Filter
Associated Lab
- Ahrens Lab (41) Apply Ahrens Lab filter
- Aso Lab (39) Apply Aso Lab filter
- Baker Lab (19) Apply Baker Lab filter
- Betzig Lab (98) Apply Betzig Lab filter
- Beyene Lab (4) Apply Beyene Lab filter
- Bock Lab (14) Apply Bock Lab filter
- Branson Lab (45) Apply Branson Lab filter
- Card Lab (32) Apply Card Lab filter
- Cardona Lab (44) Apply Cardona Lab filter
- Chklovskii Lab (10) Apply Chklovskii Lab filter
- Clapham Lab (10) 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 (14) Apply Fitzgerald Lab filter
- Freeman Lab (15) Apply Freeman Lab filter
- Funke Lab (33) Apply Funke Lab filter
- Gonen Lab (59) Apply Gonen Lab filter
- Grigorieff Lab (34) Apply Grigorieff Lab filter
- Harris Lab (47) Apply Harris Lab filter
- Heberlein Lab (13) Apply Heberlein Lab filter
- Hermundstad Lab (17) Apply Hermundstad Lab filter
- Hess Lab (65) Apply Hess Lab filter
- Jayaraman Lab (39) Apply Jayaraman Lab filter
- Ji Lab (32) 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
- Lavis Lab (119) Apply Lavis Lab filter
- Lee (Albert) Lab (29) Apply Lee (Albert) Lab filter
- Leonardo Lab (19) Apply Leonardo Lab filter
- Li Lab (1) Apply Li Lab filter
- Lippincott-Schwartz Lab (83) Apply Lippincott-Schwartz Lab filter
- Liu (Zhe) Lab (51) 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 (3) Apply O'Shea Lab filter
- Otopalik Lab (1) Apply Otopalik Lab filter
- Pachitariu Lab (26) Apply Pachitariu Lab filter
- Pastalkova Lab (5) Apply Pastalkova Lab filter
- Pavlopoulos Lab (7) Apply Pavlopoulos Lab filter
- Pedram Lab (1) Apply Pedram Lab filter
- Podgorski Lab (16) Apply Podgorski Lab filter
- Reiser Lab (42) Apply Reiser Lab filter
- Riddiford Lab (20) Apply Riddiford Lab filter
- Romani Lab (28) Apply Romani Lab filter
- Rubin Lab (100) Apply Rubin Lab filter
- Saalfeld Lab (41) Apply Saalfeld Lab filter
- Satou Lab (1) Apply Satou Lab filter
- Scheffer Lab (36) Apply Scheffer Lab filter
- Schreiter Lab (44) Apply Schreiter Lab filter
- Shroff Lab (18) 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 (67) Apply Stern Lab filter
- Sternson Lab (47) Apply Sternson Lab filter
- Stringer Lab (21) Apply Stringer Lab filter
- Svoboda Lab (131) Apply Svoboda Lab filter
- Tebo Lab (6) Apply Tebo Lab filter
- Tervo Lab (9) Apply Tervo Lab filter
- Tillberg Lab (12) 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 (1) Apply Voigts Lab filter
- Wang (Meng) Lab (6) Apply Wang (Meng) Lab filter
- Wang (Shaohe) Lab (1) 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 (1) 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 (48) Apply FlyEM filter
- FlyLight (45) Apply FlyLight filter
- GENIE (38) 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) (21) Apply Tool Translation Team (T3) filter
- Transcription Imaging (45) Apply Transcription Imaging filter
Associated Support Team
- Anatomy and Histology (18) Apply Anatomy and Histology filter
- Cryo-Electron Microscopy (31) Apply Cryo-Electron Microscopy filter
- Electron Microscopy (10) Apply Electron Microscopy filter
- Fly Facility (39) Apply Fly Facility filter
- Gene Targeting and Transgenics (10) Apply Gene Targeting and Transgenics filter
- Integrative Imaging (10) Apply Integrative Imaging 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 (31) Apply Project Technical Resources filter
- Quantitative Genomics (18) Apply Quantitative Genomics filter
- Scientific Computing Software (56) 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 (64) Apply 2024 filter
- 2023 (178) Apply 2023 filter
- 2022 (166) Apply 2022 filter
- 2021 (174) Apply 2021 filter
- 2020 (178) 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
2432 Janelia Publications
Showing 1231-1240 of 2432 resultsControl of metabolism by compartmentation is a widespread feature of higher cells. Recent studies have focused on dynamic intracellular bodies such as stress granules, P-bodies, nucleoli, and metabolic puncta. These bodies appear as separate phases, some containing reversible, amyloid-like fibrils formed by interactions of low-complexity protein domains. Here we report five atomic structures of segments of low-complexity domains from granule-forming proteins, one determined to 1.1 Å resolution by micro-electron diffraction. Four of these interacting protein segments show common characteristics, all in contrast to pathogenic amyloid: kinked peptide backbones, small surface areas of interaction, and predominate attractions between aromatic side-chains. By computationally threading the human proteome on three of our kinked structures, we identified hundreds of low-complexity segments potentially capable of forming such reversible interactions. These segments are found in proteins as diverse as RNA binders, nuclear pore proteins, keratins, and cornified envelope proteins, consistent with the capacity of cells to form a wide variety of dynamic intracellular bodies.
