Filter
Associated Lab
- Aguilera Castrejon Lab (1) Apply Aguilera Castrejon Lab filter
- Ahrens Lab (46) Apply Ahrens Lab filter
- Aso Lab (39) Apply Aso Lab filter
- Baker Lab (19) Apply Baker Lab filter
- Betzig Lab (99) Apply Betzig Lab filter
- Beyene Lab (5) Apply Beyene Lab filter
- Bock Lab (14) Apply Bock Lab filter
- Branson Lab (45) Apply Branson Lab filter
- Card Lab (34) Apply Card Lab filter
- Cardona Lab (44) Apply Cardona Lab filter
- Chklovskii Lab (10) Apply Chklovskii Lab filter
- Clapham Lab (12) Apply Clapham Lab filter
- Cui Lab (19) Apply Cui Lab filter
- Darshan Lab (8) Apply Darshan Lab filter
- Dickson Lab (32) Apply Dickson Lab filter
- Druckmann Lab (21) Apply Druckmann Lab filter
- Dudman Lab (34) Apply Dudman Lab filter
- Eddy/Rivas Lab (30) Apply Eddy/Rivas Lab filter
- Egnor Lab (4) Apply Egnor Lab filter
- Espinosa Medina Lab (12) Apply Espinosa Medina Lab filter
- Feliciano Lab (6) Apply Feliciano Lab filter
- Fetter Lab (31) Apply Fetter Lab filter
- Fitzgerald Lab (15) Apply Fitzgerald Lab filter
- Freeman Lab (15) Apply Freeman Lab filter
- Funke Lab (35) Apply Funke Lab filter
- Gonen Lab (59) Apply Gonen Lab filter
- Grigorieff Lab (34) Apply Grigorieff Lab filter
- Harris Lab (48) Apply Harris Lab filter
- Heberlein Lab (13) Apply Heberlein Lab filter
- Hermundstad Lab (18) Apply Hermundstad Lab filter
- Hess Lab (69) Apply Hess Lab filter
- Ilanges Lab (1) Apply Ilanges Lab filter
- Jayaraman Lab (40) Apply Jayaraman Lab filter
- Ji Lab (33) Apply Ji Lab filter
- Johnson Lab (1) Apply Johnson Lab filter
- Karpova Lab (13) Apply Karpova Lab filter
- Keleman Lab (8) Apply Keleman Lab filter
- Keller Lab (60) Apply Keller Lab filter
- Koay Lab (1) Apply Koay Lab filter
- Lavis Lab (126) Apply Lavis Lab filter
- Lee (Albert) Lab (29) Apply Lee (Albert) Lab filter
- Leonardo Lab (19) Apply Leonardo Lab filter
- Li Lab (3) Apply Li Lab filter
- Lippincott-Schwartz Lab (89) Apply Lippincott-Schwartz Lab filter
- Liu (Zhe) Lab (56) Apply Liu (Zhe) Lab filter
- Looger Lab (136) Apply Looger Lab filter
- Magee Lab (31) Apply Magee Lab filter
- Menon Lab (12) Apply Menon Lab filter
- Murphy Lab (6) Apply Murphy Lab filter
- O'Shea Lab (5) Apply O'Shea Lab filter
- Otopalik Lab (1) Apply Otopalik Lab filter
- Pachitariu Lab (30) Apply Pachitariu Lab filter
- Pastalkova Lab (5) Apply Pastalkova Lab filter
- Pavlopoulos Lab (7) Apply Pavlopoulos Lab filter
- Pedram Lab (3) Apply Pedram Lab filter
- Podgorski Lab (16) Apply Podgorski Lab filter
- Reiser Lab (43) Apply Reiser Lab filter
- Riddiford Lab (20) Apply Riddiford Lab filter
- Romani Lab (29) Apply Romani Lab filter
- Rubin Lab (101) Apply Rubin Lab filter
- Saalfeld Lab (44) Apply Saalfeld Lab filter
- Satou Lab (1) Apply Satou Lab filter
- Scheffer Lab (36) Apply Scheffer Lab filter
- Schreiter Lab (45) Apply Schreiter Lab filter
- Shroff Lab (24) Apply Shroff Lab filter
- Simpson Lab (18) Apply Simpson Lab filter
- Singer Lab (37) Apply Singer Lab filter
- Spruston Lab (55) Apply Spruston Lab filter
- Stern Lab (69) Apply Stern Lab filter
- Sternson Lab (47) Apply Sternson Lab filter
- Stringer Lab (26) Apply Stringer Lab filter
- Svoboda Lab (131) Apply Svoboda Lab filter
- Tebo Lab (7) Apply Tebo Lab filter
- Tervo Lab (9) Apply Tervo Lab filter
- Tillberg Lab (14) Apply Tillberg Lab filter
- Tjian Lab (17) Apply Tjian Lab filter
- Truman Lab (58) Apply Truman Lab filter
- Turaga Lab (34) Apply Turaga Lab filter
- Turner Lab (24) Apply Turner Lab filter
- Vale Lab (6) Apply Vale Lab filter
- Voigts Lab (2) Apply Voigts Lab filter
- Wang (Meng) Lab (10) Apply Wang (Meng) Lab filter
- Wang (Shaohe) Lab (5) Apply Wang (Shaohe) Lab filter
- Wu Lab (8) Apply Wu Lab filter
