-room/fact-sheets/detail/diabetes (accessed March 28, 2019).

[4]       Oliver NS, Toumazou C, Cass AEG, Johnston DG. Glucose sensors: a review of current and emerging technology. Diabetic Medicine 2009;26:197–210. doi:10.1111/j.1464-5491.2008.02642.x.

[5]       Wang H-C, Lee A-R. Recent developments in blood glucose sensors. Journal of Food and Drug Analysis 2015;23:191–200. doi:10.1016/j.jfda.2014.12.001.

[6]       Mandal DK, Bhattacharyya L, Koenig SH, Brown RD, Oscarson S, Brewer CF. Studies of the Binding Specificity of Concanavalin A. Nature of the Extended Binding Site for Asparagine-Linked Carbohydrates. Biochemistry 1994;33:1157–62. doi:10.1021/bi00171a015.

[7]       Ge X, Tolosa L, Rao G. Dual-Labeled Glucose Binding Protein for Ratiometric Measurements of Glucose. Anal Chem 2004;76:1403–10. doi:10.1021/ac035063p.

[8]       Deuschle K, Okumoto S, Fehr M, Looger LL, Kozhukh L, Frommer WB. Construction and optimization of a family of genetically encoded metabolite sensors by semirational protein engineering. Protein Sci 2005;14:2304–14. doi:10.1110/ps.051508105.

[9]       Hu H, Wei Y, Wang D, Su N, Chen X, Zhao Y, et al. Glucose monitoring in living cells with single fluorescent protein-based sensors. RSC Adv 2018;8:2485–9. doi:10.1039/C7RA11347A.

 

Tags: drosophila, glucose, sensor, zebrafish

Posted on: 5th April 2019

Read preprint (No Ratings Yet)




  • Author's response

    Jacob Keller and Loren Looger shared

    • Have the authors acquired high-resolution images of single cells with subcellular resolution? If yes, have the authors found interesting subcellular localization patterns of glucose? Along these lines, the authors also report the establishment of membrane-bound and secreted versions of their glucose sensors. How do they compare to the cytosolic sensor discussed in the preprint?

    We have looked only briefly at subcellular glucose, since we wanted to focus first on what other researchers might find most useful, but we agree that subcellular glucose imaging/measurements are fascinating. We have done a bit, though: in a previous paper {PMID: 27716484}, we expressed iGlucoSnFR in the lumen of the endoplasmic reticulum (ER), and showed that ER membranes are permeable to glucose, likely via ER-localized glucose transporters. There is much left to be learned about sub-cellular glucose trafficking, e.g. into the ER, mitochondria and axon terminals.

    To really address subcellular glucose trafficking, something like a lattice light-sheet microscope would be best, since high-resolution, volumetric time-lapse imaging would really bring out the most from the experiments.

    Regarding the differentially localized versions, we did not explore their use extensively, but did confirm that the extracellular version is successfully targeted to the membrane in cultured cells and in larval zebrafish mosaics, and also confirmed that the secreted version appears in the media of cultured cells. Admittedly, more work is definitely warranted on those two versions. We think that the secreted version in particular might work well in the CNS as a sensor of extracellular CSF glucose: with exchangeability and a higher amount of sensor-volume compared to the membrane-localized version, photobleaching would likely be significantly reduced, and the entire CNS should be homogeneously filled with sensor.

    • Can the authors elaborate why circularly-permuted variants of fluorescent proteins such as GFP are particularly suited for the construction of sensors?

    When the protein is circularly permuted in this fashion, the new termini end up immediately adjacent to the chromophore. This allows conformational changes in the PBPs to perturb the chromophore’s local environment, thus modulating its fluorescence properties. This trick has now been used to make a large number of sensors.

    • Have the authors thought of or already performed long-term measurements of how glucose levels change during development in general, and specifically in different regions? A particularly exciting question would be to understand how onset of blood perfusion in a tissue changes local glucose levels.

    Regarding long-term measurements, one has to appreciate that sensor expression levels can change over time, introducing confounding signals. This can to some extent be countered by performing ratiometry with the mRuby2-tagged version, but it is significantly harder, generally, to keep experimental subjects stable over long periods of time. With sufficient care, however, it should be possible.

    The question of blood perfusion, we agree heartily, would be an interesting one, and welcome you or others to try it. The transgenic flies have been deposited at Bloomington. The DNA constructs and AAV viruses have been sent to Addgene. The transgenic fish are freely available from the HHMI Janelia Research Campus.

