5430 research outputs found
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Various Laboratory Glassware
No full textVarious laboratory glassware, circa 1920s
Courtesy of Alex Koganhttps://digitalcommons.rockefeller.edu/objects-tell-stories/1007/thumbnail.jp
Old Library Catalog. Details
No full textFragment of the old library catalog, details.
Photo by Lubosh Stepanekhttps://digitalcommons.rockefeller.edu/objects-tell-stories/1018/thumbnail.jp
A Fragment of the Original Mosaic Dome (Caspary Auditorium)
No full textA fragment of the original mosaic dome (Caspary Auditorium), 1958
When the dome was first built in 1958, it was covered with one-inch-square tiles that were hues of blue with green and white highlights. Unfortunately, within eight months of its completion, the tiles started to drop off from the effects of winter freezing and thawing. Designed by renowned architect Wallace Harrison in the 1950s, Caspary Auditorium was part of a mid-twentieth century expansion of the Rockefeller University campus. With its intimate scale, clear sightlines, and superb acoustics, Caspary provides an extraordinary musical experience. It is named for Alfred H. Caspary, an independent stockbroker whose estate provided support for the construction of four buildings on the Rockefeller campus.https://digitalcommons.rockefeller.edu/objects-tell-stories/1025/thumbnail.jp
Centennial Essay by Jules Hirsch
No full textJules Hirsch. Centennial Essay
The Rockefeller University Hospital, a unique institution that played a prominent role in biomedical discovery in the 20th century, celebrated its centennial in 2010. Rockefeller’s research hospital, which opened its doors in 1910, was the country’s first clinical research hospital – and the birthplace of clinical research in the United States. A hospital unlike any other at the time, this facility was devoted to clinical investigation and to translating laboratory discoveries into new approaches to diagnosing, treating, and preventing disease. In honor of the hospital’s centennial, The Rockefeller University has created a special website with a section entitled “Discoveries Advancing Medicine” which features vignettes describing more than 100 landmark scientific and medical advances made at Rockefeller. The materials produced for the hospital’s centennial, including a 12-minute film and an essay by Dr. Jules Hirsch chronicling the hospital’s first 50 years, were designed to highlight the institution’s mission and accomplishments, and to continue to broaden public awareness of The Rockefeller University Hospital.https://digitalcommons.rockefeller.edu/objects-tell-stories/1032/thumbnail.jp
53BP1/Shieldin Counteract DSB Resection Through Fill-In Synthesis
Full text link53BP1 is a DNA damage response (DDR) factor that gained notoriety because it determines the efficacy of PARP1 inhibitors (PARPi) in BRCA1-deficient cancers. Additionally, 53BP1 promotes end-to-end fusions of telomeres lacking end protection from the shelterin component TRF2, and facilitates end-joining at programmed breaks generated during class switch recombination in the immune system. The role of 53BP1 in double strand break (DSB) repair outside of these three well-studied contexts is less clear, though it has been proposed that 53BP1 acts as a master regulator of so-called DSB repair pathway choice, promoting classical non-homologous end-joining (cNHEJ) at the expense of homology-directed repair (HDR). In the introductory chapter to the thesis, we first discuss our current understanding of the literature regarding 53BP1 and then present an alternate view: that the features of 53BP1 have evolved to promote high-fidelity DNA repair and avoid mutagenesis. This notion is supported by the data presented in the subsequent two chapters. We demonstrate that 53BP1 and its downstream effectors RIF1 and the shieldin complex limit the generation of long 3\u27 overhangs at DSBs by recruiting CST/Polα to counteract resection, challenging the long-standing model of a block to resection by this pathway. Like loss of 53BP1/RIF1/shieldin, disruption of CST/Polα/primase reverses the hallmarks of BRCA1- deficiency. CST/Polα localize to DSBs, and we directly detect fill-in synthesis by observing shieldin/CST/Polα/primase-dependent nucleotide incorporation. We also demonstrate that tethering CST to DSBs can bypass the need for recruitment by 53BP1/shieldin. A novel shieldin mutant which fails to recruit CST was non-functional in BRCA1-deficient cells, but its function could be fully restored by chemical-induced dimerization with CST. These results indicated that in BRCA1-deficient cells, CST/Polα/primase is the major effector of 53BP1/shieldin function. After an interlude (Chapter 4) on the role of CRL4/DDB1/WDR70 in regulation of the DDR, I discuss and contextualize the new results and revisit the model of 53BP1 as a DSB escort which controls DSB processing and promotes high-fidelity repair
Intestinal CD4+T Cell Responses to Food