It is now possible to routinely determine atomic resolution structures by electron cryo-microscopy (cryoEM), facilitated in part by the method known as micro electron-diffraction (MicroED). Since its initial demonstration in 2013, MicroED has helped determine a variety of protein structures ranging in molecular weight from a few hundred Daltons to several hundred thousand Daltons. Some of these structures were novel while others were previously known. The resolutions of structures obtained thus far by MicroED range from 3.2Å to 1.0Å, with most better than 2.5Å. Crystals of various sizes and shapes, with different space group symmetries, and with a range of solvent content have all been studied by MicroED. The wide range of crystals explored to date presents the community with a landscape of opportunity for structure determination from nano crystals. Here we summarize the lessons we have learned during the first few years of MicroED, and from our attempts at the first ab initio structure determined by the method. We re-evaluate theoretical considerations in choosing the appropriate crystals for MicroED and for extracting the most meaning out of measured data. With more laboratories worldwide adopting the technique, we speculate what the first decade might hold for MicroED.
Low dose imaging procedures are key for a successful cryoEM experiment (whether by electron cryotomography, single particle analysis, electron crystallography, or MicroED). We present a method to minimize magnetic hysteresis of the condenser lens system in the JEOL JEM-3200FSC transmission electron microscope (TEM) in order to maintain a stable optical axis for the beam path of low-dose imaging. The simple procedure involves independent voltage ramping of the CL1 and CL2 lenses immediately before switching to the focusing and exposure beam settings for data collection.
T cell activation and especially trafficking of T cell receptor microclusters during immunological synapse formation are widely thought to rely on cytoskeletal remodeling. However, important details on the involvement of actin in the latter transport processes are missing. Using a suite of advanced optical microscopes to analyze resting and activated T cells, we show that, following contact formation with activating surfaces, these cells sequentially rearrange their cortical actin across the entire cell, creating a previously unreported ramifying actin network above the immunological synapse. This network shows all the characteristics of an inward-growing transportation network and its dynamics correlating with T cell receptor rearrangements. This actin reorganization is accompanied by an increase in the nanoscale actin meshwork size and the dynamic adjustment of the turnover times and filament lengths of two differently sized filamentous actin populations, wherein formin-mediated long actin filaments support a very flat and stiff contact at the immunological synapse interface. The initiation of immunological synapse formation, as highlighted by calcium release, requires markedly little contact with activating surfaces and no cytoskeletal rearrangements. Our work suggests that incipient signaling in T cells initiates global cytoskeletal rearrangements across the whole cell, including a stiffening process for possibly mechanically supporting contact formation at the immunological synapse interface as well as a central ramified transportation network apparently directed at the consolidation of the contact and the delivery of effector functions.
Animals rely on dedicated sensory circuits to extract and encode environmental features. How individual neurons integrate and translate these features into behavioral responses remains a major question. Here, we identify a visual projection neuron type that conveys predator approach information to the Drosophila giant fiber (GF) escape circuit. Genetic removal of this input during looming stimuli reveals that it encodes angular expansion velocity, whereas other input cell type(s) encode angular size. Motor program selection and timing emerge from linear integration of these two features within the GF. Linear integration improves size detection invariance over prior models and appropriately biases motor selection to rapid, GF-mediated escapes during fast looms. Our findings suggest feature integration, and motor control may occur as simultaneous operations within the same neuron and establish the Drosophila escape circuit as a model system in which these computations may be further dissected at the circuit level.