    • Glucose monitoring in patients with diabetes is still often relying on a finger-prick glucometer. Do the authors of the study envision whether their novel sensor could help diabetes patients by providing novel tools to accurately measure glucose levels?

    Yes, we have considered this, and think that with the array of affinities that we have and a bit of standardization, a very accurate, precise, and rapid assay could be developed. We should point out that there has been a great deal of previous work in diabetic glucose monitoring, and this is tricky to get right. One interesting avenue is that since the biosensors are totally genetically encoded, patients’ own cells or tissues can be harnessed to measure glucose concentrations in real time. This could facilitate studies of patient-specific differences in glucose metabolism and trafficking and improve our understanding of metabolic disorders, potentially allowing diabetes management strategies to be tailored for specific patient populations.

    Have your say

    Your email address will not be published. Required fields are marked *

    This site uses Akismet to reduce spam. Learn how your comment data is processed.

    Sign up to customise the site to your preferences and to receive alerts

    Register here

    Also in the animal behavior and cognition category:

    Active behaviour during early development shapes glucocorticoid reactivity

    Luis A. Castillo-Ramírez, Soojin Ryu, Rodrigo J. De Marco



    Selected by Kathleen Gilmour

    Blue light induces neuronal-activity-regulated gene expression in the absence of optogenetic proteins

    Kelsey M. Tyssowski, Jesse M. Gray



    Selected by Zheng-Shan Chong

    Establishment of the mayfly Cloeon dipterum as a new model system to investigate insect evolution

    Isabel Almudi, Carlos Martin-Blanco, Isabel Maria Garcia-Fernandez, et al.



    Selected by Ivan Candido-Ferreira

    1

    Regulation of modulatory cell activity across olfactory structures in Drosophila melanogaster

    Xiaonan Zhang, Kaylynn Coates, Andrew Dacks, et al.



    Selected by Rudra Nayan Das

    1

    Elaborate pupils in skates may help camouflage the eye

    Sean Youn, Corey Okinaka, Lydia Mathger



    Selected by Carola Yovanovich

    Distributed correlates of visually-guided behavior across the mouse brain

    Nicholas Steinmetz, Peter Zatka-Haas, Matteo Carandini, et al.



    Selected by Craig Bertram

    Psychiatric risk gene NT5C2 regulates protein translation in human neural progenitor cells

    Rodrigo R.R. Duarte, Nathaniel D. Bachtel, Marie-Caroline Cotel, et al.



    Selected by Joanna Cross

    1

    Predation risk and resource abundance mediate foraging behaviour and intraspecific resource partitioning among consumers in dominance hierarchies

    Sean Naman, Rui Ueda, Takuya Sato



    Selected by Rasmus Ern

    Antlions are sensitive to subnanometer amplitude vibrations carried by sand substrates

    Vanessa Martinez, Elise Nowbahari, David Sillam-Dussès, et al.



    Selected by James Foster

    Optogenetic manipulation of medullary neurons in the locust optic lobe

    Hongxia Wang, Richard B. Dewell, Markus U. Ehrengruber, et al.



    Selected by Ana Patricia Ramos

    Phenotypic landscape of schizophrenia-associated genes defines candidates and their shared functions

    Summer B. Thyme, Lindsey M. Pieper, Eric H. Li, et al.



    Selected by Daniel Grimes

    Using a robotic fish to investigate individual differences in social responsiveness in the guppy

    David Bierbach, Tim Landgraf, Pawel Romanczuk, et al.



    Selected by Rasmus Ern

    Molecular dynamics simulations disclose early stages of the photo-activation of cryptochrome 4

    Daniel R. Kattnig, Claus Nielsen, Ilia A. Solov'yov



    Selected by Miriam Liedvogel

    1

    Small differences in learning speed for different food qualities can drive efficient collective foraging in ant colonies

    Felix B Oberhauser, Alexandra Koch, Tomer J Czaczkes



    Selected by James Foster

    Individual- and population-level drivers of consistent foraging success across environments

    Lysanne Snijders, Ralf HJM Kurvers, Stefan Krause, et al.



    Selected by Rasmus Ern

    From Armament to Ornament: Performance Trade-Offs in the Sexual Weaponry of Neotropical Electric Fishes

    Kory M. Evans, Maxwell J. Bernt, Matthew A. Kolmann, et al.



    Selected by Cassandra Donatelli

    Also in the bioengineering category:

    A Bile Duct-on-a-Chip with Organ-Level Functions

    Yu Du, Gauri Khandekar, Jessica Llewellyn, et al.



