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Books on a History of The Rockefeller University
No full textTwo books on the history of The Rockefeller University:
Hanson, Elizabeth. The Rockefeller University Achievements. A Century of Science for the Benefit of Humankind, 1901–2001
Full text
Corner, George W. A History of The Rockefeller Institute 1901-1953. Origins and Growth
Full texthttps://digitalcommons.rockefeller.edu/objects-tell-stories/1002/thumbnail.jp
Journal Club Dinner
No full textJournal Club Dinner, circa 1934/1935
This film was taken by James M. Neill who worked at the Rockefeller Institute in the 1920s with Dr. Van Slyke. At the time of the film, he was a Professor of Bacteriology at Cornell Medical School. An amateur photographer, he must have been visiting former colleagues at the Institute carrying along his camera. Among the people pictured in this 3-minute footage are Oswald Avery, who with his colleagues Collin M. MacLeod and Maclyn McCarty made a discovery that DNA is the substance that transmits hereditary information; Rufus Cole, the first Director of the Rockefeller Hospital; Alexis Carrel, the first Nobel Prize winner in the history of The Rockefeller University; Alphonse Dochez, who together with Rufus Cole had developed a serum against Type 1 pneumococcus.
Donated by William Neillhttps://digitalcommons.rockefeller.edu/objects-tell-stories/1011/thumbnail.jp
Two Books From the Collection of Dr. Alfred E. Cohn
No full textTwo books from the collection of Dr. Alfred E. Cohn
The books which Dr. Cohn had collected and treasured throughout his life were bequeathed to the Rockefeller Institute where he spent most of his scholarly career. This magnificent collection includes some of the major works of many of the great names in the history of medical science: Celsus, Thomas Bartholinus, G. Borelli, Malpighi, Leuwenhoek, Richard Lower, Mead, Harvey, and many others.https://digitalcommons.rockefeller.edu/objects-tell-stories/1009/thumbnail.jp
To Alfred Cohn From His Friends in Honor of His 60th Birthday
No full textTo Alfred Cohn from his friends in honor of his 60th Birthday, 1939https://digitalcommons.rockefeller.edu/objects-tell-stories/1013/thumbnail.jp
Objects Tell Stories
No full textThe exhibit Objects Tell Stories is on view at Level A (Welch Hall)
Idea, design: Olga Nilova, Special Collections Librarian
Photo by Lubosh Stepenakhttps://digitalcommons.rockefeller.edu/objects-tell-stories/1020/thumbnail.jp
The Genetic and Neural Basis of Sexual Dimorphism in Mosquito Behavior
Full text linkOnly female mosquitoes of the species Aedes aegypti have evolved to hunt humans in order to feed on their blood. In striking contrast, male mosquitoes have no drive to seek hosts or drink their blood. Through the act of blood-feeding, only female mosquitoes can transmit pathogens that cause deadly diseases like dengue, chikungunya, and Zika. The genetic and neural circuit basis of this striking sex difference in behavior, one that is of critical importance to global public health, remain poorly characterized. Across the insects, sex-specific alternative splicing is known to control sex-specific morphological and behavioral traits. We took advantage of this knowledge to conduct an unbiased comparative transcriptomic screen and identified a number of genes that are alternatively spliced between the brains of males and females across blood-feeding mosquito species. Two of these genes were specifically expressed in the nervous system. The first gene, fruitless, encodes a set of male-specific transcription factors well-known to be required for male-specific mating behavior in Drosophila and other insects. We used CRISPR-Cas9 to generate fruitless mutant Aedes aegypti mosquitoes and found that these mutants are unable to mate, consistent with the ancestral function of this gene. Surprisingly, fruitless mutant male mosquitoes also gained a strong and specific attraction to a live human subject that was specifically elicited by human odor, and not heat or other human cues. fruitless mutant males did not gain the ability to blood-feed, suggesting that it is specifically required to inhibit attraction to humans in male mosquitoes and that other genes specify host-seeking in both male and female mosquitoes. These results indicate that fruitless, a conserved gene, has gained a new and unexpected function over the course of evolution, acting to repress host-seeking behavior in male mosquitoes. The second gene identified from this screen, the previously undescribed 11211, is sex-specifically spliced into a predicted short female and long male protein isoform, which we showed localizes to the nucleus in both sexes. With the notable exception of non-mosquito flies, 11211 orthologs are sex-specifically spliced in other insects such as bees and beetles. However, in contrast to the mosquito, all other insects encode longer female and shorter male 11211 protein isoforms, suggesting that sex-specific splicing of this gene has evolved a new role in the mosquito. In mosquitoes, but not in other insects, 11211 is enriched in neurons in a part of the brain known to control feeding behavior. We found that these neurons show sexual dimorphism in their inputs, as female 11211-expressing neurons receive input from sensory neurons that detect the taste of blood. When we silenced the activity of these 11211-expressing neurons, females were able to feed on nectar and retain an attraction to humans, but strikingly lost the ability to initiate blood feeding. These results suggest that a rapidly-evolving novel gene marks a population of neurons that are specifically required for blood-feeding behavior
B Cell Receptor Signalng in Germinal Centers
