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Address at 20th Anniversary of RIMR
No full textAddress at 20th Anniversary of RIMR. Cosmopolitan Club, January 20, 1922
Courtesy of the Rockefeller Archive Centerhttps://digitalcommons.rockefeller.edu/the-evolving-campus/1024/thumbnail.jp
The Evolving Campus exhibit, details
No full textDetails of the exhibit The Evolving Campus
Idea, design - Olga Nilova, Special Collections Librarian
Photo by Lubosh Stepanekhttps://digitalcommons.rockefeller.edu/the-evolving-campus/1080/thumbnail.jp
GPCR Activation of the G Protein-Gated Inward-Rectifier Potassium Channel
Get PDFHeart rate is tightly regulated by the combined effects of the sympathetic and parasympathetic branches of the autonomic nervous system. These two branches control heart rate by stimulating different G protein-coupled receptors (GPCRs), which in turn activate ion channels that modify the electrical properties of cardiac pacemaker cells. Sympathetic stimulation accelerates heart rate through activation of beta-adrenergic receptors (βARs), which open excitatory ion channels through the stimulatory G protein (Gαs) pathway. Parasympathetic stimulation slows heart rate through activation of the muscarinic acetylcholine receptor M2 (M2Rs), which inhibits the effect of sympathetic stimulation through the inhibitory G protein (Gαi) pathway. M2Rs also release G protein beta-gamma subunits (Gβγ), which slow heart rate by activating G protein-gated inwardrectifier potassium (GIRK) channels. Interestingly, βARs also release the very same free Gβγ, but GIRK is not activated. The molecular mechanism underlying this specificity is poorly characterized. What is the molecular basis behind signaling specificity? It has been proposed that GIRK channels form a macromolecular supercomplex with Gαi-coupled receptors and G proteins, allowing released Gβγ to bind to and activate GIRK by proximity. However the evidence for the existence of the complex remains controversial. In the first part of my thesis, I challenge the supercomplex hypothesis by providing three experimental sets against the theory. First, GIRK co-localization with GPCRs shows no preference for M2Rs over β2ARs. Second, β2ARs do not activate GIRK channels even when they are co-localized. Third, neither Gαi1 nor G protein heterotrimers functionally interact with purified GIRK1/4 channels in the planar lipid bilayer system. I conclude that protein co-localization is not the underlying mechanism to explain why GIRK channels are specifically activated by Gαi-coupled receptors. I then set out to determine the molecular basis behind signaling specificity. Using electrophysiological technologies and bioluminescent resonance electron transfer (BRET) assays, I show that M2Rs catalyze release of Gβγ subunits at higher rates than β2ARs, generating higher Gβγ concentrations that activate GIRK and regulate other targets of Gβγ. The higher rate of Gβγ release is attributable to a faster GPCR-G protein association rate in M2Rs compared to β2ARs. I conclude that the activity of GIRK channels is simply determined by the efficiency of Gβγ release from GPCRs. Physiologically, only Gαi-coupled receptors can provide sufficient concentration of Gβγ to activate GIRK channels. In the second part of my thesis, I present my work on the functional characterization of Gβγ and Na+ regulation of two cardiac GIRK channels, GIRK1/4 hetero-tetramers and GIRK4 homo-tetramers. It is known that cardiac GIRK channels are composed of GIRK1/4 heterotetramers and GIRK4 homo-tetramers. However little is known about the functional difference between the two channels. Using purified proteins and the planar lipid bilayer system, I find that Na+ binding increases Gβγ affinity in GIRK4 homo-tetramers and thereby increases the GIRK4 responsiveness to G protein stimulation. GIRK1/4 hetero-tetramers are not activated by Na+, but rather are in a permanent state of high responsiveness to Gβγ, suggesting that the GIRK1 subunit functions like a GIRK4 subunit with Na+ permanently bound
Bedford Chamber Players
No full textBedford Chamber Players: Anthony Newman, director and harpsichord performed J.S. Bach: Brandenburg Concertos: Brandenburg Concerto No. 3 in G for Strings and Continuo, BWV 1048; Brandenburg Concerto No. 4 in G for Violin, 2 Flutes, Strings and Continuo, BWV 1049; Brandenburg Concerto No. 5 in D for Violin, Flute, Harpsichord, Strings and Continuo, BWV 1050; Brandenburg Concerto No. 6 in B-flat for 2 Violas, Strings and Continuo, BWV 1051https://digitalcommons.rockefeller.edu/tri-institutional-noon-recitals/1013/thumbnail.jp
Tessa Lark and Michael Thurber, Violin-Bass Duo
No full text2019, September 20
Tessa Lark and Michael Thurber, violin-bass duo performed a genre-bending blend of bluegrass, jazz, classical, including J.S. Bach, Lark, Thurber, Paul McCartney.