- Zlatic Lab (26) Apply Zlatic Lab filter
- Zuker Lab (5) Apply Zuker Lab filter
Associated Project Team
- CellMap (6) Apply CellMap filter
- COSEM (3) Apply COSEM filter
- Fly Descending Interneuron (10) Apply Fly Descending Interneuron filter
- Fly Functional Connectome (14) Apply Fly Functional Connectome filter
- Fly Olympiad (5) Apply Fly Olympiad filter
- FlyEM (51) Apply FlyEM filter
- FlyLight (46) Apply FlyLight filter
- GENIE (40) Apply GENIE filter
- Integrative Imaging (1) Apply Integrative Imaging filter
- Larval Olympiad (2) Apply Larval Olympiad filter
- MouseLight (16) Apply MouseLight filter
- NeuroSeq (1) Apply NeuroSeq filter
- ThalamoSeq (1) Apply ThalamoSeq filter
- Tool Translation Team (T3) (24) Apply Tool Translation Team (T3) filter
- Transcription Imaging (45) Apply Transcription Imaging filter
Associated Support Team
- Project Pipeline Support (1) Apply Project Pipeline Support filter
- Anatomy and Histology (18) Apply Anatomy and Histology filter
- Cryo-Electron Microscopy (33) Apply Cryo-Electron Microscopy filter
- Electron Microscopy (13) Apply Electron Microscopy filter
- Gene Targeting and Transgenics (11) Apply Gene Targeting and Transgenics filter
- Integrative Imaging (13) Apply Integrative Imaging filter
- Invertebrate Shared Resource (39) Apply Invertebrate Shared Resource filter
- Janelia Experimental Technology (35) Apply Janelia Experimental Technology filter
- Management Team (1) Apply Management Team filter
- Molecular Genomics (15) Apply Molecular Genomics filter
- Primary & iPS Cell Culture (13) Apply Primary & iPS Cell Culture filter
- Project Technical Resources (37) Apply Project Technical Resources filter
- Quantitative Genomics (19) Apply Quantitative Genomics filter
- Scientific Computing Software (63) Apply Scientific Computing Software filter
- Scientific Computing Systems (6) Apply Scientific Computing Systems filter
- Viral Tools (14) Apply Viral Tools filter
- Vivarium (6) Apply Vivarium filter
Publication Date
- 2024 (170) Apply 2024 filter
- 2023 (170) Apply 2023 filter
- 2022 (166) Apply 2022 filter
- 2021 (174) Apply 2021 filter
- 2020 (177) Apply 2020 filter
- 2019 (177) Apply 2019 filter
- 2018 (206) Apply 2018 filter
- 2017 (186) Apply 2017 filter
- 2016 (191) Apply 2016 filter
- 2015 (195) Apply 2015 filter
- 2014 (190) Apply 2014 filter
- 2013 (136) Apply 2013 filter
- 2012 (112) Apply 2012 filter
- 2011 (98) Apply 2011 filter
- 2010 (61) Apply 2010 filter
- 2009 (56) Apply 2009 filter
- 2008 (40) Apply 2008 filter
- 2007 (21) Apply 2007 filter
- 2006 (3) Apply 2006 filter
2529 Janelia Publications
Showing 1491-1500 of 2529 resultsCoordinated motor behaviors depend on feedback communication between peripheral sensory systems and central circuits in the brain and spinal cord. Relay of muscle and tendon-derived sensory information to the CNS is facilitated by functionally and anatomically diverse groups of spinocerebellar tract neurons (SCTNs), but the molecular logic by which SCTN diversity and connectivity is achieved is poorly understood. We used single cell RNA sequencing and genetic manipulations to define the mechanisms governing the molecular profile and organization of SCTN subtypes. We found that SCTNs relaying proprioceptive sensory information from limb and axial muscles are generated through segmentally-restricted actions of specific Hox genes. Loss of Hox function disrupts SCTN subtype-specific transcriptional programs, leading to defects in the connections between proprioceptive sensory neurons, SCTNs, and the cerebellum. These results indicate that Hox-dependent genetic programs play essential roles in the assembly of the neural circuits required for proprioception.