Jumping in planthopper and froghopper insects is propelled by a catapult-like mechanism requiring mechanical storage of energy and its quick release to accelerate the hind legs rapidly. To understand the functional biomechanics involved in these challenging movements, the internal skeleton, tendons and muscles involved were reconstructed in 3-D from confocal scans in unprecedented detail. Energy to power jumping was generated by slow contractions of hind leg depressor muscles and then stored by bending specialised elements of the thoracic skeleton that are composites of the rubbery protein resilin sandwiched between layers of harder cuticle with air-filled tunnels reducing mass. The images showed that the lever arm of the power-producing muscle changed in magnitude during jumping, but at all joint angles would cause depression, suggesting a mechanism by which the stored energy is released. This methodological approach illuminates how miniaturized components interact and function in complex and rapid movements of small animals.
Theoretical calculations suggest that crystals exceeding 100 nm thickness are excluded by dynamical scattering from successful structure determination using microcrystal electron diffraction (MicroED). These calculations are at odds with experimental results where MicroED structures have been determined from significantly thicker crystals. Here we systematically evaluate the influence of thickness on the accuracy of MicroED intensities and the ability to determine structures from protein crystals one micrometer thick. To do so, we compare ab initio structures of a human prion protein segment determined from thin crystals to those determined from crystals up to one micrometer thick. We also compare molecular replacement solutions from crystals of varying thickness for a larger globular protein, proteinase K. Our results indicate that structures can be reliably determined from crystals at least an order of magnitude thicker than previously suggested by simulation, opening the possibility for an even broader range of MicroED experiments.
Many animals orient using visual cues, but how a single cue is selected from among many is poorly understood. Here we show that Drosophila ring neurons—central brain neurons implicated in navigation—display visual stimulus selection. Using in vivo two-color two-photon imaging with genetically encoded calcium indicators, we demonstrate that individual ring neurons inherit simple-cell-like receptive fields from their upstream partners. Stimuli in the contralateral visual field suppressed responses to ipsilateral stimuli in both populations. Suppression strength depended on when and where the contralateral stimulus was presented, an effect stronger in ring neurons than in their upstream inputs. This history-dependent effect on the temporal structure of visual responses, which was well modeled by a simple biphasic filter, may determine how visual references are selected for the fly's internal compass. Our approach highlights how two-color calcium imaging can help identify and localize the origins of sensory transformations across synaptically connected neural populations.
The fruit fly Drosophila melanogaster performs many behaviors, from simple motor actions to complex social interactions, that are of interest to neurobiologists studying how the brain controls behavior. Here, an undergraduate laboratory exercise uses cutting-edge methods to activate sets of neurons thermogenetically, triggering 60 different behaviors. Students learn how to recognize this large repertoire of behaviors from 16 fly strains that are publicly available, and from a large set of training videos provided here. A full protocol, timeline and handouts are included. Instructors need not have any experience working with flies. Student feedback is reported; in our experience, students are fascinated and highly engaged by watching animals perform such a broad array of behaviors. This exercise teaches fly husbandry and crossing, careful scientific observation, and principles of behavioral screening.
During active somatosensation, neural signals expected from movement of the sensors are suppressed in the cortex, whereas information related to touch is enhanced. This tactile suppression underlies low-noise encoding of relevant tactile features and the brain's ability to make fine tactile discriminations. Layer (L) 4 excitatory neurons in the barrel cortex, the major target of the somatosensory thalamus (VPM), respond to touch, but have low spike rates and low sensitivity to the movement of whiskers. Most neurons in VPM respond to touch and also show an increase in spike rate with whisker movement. Therefore, signals related to self-movement are suppressed in L4. Fast-spiking (FS) interneurons in L4 show similar dynamics to VPM neurons. Stimulation of halorhodopsin in FS interneurons causes a reduction in FS neuron activity and an increase in L4 excitatory neuron activity. This decrease of activity of L4 FS neurons contradicts the "paradoxical effect" predicted in networks stabilized by inhibition and in strongly-coupled networks. To explain these observations, we constructed a model of the L4 circuit, with connectivity constrained by in vitro measurements. The model explores the various synaptic conductance strengths for which L4 FS neurons actively suppress baseline and movement-related activity in layer 4 excitatory neurons. Feedforward inhibition, in concert with recurrent intracortical circuitry, produces tactile suppression. Synaptic delays in feedforward inhibition allow transmission of temporally brief volleys of activity associated with touch. Our model provides a mechanistic explanation of a behavior-related computation implemented by the thalamocortical circuit.