Photo by Lauren Desberghttps://digitalcommons.rockefeller.edu/tri-institutional-noon-recitals/1024/thumbnail.jp
Asiya Korepanova, Piano
No full text2019, April 26
Asiya Korepanova, piano, performing Beethoven: Eroica Variations - The Variations and Fugue for Piano in E-flat Major, Op. 35; Wagner- Liszt: Tannhäuser Overture; Rachmaninoff: Sonata in G Minor for Cello and Piano, Op.19 (solo piano transcription by Asiya Korepanova)https://digitalcommons.rockefeller.edu/tri-institutional-noon-recitals/1031/thumbnail.jp
Musicians from the Ravinia Festival/Steans Institute
No full text2019, April 12
Musicians from the Ravinia Festival/Steans Institute: Miriam Fried, violin; Grace Clifford, violin; Zhanbo Zhang, viola; Gabriel Martins, cello; Janice Carissa, piano, performed Timo Andres (b. 1985): Piano Trio; 1. Music Against Itself - 2. Muscle Memory (Scherzo) - 3. Coda (made of wood); Franz Schubert (1797-1828): String Quartet in A Minor, Op. 29, No. 1, D. 804 “Rosamunde”; César Franck (1822-1890): Piano Quintet in F Minor.https://digitalcommons.rockefeller.edu/tri-institutional-noon-recitals/1033/thumbnail.jp
Ignat Solzhenitsyn, Pianist and Conductor
No full text2019, March 1
Ignat Solzhenitsyn, pianist & conductor, performed Scriabin: Sonata No. 10, Op. 70; D. Scarlatti: Sonata in D Minor, K. 64: Gavotta: Allegro; Sonata in D Major, K. 140: Allegro; Sonata in F Minor, K. 365: Allegro; Sonata in A Major, K. 208: Andante e cantabile; Sonata in F Minor, K. 239: Allegro; Sonata in G Minor, K. 111: Allegro; Sonata in G Minor, K. deest: Largo; Sonata in A Major, K. 113: Allegro; Debussy: Images Book II, L. 111; Mozart: Sonata in F Major, K. 533/494https://digitalcommons.rockefeller.edu/tri-institutional-noon-recitals/1039/thumbnail.jp
Ulysses Quartet
No full text2019, February 15
Ulysses Quartet: Christina Bouey and Rhiannon Banerdt, violins; Colin Brookes, viola; Grace Ho, cello, performing Maurice Ravel: String Quartet in F Major; Leoš Janáček: String Quartet No. 2, “Intimate Letters”https://digitalcommons.rockefeller.edu/tri-institutional-noon-recitals/1041/thumbnail.jp
The Rockefeller Institute: 1930-1959
No full textAfter three decades of service, Flexner, at the age of 71, announced that he wished to retire as soon as a successor could be chosen. George Corner has summarized how things stood at the Institute in the spring of 1934: As he went to his office every day, Flexner could see the four chief buildings housing twenty-two active Members, with twelve Associate Members, about thirty Associates, and sixty Assistants and Fellows - a staff numbering more than one hundred and twenty, which he had built up from the twelve who began work with him in the temporary laboratories on Lexington Avenue... On the library shelves were an even hundred volumes of bound reprints, Studies from The Rockefeller Institute, reporting the researches of those years... and he knew that scattered through the heavy volumes were the records of achievements that placed The Rockefeller Institute in the front rank of the world\u27s scientific institutions. He knew too that its influence as a training center for the universities has been incalculable. One hundred and fifty-two persons had hone out... to become professors and associate professors in sixty-two American universities, colleges, and professional schools, and twenty to equivalent positions in seventeen foreign countries.
On October 1, 1935, Flexner\u27s resignation became effective, and his successor, Herbert Spencer Gasser, took office.https://digitalcommons.rockefeller.edu/the-evolving-campus/1029/thumbnail.jp