Focal adhesions (FAs) link the extracellular matrix to the actin cytoskeleton to mediate cell adhesion, migration, mechanosensing and signalling. FAs have conserved nanoscale protein organization, suggesting that the position of proteins within FAs regulates their activity and function. Vinculin binds different FA proteins to mediate distinct cellular functions, but how vinculin's interactions are spatiotemporally organized within FAs is unknown. Using interferometric photoactivation localization super-resolution microscopy to assay vinculin nanoscale localization and a FRET biosensor to assay vinculin conformation, we found that upward repositioning within the FA during FA maturation facilitates vinculin activation and mechanical reinforcement of FAs. Inactive vinculin localizes to the lower integrin signalling layer in FAs by binding to phospho-paxillin. Talin binding activates vinculin and targets active vinculin higher in FAs where vinculin can engage retrograde actin flow. Thus, specific protein interactions are spatially segregated within FAs at the nanoscale to regulate vinculin activation and function.
In mammals, subplate neurons (SPNs) are among the first generated cortical neurons. While most SPNs exist only transiently during development, a number of SPNs persist among adult Layer 6b (L6b). During development, SPNs receive thalamic and intra-cortical input, and primarily project to Layer 4 (L4). SPNs are critical for the anatomical and functional development of thalamocortical connections and also pioneer corticothalamic projections. Since SPNs are heterogeneous, SPN subpopulations might serve different roles. Here, we investigate the connectivity of one subpopulation, complexin-3 (Cplx3)-positive SPNs (Cplx3-SPNs), in mouse whisker somatosensory (barrel) cortex (S1). We find that many Cplx3-SPNs survive into adulthood and become a subpopulation of L6b. Cplx3-SPNs axons project to thalamorecipient layers, that is, L4, 5a, and 1. The L4 projections are biased towards the septal regions between barrels in the second postnatal week. Thus, S1 Cplx3-SPN targets co-localize with the eventual projections of the medial posterior thalamic nucleus (POm). In addition to their cortical targets, Cplx3-SPNs also extend long-range axons to several thalamic nuclei, including POm. Thus, Cplx3-SPN/L6b neurons are associated with paralemniscal pathways and can potentially directly link thalamocortical and corticothalamic circuits. This suggests an additional key role for SPNs in the establishment and maintenance of thalamocortical processing.
This protocol describes how to apply appropriate pharmacological controls to induce mitochondrial fusion or fission in studies of mitochondria morphology for four different mammalian cell types, HepG2 human liver hepatocellular carcinoma cells, MCF7 human breast adenocarcinoma cells, HEK293 human embryonic kidney cells, and collagen sandwich culture of primary rat hepatocytes. The protocol provides methods of treating cells with these pharmacological controls, staining mitochondria with commercially available MitoTracker Green and TMRE dyes, and imaging the mitochondrial morphology in live cells using a confocal fluorescent microscope. It also describes the cell culture methods needed for this protocol. © 2018 by John Wiley & Sons, Inc.
Insects, like most animals, tend to steer away from imminent threats [1-7]. Drosophila melanogaster, for example, generally initiate an escape take-off in response to a looming visual stimulus, mimicking a potential predator [8]. The escape response to a visual threat is, however, flexible [9-12] and can alternatively consist of walking backward away from the perceived threat [11], which may be a more effective response to ambush predators such as nymphal praying mantids [7]. Flexibility in escape behavior may also add an element of unpredictability that makes it difficult for predators to anticipate or learn the prey's likely response [3-6]. Whereas the fly's escape jump has been well studied [8, 9, 13-18], the neuronal underpinnings of evasive walking remain largely unexplored. We previously reported the identification of a cluster of descending neurons-the moonwalker descending neurons (MDNs)-the activity of which is necessary and sufficient to trigger backward walking [19], as well as a population of visual projection neurons-the lobula columnar 16 (LC16) cells-that respond to looming visual stimuli and elicit backward walking and turning [11]. Given the similarity of their activation phenotypes, we hypothesized that LC16 neurons induce backward walking via MDNs and that turning while walking backward might reflect asymmetric activation of the left and right MDNs. Here, we present data from functional imaging, behavioral epistasis, and unilateral activation experiments that support these hypotheses. We conclude that LC16 and MDNs are critical components of the neural circuit that transduces threatening visual stimuli into directional locomotor output.