    Selected by Zhang-He Goh

    In vivo glucose imaging in multiple model organisms with an engineered single-wavelength sensor

    Jacob P. Keller, Jonathan S. Marvin, Haluk Lacin, et al.



    Selected by Stephan Daetwyler

    1

    Engineered Enzymes that Retain and Regenerate their Cofactors Enable Continuous-Flow Biocatalysis

    Carol J. Hartley, Charlotte C. Williams, Judith A. Scoble, et al.



    Selected by Zhang-He Goh

    1

    Multi-immersion open-top light-sheet microscope for high-throughput imaging of cleared tissues

    Adam K. Glaser, Nicholas P. Reder, Ye Chen, et al.



    Selected by Tim Fessenden

    1

    Optical determination of absolute membrane potential

    Julia R. Lazzari-Dean, Anneliese M.M. Gest, Evan Miller



    Selected by James Marchant

    Conditional Guide RNAs: Programmable Conditional Regulation of CRISPR/Cas Function in Bacteria via Dynamic RNA Nanotechnology

    Mikhail H. Hanewich-Hollatz, Zhewei Chen, Jining Huang, et al.



    Selected by Pavithran Ravindran

    1

    A DNA-based voltmeter for organelles

    Anand Saminathan, John Devany, Kavya S Pillai, et al.



    Selected by Robert Mahen

    1

    Defining the design requirements for an assistive powered hand exoskeleton

    Quinn A Boser, Michael R Dawson, Jonathon S Schofield, et al.



    Selected by Joanna Cross

    Imaging mechanical properties of sub-micron ECM in live zebrafish using Brillouin microscopy

    Carlo Bevilacqua, Héctor Sánchez Iranzo, Dmitry Richter, et al.



    Selected by Stephan Daetwyler

    1

    DNA microscopy: Optics-free spatio-genetic imaging by a stand-alone chemical reaction

    Joshua A. Weinstein, Aviv Regev, Feng Zhang



    Selected by Theo Sanderson

    2

    Polyacrylamide Bead Sensors for in vivo Quantification of Cell-Scale Stress in Zebrafish Development

    Nicole Traeber, Klemens Uhlmann, Salvatore Girardo, et al.



    Selected by Jacky G. Goetz

    SABER enables highly multiplexed and amplified detection of DNA and RNA in cells and tissues

    Jocelyn Y. Kishi, Brian J. Beliveau, Sylvain W. Lapan, et al.



    Selected by Yen-Chung Chen

    Live-cell imaging of marked chromosome regions reveals dynamics of mitotic chromosome resolution and compaction

    John K Eykelenboom, Marek Gierlinski, Zuojun Yue, et al.

    AND

    Quantitative imaging of chromatin decompaction in living cells

    Elisa Dultz, Roberta Mancini, Guido Polles, et al.



    Selected by Carmen Adriaens, Gautam Dey

    HIF1-alpha expressing cells induce a hypoxic-like response in neighbouring cancer cells

    Hannah Harrison, Henry J Pegg, Jamie Thompson, et al.



    Selected by Anh Hoang Le

    Zebrafish as a model to investigate the effects of exercise in cancer

    Alexandra Yin, Nathaniel R. Campbell, Lee W. Jones, et al.



    Selected by Jacky G. Goetz

    A 3D model of human skeletal muscle innervated with stem cell-derived motor neurons enables epsilon-subunit targeted myasthenic syndrome studies

    Mohsen Afshar Bakooshli, Ethan S Lippmann, Ben Mulcahy, et al.



    Selected by Chris Demers

    Also in the cell biology category:

    The autophagic membrane tether ATG2A transfers lipids between membranes

    Shintaro Maeda, Chinatsu Otomo, Takanori Otomo



    Selected by Sandra Malmgren Hill

    LTK is an ER-resident receptor tyrosine kinase that regulates secretion

    Federica G. Centonze, Veronika Reiterer, Karsten Nalbach, et al.



    Selected by Nicola Stevenson

    1

    Distinct RhoGEFs activate apical and junctional actomyosin contractility under control of G proteins during epithelial morphogenesis

    Alain Garcia De Las Bayonas, Jean-Marc Philippe, Annemarie C. Lellouch, et al.



    Selected by Ivana Viktorinová

    1

    In vivo glucose imaging in multiple model organisms with an engineered single-wavelength sensor

    Jacob P. Keller, Jonathan S. Marvin, Haluk Lacin, et al.