Full text linkDuring routine digestion and absorption of food, massive quantities of diet-derived polypeptides pass through the intestine. The intestinal immune system must maintain tolerance to these dietary antigens while still protecting against pathogens and noxious agents. Oral tolerance, a robust mechanism whereby oral administration of antigen results in both local and systemic tolerance to that antigen, is a key component of this critical homeostasis. Oral tolerance requires CD4+ T cells including specifically regulatory T cells (Tregs), however the role of intestinal CD4+ T cells and the T cell repertoire in a physiological response to food protein remains largely unexplored. To characterize intestinal T cell responses to food protein, we developed a protein antigen-free solid diet which we either supplemented with a single model food protein (OVA) or compared to complex chow diet containing diverse proteins and metabolites. We found that at steady state, chow diet promotes epithelial adaptation and cytotoxic programming of intestinal CD4+ T cells including Tregs, a pathway which is further boosted by signals from the microbiota. We also observed a strong bias towards clonal selection of mature intestinal CD4+ T cells by dietary proteins, suggesting that food antigen-specific intestinal CD4+ T cells are generated in the course of eating. Finally, we show that intestinal inflammation induced by cholera toxin (CT) led to increased tissue infiltration of CD4+ T cells, enriched for Th17 rather than epithelium-adapted cells. Protection against CT-induced food allergy was associated with clonal expansion of Tregs and reduced pro-inflammatory gene expression signature, while development of food allergy was associated with proinflammatory Th17 and immune exhaustion. Altogether, these findings suggest that highly regulated maintenance of cytotoxic epithelium adapted CD4+ T cells in addition to Tregs may be critical for preventing inappropriate immune responses to food and subsequent disease
Peggy Rockefeller Plaza
No full textPeggy Rockefeller Plaza, 2022
Photo by Juan Rodriguezhttps://digitalcommons.rockefeller.edu/campus/1091/thumbnail.jp
CRC Building
No full textCRC building, 2022
Photo by Juan Rodriguezhttps://digitalcommons.rockefeller.edu/campus/1095/thumbnail.jp
River Campus
No full textRiver Campus: View on Nurses Residence and Founder\u27s Hall, fall 2022
Photo by Juan Rodriguezhttps://digitalcommons.rockefeller.edu/river_campus/1075/thumbnail.jp
Non-Canonical Odor Coding Ensures Robust Mosquito Attraction to Humans
Full text linkAedes aegypti mosquitoes spread deadly diseases, including dengue, Zika, yellow fever, and chikungunya. Only female mosquitoes bite, and they do so because they require a blood-meal for reproduction. Aedes aegypti prefer to bite human hosts, which contributes to their effectiveness as a deadly disease vector. Mosquitoes rely heavily on chemosensory cues, including carbon dioxide (CO2) emitted from breath and human body odor, which is a mixture of more than 200 different individual odorants. Although the exact odor profile of people varies considerably, Aedes aegypti are incredibly reliable in finding humans to bite, despite widespread efforts to by humans to mask our odor. Even mosquitoes with genetic mutations that eliminate entire families of chemosensory receptors are still able to find and bite humans. It remains unknown how the mosquito olfactory system is seemingly infallible in its ability to detect humans for taking a blood meal. In the well-studied olfactory systems of Drosophila melanogaster and Mus musculus, individual olfactory sensory neurons express a single type of olfactory receptor and project their axons to discrete regions, called glomeruli, in the antennal lobe or olfactory bulb, respectively. This organization is believed to be a widespread motif in olfactory systems and has been established dogma since the mid-2000s and is hypothesized to permit the brain to parse which subpopulation of olfactory neurons is activated by a given odor. To understand how human odor is encoded in the mosquito olfactory system, we developed a CRISPR-Cas9-based genetic knock-in strategy in Aedes aegypti and generated a suite of transgenic mosquito strains that label populations of olfactory sensory neurons. Surprisingly, we find that the olfactory system of Aedes aegypti does not have the expected one-receptor-to-one-neuron-to-oneglomerulus organization seen in other insects. Rather, there are many more receptors than glomeruli. We frequently observe co-expression of multiple chemosensory receptors within individual olfactory sensory neurons and individual glomeruli are commonly innervated by olfactory sensory neurons expressing different receptors. What is the functional consequence of this unconventional organization? To understand how co-expression of multiple chemosensory families affects human odor detection by mosquitoes, we examined a minimal mixture that drives host seeking behavior. Mosquitoes are attracted to the combination of the two human-derived, cues CO2 and lactic acid. We found that the same neurons that sense CO2 also sense volatile amines, including triethyl amine. These amines are detected by separate chemosensory receptor genes and we discovered that these cues can be interchanged to drive attraction in the presence of lactic acid. This sensory organization, in which multiple receptors that respond to very different types of chemicals are co-expressed, suggests a redundancy in the odor code at the level of the olfactory sensory neurons for cues that signal the presence of a human to bite. We speculate that this design supports the robust human host-seeking seen in this olfactory specialist