The accelerating pace of technological advancements necessitates specialised expertise and cutting-edge instruments to maintain competitive research in life sciences. Core facilities - collaborative laboratories equipped with state-of-the-art tools and staffed by expert personnel - are vital resources that support diverse scientific endeavours. However, their adoption in lower-income communities has been comparatively stagnant due to both financial and cultural challenges. This paper explores the perils of not supporting core facilities on national research enterprises, underscoring the need for balanced investments in discovery science and crucial infrastructure support. We explore the implications from the perspectives of funders, university leaders and lab heads. We advocate for a paradigm shift to recognise these facilities as essential components of national research efforts. Core facilities are positioned not as optional but as strategic investments that can catalyse breakthroughs, particularly in environments with limited resources.
The accelerating pace of technological advancements necessitates specialised expertise and cutting-edge instruments to maintain competitive research in life sciences. Core facilities - collaborative laboratories equipped with state-of-the-art tools and staffed by expert personnel - are vital resources that support diverse scientific endeavours. However, their adoption in lower-income communities has been comparatively stagnant due to both financial and cultural challenges. This paper explores the perils of not supporting core facilities on national research enterprises, underscoring the need for balanced investments in discovery science and crucial infrastructure support. We explore the implications from the perspectives of funders, university leaders and lab heads. We advocate for a paradigm shift to recognise these facilities as essential components of national research efforts. Core facilities are positioned not as optional but as strategic investments that can catalyse breakthroughs, particularly in environments with limited resources.
To coordinate cellular physiology, eukaryotic cells rely on the inter-organelle transfer of molecules at specialized organelle-organelle contact sites1,2. Endoplasmic reticulum-mitochondria contact sites (ERMCSs) are particularly vital communication hubs, playing key roles in the exchange of signaling molecules, lipids, and metabolites3. ERMCSs are maintained by interactions between complementary tethering molecules on the surface of each organelle4,5. However, due to the extreme sensitivity of these membrane interfaces to experimental perturbation6,7, a clear understanding of their nanoscale structure and regulation is still lacking. Here, we combine 3D electron microscopy with high-speed molecular tracking of a model organelle tether, VAPB, to map the structure and diffusion landscape of ERMCSs. From EM reconstructions, we identified subdomains within the contact site where ER membranes dramatically deform to match local mitochondrial curvature. In parallel live cell experiments, we observed that the VAPB tethers that mediate this interface were not immobile, but rather highly dynamic, entering and leaving the site in seconds. These subdomains enlarged during nutrient stress, indicating ERMCSs can readily remodel under different physiological conditions. An ALS-associated mutation in VAPB altered the normal fluidity of contact sites, likely perturbing effective communication across the contact site and preventing remodeling. These results establish high speed single molecule imaging as a new tool for mapping the structure of contact site interfaces and suggest that the diffusion landscape of VAPB is a crucial component of ERMCS homeostasis.
To coordinate cellular physiology, eukaryotic cells rely on the rapid exchange of molecules at specialized organelle-organelle contact sites. Endoplasmic reticulum-mitochondrial contact sites (ERMCSs) are particularly vital communication hubs, playing key roles in the exchange of signalling molecules, lipids and metabolites. ERMCSs are maintained by interactions between complementary tethering molecules on the surface of each organelle. However, due to the extreme sensitivity of these membrane interfaces to experimental perturbation, a clear understanding of their nanoscale organization and regulation is still lacking. Here we combine three-dimensional electron microscopy with high-speed molecular tracking of a model organelle tether, Vesicle-associated membrane protein (VAMP)-associated protein B (VAPB), to map the structure and diffusion landscape of ERMCSs. We uncovered dynamic subdomains within VAPB contact sites that correlate with ER membrane curvature and undergo rapid remodelling. We show that VAPB molecules enter and leave ERMCSs within seconds, despite the contact site itself remaining stable over much longer time scales. This metastability allows ERMCSs to remodel with changes in the physiological environment to accommodate metabolic needs of the cell. An amyotrophic lateral sclerosis-associated mutation in VAPB perturbs these subdomains, likely impairing their remodelling capacity and resulting in impaired interorganelle communication. These results establish high-speed single-molecule imaging as a new tool for mapping the structure of contact site interfaces and reveal that the diffusion landscape of VAPB at contact sites is a crucial component of ERMCS homeostasis.
Functional imaging in behaving animals is essential to understanding brain function. However, artifacts resulting from animal motion, including locomotion, can severely corrupt functional measurements. To dampen tissue motion, we designed a new optical window with minimal optical aberrations. Using the newly developed high-speed continuous volumetric imaging system based on an optical phase-locked ultrasound lens, we quantified motion of the cerebral cortex and hippocampal surface during two-photon functional imaging in behaving mice. We find that the out-of-plane motion is generally greater than the axial dimension of the point-spread-function during mouse locomotion, which indicates that high-speed continuous volumetric imaging is necessary to minimize motion artifacts.