    Selected by Stephan Daetwyler

    1

    The spindle assembly checkpoint functions during early development in non-chordate embryos

    Janet Chenevert, Marianne Roca, Lydia Besnardeau, et al.



    Selected by Maiko Kitaoka

    Blue light induces neuronal-activity-regulated gene expression in the absence of optogenetic proteins

    Kelsey M. Tyssowski, Jesse M. Gray



    Selected by Zheng-Shan Chong

    Mutations in the Insulator Protein Suppressor of Hairy Wing Induce Genome Instability

    Shih-Jui Hsu, Emily C. Stow, James R. Simmons, et al.



    Selected by Maiko Kitaoka

    1

    Multi-immersion open-top light-sheet microscope for high-throughput imaging of cleared tissues

    Adam K. Glaser, Nicholas P. Reder, Ye Chen, et al.



    Selected by Tim Fessenden

    1

    ATAT1-enriched vesicles promote microtubule acetylation via axonal transport

    Aviel Even, Giovanni Morelli, Chiara Scaramuzzino, et al.



    Selected by Stephen Royle

    1

    HIV-1 Gag specifically restricts PI(4,5)P2 and cholesterol mobility in living cells creating a nanodomain platform for virus assembly

    C. Favard, J. Chojnacki, P. Merida, et al.



    Selected by Amberley Stephens

    Hepatocyte-specific deletion of Pparα promotes NASH in the context of obesity

    Marion Regnier, Arnaud Polizzi, Sarra Smati, et al.



    Selected by Pablo Ranea Robles

    Mitochondrial biogenesis is transcriptionally repressed in lysosomal lipid storage diseases

    King Faisal Yambire, Lorena Fernandez-Mosquera, Robert Steinfeld, et al.



    Selected by Sandra Franco Iborra

    1

    Thyroid hormone regulates distinct paths to maturation in pigment cell lineages

    Lauren Saunders, Abhishek Mishra, Andrew J Aman, et al.



    Selected by Hannah Brunsdon

    1

    Kinesin-6 Klp9 plays motor-dependent and -independent roles in collaboration with Kinesin-5 Cut7 and the microtubule crosslinker Ase1 in fission yeast

    Masashi Yukawa, Masaki Okazaki, Yasuhiro Teratani, et al.



    Selected by I. Bouhlel

    A pair of E3 ubiquitin ligases compete to regulate filopodial dynamics and axon guidance

    Nicholas P Boyer, Laura E McCormick, Fabio L Urbina, et al.



    Selected by Angika Basant

    1

    SorCS1-mediated Sorting of Neurexin in Dendrites Maintains Presynaptic Function

    Luis Filipe Ribeiro, Ben Verpoort, Julie Nys, et al.



    Selected by Carmen Adriaens

    1

    Also in the developmental biology category:

    The visual system of the genetically tractable crustacean Parhyale hawaiensis: diversification of eyes and visual circuits associated with low-resolution vision

    Ana Patricia Ramos, Ola Gustafsson, Nicolas Labert, et al.



    Selected by Alexa Sadier

    Distinct RhoGEFs activate apical and junctional actomyosin contractility under control of G proteins during epithelial morphogenesis

    Alain Garcia De Las Bayonas, Jean-Marc Philippe, Annemarie C. Lellouch, et al.



    Selected by Ivana Viktorinová

    1

    The Hunchback temporal transcription factor determines motor neuron axon and dendrite targeting in Drosophila

    Austin Q Seroka, Chris Q Doe



    Selected by Abagael Lasseigne

    1

    Preformed Chromatin Topology Assists Transcriptional Robustness of Shh during Limb Development

    Christina Paliou, Philine Guckelberger, Robert Schöpflin, et al.



    Selected by Rafael Galupa

    1

    Molecular Logic of Spinocerebellar Tract Neuron Diversity and Connectivity

    Myungin Baek, Vilas Menon, Thomas Jessell, et al.



    Selected by Yen-Chung Chen

    In vivo glucose imaging in multiple model organisms with an engineered single-wavelength sensor

    Jacob P. Keller, Jonathan S. Marvin, Haluk Lacin, et al.



    Selected by Stephan Daetwyler

    1

    Active behaviour during early development shapes glucocorticoid reactivity

    Luis A. Castillo-Ramírez, Soojin Ryu, Rodrigo J. De Marco



    Selected by Kathleen Gilmour

    A unicellular relative of animals generates an epithelium-like cell layer by actomyosin-dependent cellularization

    Omaya Dudin, Andrej Ondracka, Xavier Grau-Bové, et al.



