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Günter Blobel received his Nobel Prize
No full textThe Nobel Prize in Physiology or Medicine 1999 was awarded to Günter Blobel for the discovery that proteins have intrinsic signals that govern their transport and localization in the cell .
“It was for the basic science where we learned how, within a cell, proteins move from where they are made to the place where they perform their function. To greatly simplify, we found that proteins contain built-in “ZIP codes” that help them move to specific cellular addresses. Because of the ZIP coding, the proteins can traverse membranes by moving through channels to get to the areas where they are needed.” (Claudia Dreifus. A Conversation with Günter Blobel. New York Times, 2004)
Photo by Hans Mehlinhttps://digitalcommons.rockefeller.edu/blobel-molecular-biology/1042/thumbnail.jp
Günter Blobel and Laura Maioglio in Fubine Monferrato
No full textGünter Blobel and Laura Maioglio in Fubine Monferrato, 1999. Photo by Luigi Angelinohttps://digitalcommons.rockefeller.edu/blobel-molecular-biology/1063/thumbnail.jp
Brentano Quartet
No full text2018, December 7
Brentano Quartet Performing Haydn: Quartet in C Major, Op. 20 #2; Lei Liang: Gobi Gloria; Bartok: Quartet No. 2
Photo by Jürgen Frankhttps://digitalcommons.rockefeller.edu/tri-institutional-noon-recitals/1050/thumbnail.jp
Orchestra of Exiles
No full text2018, May 25th
Screening Orchestra of Exiles: The Story of Bronislaw Huberman, the Israel Philharmonic, and the One Thousand Jews He Saved from Nazi Horrors. A film screening followed by Q and A with Josh Aronson, Academy Award-nominated director and producer.https://digitalcommons.rockefeller.edu/tri-institutional-noon-recitals/1063/thumbnail.jp
Modeling Alzheimer\u27s Disease in Induced Pluripotent Stem Cells
Get PDFAlzheimer\u27s disease (AD) is the most common cause of dementia worldwide, and is now the 5th leading cause of death in the United States. The pathologic hallmarks of AD include the deposition of extracellular plaques of aggregated amyloid-β (Aβ) and intracellular neurofibrillary tangles of tau aggregates (NFTs). Autosomal dominant inheritance of AD has been attributed to genetic mutations in three key genes: amyloid precursor protein (APP), presenilin-1 (PSEN1), and presenilin-2 (PSEN-2). Together, these pathologic findings and genetics provided the framework for the amyloid cascade hypothesis, which states that Aβ deposition is a necessary, early event that is upstream of the formation of NFTs, and is causative of AD. Despite this seminal work, the mechanisms underlying the clinical progression of AD is still poorly understood. This gap in our knowledge is due, in large part, to the lack of appropriate AD disease models. Specifically, rodent models of human neurodegenerative disease fail to completely recapitulate disease phenotypes. In the body of work that follows, we utilized recent advances in induced pluripotent stem cell (iPSC) and genome editing technologies to investigate two separate AD disease mechanisms: tau spreading and Aβ production in familial AD (FAD) PSEN1 mutants. Using TALENs, we generated a transgenic donor iPSC line that harbors a transgene for inducing the expression of fluorescently tagged tau protein and a recipient iPSC line that expresses membrane anchored YFP. These cell lines, when differentiated into human cortical neurons and cultured together, demonstrated that tau is transferred between neurons. However, similar protein spreading was observed for the control cell line expressing only mCherry, suggesting that tau did not transfer by a unique mechanism in this culture system. With the hope of revealing new insights into AD mechanisms, we next used CRISPR/Cas9 to produce a series of isogenic iPSC lines that harbor discrete FAD PSEN1 mutations. These mutations in PSEN1 alter the relative amount of Aβ peptides, specifically increasing the ratio of Aβ 42:40 and Aβ 42:38. Our results demonstrate that each mutation causes a reduction in the levels of both Aβ40 and Aβ38, as well as an increase in Aβ42. These results support the model that FAD PSEN1 mutations cause a loss of protein function, in that PSEN1 cannot properly process Aβ42 into smaller, less aggregation prone peptides. Consistent with this, we found that C-terminal fragments of APP (β-CTF) accumulate in neurons with homozygous FAD mutations in PSEN1. Additionally, we also observed defects in the processing of other g-secretase substrates such as N-Cadherin. Intriguingly, the Aβ 42:40 ratio and Aβ40 levels correlated with disease onset in heterozygous mutants, while Aβ42 levels correlated with disease onset in homozygous mutants, suggesting that these values could be predictive of disease progression in culture. These results are all consistent with a partial loss in PSEN1 function, extending our current understanding of how FAD PSEN1 mutations affect PSEN1 function, and, perhaps more importantly, identifying a mechanistic perturbation that is common to the tested FAD mutations. Taken together, PSEN1 dysfunction results in production of larger, aggregation prone Aβ peptides, as well as CTFs. These insights may be important for ultimately understanding how these mutations cause FAD, which will be critical for developing effective therapeutics that slow or prevent progression of this devastating disease
Victor J. Wilson Oral History. Part 4: In the Army
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/1003/thumbnail.jp
Victor J. Wilson Oral History. Part 8: My family
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/1007/thumbnail.jp
Günter Blobel by Peter Badge
No full textNobels: Nobel Laureates photographed by Peter Badge
Photo by Lubosh Stepanekhttps://digitalcommons.rockefeller.edu/open-house-2018/1001/thumbnail.jp
Poster
No full textPoster
Idea, design - Olga Nilova, Outreach Librarian
Photo by Lubosh Stepanekhttps://digitalcommons.rockefeller.edu/open-house-2018/1000/thumbnail.jp
Part of the exhibit: Early years
No full textPart of the exhibit Günter Blobel: Pioneer of Molecular Cell Biology
Idea, design - Olga Nilova, Outreach Librarian
Photo by Lubosh Stepanekhttps://digitalcommons.rockefeller.edu/open-house-2018/1005/thumbnail.jp