5430 research outputs found
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Antony van Leeuwenhoek and his “Little animals
No full textDobell, Clifford. Antony van Leeuwenhoek and his “Little animals”. London, 1932
Photo by Lubosh Stepanekhttps://digitalcommons.rockefeller.edu/alfred-cohn-collection/1008/thumbnail.jp
Robert Boyle. Tracts..., 1672
No full textTracts written by the honourable Robert Boyle... London, 1672
The book has been restored by Jennifer Jestin, book conservator
Photo by Lubosh Stepanekhttps://digitalcommons.rockefeller.edu/alfred-cohn-collection/1018/thumbnail.jp
The mathematical principles of natural philosophy
No full textNewton, Isaac. The mathematical principles of natural philosophy. London, 1729
Photo by Lubosh Stepanekhttps://digitalcommons.rockefeller.edu/alfred-cohn-collection/1023/thumbnail.jp
Blobel Laboratory. View no.3, April 2018
No full textBlobel laboratory in the Rockefeller Research Building, 2018
Photo by Lubosh Stepanekhttps://digitalcommons.rockefeller.edu/blobel-laboratory/1002/thumbnail.jp
Development. View no.18, January 2017
No full textDevelopment. Smith Hall Annex, Level C, 2017
Photo by Lubosh Stepanekhttps://digitalcommons.rockefeller.edu/development/1017/thumbnail.jp
Netrin Guides Spinal Commissural Axons to the Midline at Long Range Through the Receptors Dcc and Neogenin
Get PDFDuring neurodevelopment, commissural axons are guided to the ventral midline in a remarkably precise and stereotyped way. Netrin, a secreted laminin-related protein, provides the major attractive cue for midline guidance. It is thought to act at long-range, functioning either in solution (chemotaxis) or bound to surfaces (haptotaxis). A gradient of Netrin-1 along the dorsal-ventral axis of the spinal cord is thought to attract commissural axons to the midline, with the floor plate being a major source of diffusible Netrin. However, this view has recently been challenged. To address this controversy and determine what role, if any, floor plate-derived Netrin-1 plays in commissural axon guidance, we quantitatively examined the phenotypes of mice specifically lacking floor plate Netrin-1 expression. We observed that the loss of floor plate-derived Netrin-1 cause commissural axons to improperly project through the ventral motor column and resulted in fewer commissural axons that cross the ventral midline. The precrossing guidance defects observed at-a-distance from the floor plate supports the operation of Netrin as a long-range chemotropic factor. To complement these studies, we investigated the differential roles for Netrin-1 receptors, Dcc and Neo1. How these two Netrin receptors collaborate during midline crossing has yet to be fully examined. Using transgenic embryos that express Cre-recombinase within discrete spinal interneuron populations in combination with fluorescent reporter lines, we show that midline guidance of all commissural interneuron populations wholly depends on Netrin-1 signaling through the Dcc and Neo1 receptors. However, the genetic deletion of Dcc more severely perturbed midline guidance of the dorsal commissural neuron population compared to ventral interneurons, which predominantly express Neo1. The two populations differ in Dcc and Neo1 expression, both in terms of abundance and splice isoforms, and one of these differences could account for their differential dependence on Dcc for midline attraction. To gain better insight into other genes that regulate midline guidance of commissural neurons, I generated a novel Robo3Cre/+ mouse line to use in combination with fluorescent reporter lines to purify commissural neurons from embryonic spinal cord. Transcriptome analysis of isolated commissural neurons identified RGMb, a Neo1-specific ligand that is highly expressed by dorsal commissural neurons that could modulate Netrin signaling. Additionally, I profiled the transciptome of embryonic floor plate and characterized several floor plate-specific secreted proteins that were homologous to known guidance cues. The commissural neuron and floor plate transcriptomes will provide an invaluable starting point for testing the role of candidate guidance factors. The body of work performed here has reaffirmed the long-range nature of Netrin\u27s attractive effect, showed that distinct neuronal populations express unique levels and isoforms of Dcc and Neo1 to achieve a common guidance outcome, and identified candidate factors that may collaborate with Dcc/Neo1 and Netrin in midline guidance
Characterization and Reconstitution of S-Palmitoylated IFITM3 Antiviral Activity
Get PDFTo rapidly detect early stage infections the innate immune system maintains an assortment of pathogen recognition mechanisms interspersed throughout both the extracellular and intracellular environments. These sensors recognize key components of viral, bacterial and fungal pathogens, and stimulate an inflammatory response which leads to the expression of an extensive network of host defense proteins. One such canonical network is regulated by type I interferon. This pathway responds to viral infections by upregulating hundreds of interferon stimulated genes (ISG) critical for host immunity. One of the more pivotal proteins for viral control is interferon-induced transmembrane protein 3 (IFITM3). IFITM3 is a host protein known to play a key role in inhibiting numerous virus infections, including influenza, Dengue, West Nile, HIV and Ebola. It is active in the early stages of infection and interferes with viral fusion and content delivery to the cell cytoplasm. Despite this broad antiviral activity, the exact mechanism of IFITM3 viral fusion interference, and whether it directly interacts with the fusion environment remains unknown. To better understand the physiological conditions of IFITM3 antiviral activity, we required an improved understanding of the endogenous levels of S-fatty acylation. While earlier work in our lab has shown this post-translational modification to be critical for IFITM3 activity, it was previously impossible to distinguish between different modified populations. I therefore developed the acyl PEG exchange (APE) assay. Utilizing cysteine selective mass tags, APE detects different levels of fatty acylated cysteines within a protein population, which allows us to probe the lipidated states of endogenous proteins for the first time. Using this assay, I have shown that the majority of endogenous human IFITM3 is dually S-fatty acylated. To investigate the mechanism of IFITM3 antiviral activity, I generated recombinant, native, synthetically lipidated protein for structural and fusion-based studies. We applied an in vitro viral fusion model that detects the lipid mixing of viral envelopes with liposomes. We demonstrate that viral fusion is mitigated with the inclusion of recombinant IFITM3 liposomes. Furthermore, when IFITM3 is modified with maleimide palmitate to mimic fatty-acylation at cysteine 105, lipid mixing is inhibited more than the unmodified IFITM3. Overall, our recombinant model of viral fusion provides an in vitro approach to investigate IFITM3 function. The assay provides the first evidence that IFITM3 directly alters the membrane fusion environment, and that cysteine palmitoylation enhances protein function as well. In the future, these studies will be complemented with more accurate in vitro assays to further elucidate its critical mechanism
Victor J. Wilson Oral History. Part 3: The memorable year of 1953
No full textInterview recorded on December 21st, 2017. Part of the Rita and Frits Markus Library Oral History project.https://digitalcommons.rockefeller.edu/victor-wilson/1002/thumbnail.jp
Laura Maioglio Blobel
No full textLaura Maioglio Blobel
Photo by Lubosh Stepanekhttps://digitalcommons.rockefeller.edu/open-house-2018/1002/thumbnail.jp
Bird\u27s eye view of Trinity College
No full textBird\u27s eye view of Trinity College, Cambridge, c. 1687
Trinity College, Barrows’s residence for many years as student, scholar, professor, and Master. The Master’s Lodge is located on the far side of Trinity’s Great Court, while the set of his protégé, Isaac Newton, was located between the College’s main gate and its chapel
(From David Logan Cantabrigia Illustrata, 1690)https://digitalcommons.rockefeller.edu/alfred-cohn-collection/1005/thumbnail.jp