    Selected by Paul Gerald L. Sanchez and Stefano Vianello

    1

    Members of the Arabidopsis auxin receptor gene family are essential early in embryogenesis and have broadly overlapping functions

    Michael J Prigge, Nikita Kadakia, Kathleen Greenham, et al.



    Selected by Chandra Shekhar Misra

    1

    The spindle assembly checkpoint functions during early development in non-chordate embryos

    Janet Chenevert, Marianne Roca, Lydia Besnardeau, et al.



    Selected by Maiko Kitaoka

    Over-activation of BMP signaling in neural crest cells precipitates heart outflow tract septation

    Jean Francois Darrigrand, Mariana Valente, Pauline Martinez, et al.



    Selected by Giulia Boezio

    Mutations in the Insulator Protein Suppressor of Hairy Wing Induce Genome Instability

    Shih-Jui Hsu, Emily C. Stow, James R. Simmons, et al.



    Selected by Maiko Kitaoka

    1

    Multi-immersion open-top light-sheet microscope for high-throughput imaging of cleared tissues

    Adam K. Glaser, Nicholas P. Reder, Ye Chen, et al.



    Selected by Tim Fessenden

    1

    Dynamic Erasure of Random X-Chromosome Inactivation during iPSC Reprogramming

    Adrian Janiszewski, Irene Talon, Juan Song, et al.



    Selected by Sergio Menchero

    MicroRNA-mediated control of developmental lymphangiogenesis

    Hyun Min Jung, Ciara Hu, Alexandra M Fister, et al.



    Selected by Rudra Nayan Das

    Endogenous CRISPR arrays for scalable whole organism lineage tracing

    James Cotterell, James Sharpe



    Selected by Irepan Salvador-Martinez

    Also in the neuroscience category:

    The Hunchback temporal transcription factor determines motor neuron axon and dendrite targeting in Drosophila

    Austin Q Seroka, Chris Q Doe



    Selected by Abagael Lasseigne

    1

    Molecular Logic of Spinocerebellar Tract Neuron Diversity and Connectivity

    Myungin Baek, Vilas Menon, Thomas Jessell, et al.



    Selected by Yen-Chung Chen

    In vivo glucose imaging in multiple model organisms with an engineered single-wavelength sensor

    Jacob P. Keller, Jonathan S. Marvin, Haluk Lacin, et al.



    Selected by Stephan Daetwyler

    1

    Blue light induces neuronal-activity-regulated gene expression in the absence of optogenetic proteins

    Kelsey M. Tyssowski, Jesse M. Gray



    Selected by Zheng-Shan Chong

    A pair of E3 ubiquitin ligases compete to regulate filopodial dynamics and axon guidance

    Nicholas P Boyer, Laura E McCormick, Fabio L Urbina, et al.



    Selected by Angika Basant

    1

    Prospective, brain-wide labeling of neuronal subclasses with enhancer-driven AAVs

    Lucas T Graybuck, Adriana Sedeño-Cortés, Thuc Nghi Nguyen, et al.



    Selected by Jesus Victorino

    SorCS1-mediated Sorting of Neurexin in Dendrites Maintains Presynaptic Function

    Luis Filipe Ribeiro, Ben Verpoort, Julie Nys, et al.



    Selected by Carmen Adriaens

    1

    Multilevel regulation of the glass locus during Drosophila eye development

    Cornelia Fritsch, F. Javier Bernardo-Garcia, Tim Humberg, et al.



    Selected by Gabriel Aughey

    1

    Regulation of modulatory cell activity across olfactory structures in Drosophila melanogaster

    Xiaonan Zhang, Kaylynn Coates, Andrew Dacks, et al.



    Selected by Rudra Nayan Das

    1

    On-site ribosome remodeling by locally synthesized ribosomal proteins in axons

    Toshiaki Shigeoka, Max Koppers, Hovy Ho-Wai Wong, et al.



    Selected by Srivats Venkataramanan

    Single cell RNA-Seq reveals distinct stem cell populations that drive sensory hair cell regeneration in response to loss of Fgf and Notch signaling

    Mark E. Lush, Daniel C. Diaz, Nina Koenecke, et al.

    AND

    Distinct progenitor populations mediate regeneration in the zebrafish lateral line.

    Eric D Thomas, David Raible



    Selected by Rudra Nayan Das

    2

    A schizophrenia risk gene, NRGN, bidirectionally modulates synaptic plasticity via regulating the neuronal phosphoproteome

    Hongik Hwang, Matthew J Szucs, Lei J Ding, et al.