Full text linkGerminal centers (GC) are sites of B cell clonal expansion, diversification, and antibody affinity selection. This process is limited and directed by T follicular helper cells that provide helper signals to B cells that endocytose, process, and present cognate antigens in proportion to receptor affinity. GCs play a crucial role in immunity by generating an evolving B cell pool that serves as the origin of protective memory B and plasma cells. Therefore, understanding how the GC reaction is controlled and how high-affinity clones are selected within the GC is fundamental to our understanding of adaptive immunity and of crucial importance to the development of vaccines. Under current models, GC selection is primarily determined by the antigen capture function of the B cell receptor (BCR). However, the BCR can also function as a signaling entity, and it is not well understood how signaling by the B cell receptor contributes to selection. The critical barriers to addressing this question have been a lack of specific BCR signaling reporters and models that do not compromise the initiation and maintenance of the GC reaction. In the first part of my thesis, I developed and characterized a tracker to detect active antigen engagement in vivo. Crucially, this tracker does not confer any cognate antigen for presentation, thus uncoupling the signaling and antigen capture functions of the BCR. In the second part of my thesis, I used this tracker in combination with a c-Myc reporter to investigate the role of BCR signaling in positive selection. I found that BCR signaling itself enhanced the ability of cells to receive T cell help, even when antigen presentation had been normalized. Transcriptome analysis showed that continuous BCR engagement was necessary for full induction of positive selection pathways and identified a subset of pre-memory B cells associated with lower magnitudes of positive selection. GC BCR engagement per se also induces metabolic changes that may prime cells to receive T cell help. To investigate the role of BCR selection in negative selection and survival, I developed a Bruton\u27s tyrosine kinase (BTK) drug-resistant mouse model. I found that continuous BCR engagement was necessary for the survival of light zone B cells and that survival was intrinsic to BCR signaling by inhibiting BTK. Lastly, I investigated the synergy between BCR signaling and T cell help in the presence of antigen targeting and low levels of drug treatment. Dampening of BCR signaling impacted the proliferation of cells after migration, despite normalized antigen presentation capacity. In summary, selection in the GC is dependent on both the signaling and endocytic functions of the BCR
New Roles for the Integrated Stress Response in Cancer and Proteostasis
Full text linkThe integrated stress response (ISR) is a highly conserved pathway that senses diverse stresses and responds by limiting total protein synthesis and redirecting translation to stress response transcripts. The ISR has the potential to modify a broad range of processes in cancer, but the major cancer-relevant functions of the pathway have remained elusive due to the complex and redundant nature of the upstream kinases that sense stress and activate the pathway. To overcome this challenge, we genetically targeted the central, regulatory node of the pathway, eIF2α-serine 51, directly, in primary squamous cell carcinoma cells to generate ISR-null SCCs. We surprisingly found that the ISR acted as a tumor suppressor early in tumorigenesis, but also promoted proteostasis in response to the chemotherapy and proteasome inhibitor, bortezomib. We found this second finding to be mechanistically linked to a previously-undescribed role for the ISR in regulating the microtubule cytoskeleton to promote the removal of aggregated proteins. As a second goal of this project we sought to develop small molecule inhibitors of the ISR for anticancer therapy, focusing on the alternative translation initiation factor, EIF2A, which we previously found to be critical for oncogenesis. Utilizing dual luciferase reporters for alternative translation (Atf4-firefly) and housekeeping translation (HBB-renilla) we performed a high throughput screen and have identified promising hits with potential as novel EIF2A inhibitors
Nonlinear Representation of Auditory Stimuli Across the Auditory Cortex
Full text linkThe neural evoke activity to pure tones in primary auditory cortex has been systematically studied for many years, as has the spatial organization of these responses. Unlike pure tones, natural sounds possess complex spectro-temporal structures across frequencies. How simple tuning properties scale across ensembles of neurons to represent more complex sensory environments is still a question of active investigation and debate. To better understand the coding principles used to represent complex auditory sounds, we performed 2-photon calcium imaging of neural activity of the entire auditory cortex in awake mice, while playing sounds composed of single or multiple frequencies. While we observed simple tuning in response to single frequency stimuli, the calcium responses to combinations of tones displayed characteristic nonlinearities. Moreover, we could not reconstruct the multi-tone response from the responses to the individual constituent tones alone. The subset of neurons most exhibiting such nonlinearities were found to perform certain fuzzy logic operations, on the input signal and were topographically organized across the auditory cortex. Such neurons increased the effective dimensionality of the sensory representation, enhancing the decodability and classification of complex stimuli. Together, our results reveal that the auditory cortex contains a topographical map of spatially-clustered computational ensembles able to detect specific combinations of spectral features. We further hypothesize that local non-linear computations such as these may contribute to high dimensional representation across different sensory modalities
Objects Tell Stories
No full textThe exhibit Objects Tell Stories is on view at Level A (Welch Hall)
Idea, design: Olga Nilova, Special Collections Librarian
Photo by Lubosh Stepenakhttps://digitalcommons.rockefeller.edu/objects-tell-stories/1000/thumbnail.jp