    Selected by Laura McCormick

    Actomyosin-II facilitates long-range retrograde transport of large cargoes by controlling axonal radial contractility

    Tong Wang, Wei Li, Sally Martin, et al.



    Selected by Ivana Viktorinová

    Unlimited genetic switches for cell-type specific manipulation

    Jorge Garcia-Marques, Ching-Po Yang, Isabel Espinosa-Medina, et al.



    Selected by Rafael Almeida

    1

    Defining the design requirements for an assistive powered hand exoskeleton

    Quinn A Boser, Michael R Dawson, Jonathon S Schofield, et al.



    Selected by Joanna Cross

    Strong preference for autaptic self-connectivity of neocortical PV interneurons entrains them to γ-oscillations

    Charlotte Deleuze, Gary S Bhumbra, Antonio Pazienti, et al.



    Selected by Mahesh Karnani

    Also in the physiology category:

    In vivo glucose imaging in multiple model organisms with an engineered single-wavelength sensor

    Jacob P. Keller, Jonathan S. Marvin, Haluk Lacin, et al.



    Selected by Stephan Daetwyler

    1

    Active behaviour during early development shapes glucocorticoid reactivity

    Luis A. Castillo-Ramírez, Soojin Ryu, Rodrigo J. De Marco



    Selected by Kathleen Gilmour

    Optical determination of absolute membrane potential

    Julia R. Lazzari-Dean, Anneliese M.M. Gest, Evan Miller



    Selected by James Marchant

    Hepatocyte-specific deletion of Pparα promotes NASH in the context of obesity

    Marion Regnier, Arnaud Polizzi, Sarra Smati, et al.



    Selected by Pablo Ranea Robles

    A DNA-based voltmeter for organelles

    Anand Saminathan, John Devany, Kavya S Pillai, et al.



    Selected by Robert Mahen

    1

    Quantification of microenvironmental metabolites in murine cancer models reveals determinants of tumor nutrient availability

    Mark R Sullivan, Laura V Danai, Caroline A Lewis, et al.



    Selected by Maria Rafaeva

    1

    Regulation of modulatory cell activity across olfactory structures in Drosophila melanogaster

    Xiaonan Zhang, Kaylynn Coates, Andrew Dacks, et al.



    Selected by Rudra Nayan Das

    1

    EHD2-mediated restriction of caveolar dynamics regulates cellular lipid uptake

    Claudia Matthaeus, Ines Lahmann, Severine Kunz, et al.



    Selected by Andreas Müller

    1

    Super-resolution Molecular Map of Basal Foot Reveals Novel Cilium in Airway Multiciliated Cells

    Quynh Nguyen, Zhen Liu, Rashmi Nanjundappa, et al.



    Selected by Robert Mahen

    Defining the design requirements for an assistive powered hand exoskeleton

    Quinn A Boser, Michael R Dawson, Jonathon S Schofield, et al.



    Selected by Joanna Cross

    Reduced mitochondrial lipid oxidation leads to fat accumulation in myosteatosis

    Jonathan P Gumucio, Austin H Qasawa, Patrick J Ferrara, et al.



    Selected by Pablo Ranea Robles

    The Toll pathway inhibits tissue growth and regulates cell fitness in an infection-dependent manner

    Federico Germani, Daniel Hain, Denise Sternlicht, et al.



    Selected by Rohan Khadilkar

    Optogenetic manipulation of medullary neurons in the locust optic lobe

    Hongxia Wang, Richard B. Dewell, Markus U. Ehrengruber, et al.



    Selected by Ana Patricia Ramos

    Targeting light-gated chloride channels to neuronal somatodendritic domain reduces their excitatory effect in the axon

    Jessica Messier, Hongmei Chen, Zhao-Lin Cai, et al.

    AND

    High-efficiency optogenetic silencing with soma-targeted anion-conducting channelrhodopsins

    Mathias Mahn, Lihi Gibor, Katayun Cohen-Kashi Malina, et al.



    Selected by Mahesh Karnani

    2

    Rearing temperature and fatty acid supplementation jointly affect membrane fluidity and heat tolerance in Daphnia

    Dominik Martin-Creuzburg, Bret L. Coggins, Dieter Ebert, et al.



    Selected by Alexander Little

    Long-term live imaging of the Drosophila adult midgut reveals real-time dynamics of cell division, differentiation, and loss

    Judy Martin, Erin Nicole Sanders, Paola Moreno-Roman, et al.



    Selected by Natalie Dye
    Close