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Vyacheslav Gryaznov, Piano
No full text2019, October 25
Vyacheslav Gryaznov, piano, performed Grieg-Gryaznov; from “Peer Gynt” - Morning, Anitra’s Dance; J.S. Bach: English Suite No. 2 in A Minor, BWV 807; Debussy: Suite Bergamasque; Liszt: Mephisto Waltz No.1, S. 514; Rachmaninoff: Prelude in G minor, Op. 23, No. 5https://digitalcommons.rockefeller.edu/tri-institutional-noon-recitals/1019/thumbnail.jp
Jackiw-Campbell-Tao-Kim Quartet
No full text2019, February 8
Stefan Jackiw, violin; Jay Campbell, cello; Conrad Tao, piano; Yoonah Kim, clarinet, performed Messiaen: Quartet for the End of Time.
See also Junction Triohttps://digitalcommons.rockefeller.edu/tri-institutional-noon-recitals/1042/thumbnail.jp
Oxytocin, Dopamine, and the Neuromodulation of Mating Behavior in C. Elegans
Get PDFIn the four modalities of analysis that Tinbergen describes: mechanistic, ontological, functional, and phylogenetic, I look at both the how and the why of oxytocin as a releaser of reproductive behavior. To do so, I take the wide view across 600 million years of metazoan evolution, focusing on the oxytocin-mediated mating behavior and physiology of the often-overlooked invertebrates. By looking to these simpler animals with both smaller, paired-down nervous systems and more diverse sets of mating strategies, I elucidate some of the basic and general principles of the oxytocin circuit (Chapter I). In Chapter II, I give a survey of the ethology of Caenorhabditis (nematode roundworms) mating behavior, before I delve into the experimental investigation of the oxytocin-mediated mating circuit of Caenorhabditis elegans. The compact, fully anatomically diagrammed nervous system of this organism makes it an ideal model for this study, as do the multitude of genetic, molecular, pharmacogenic, optogenetic, and imaging tools available for C. elegans. The singular most critical feature of this animal this study exploits, however, is that I can constitutively knock out the gene for its oxytocin homolog, nematocin, without compromising the health, development, or general locomotion of the animal. In Chapter III, I show that the main source of nematocin in the male\u27s copulatory apparatus (his tail), the interneuron DVA, has activity during mating that is critical for carrying it out competently. I do this by acutely silencing DVA with a heterologous histamine-gated chloride channel and its ligand just prior to mating, then by restoring mating by letting the males recover off histamine. The experiment is repeated in the nematocin-deficient males, to identify which of the behavioral phenotypes are nematocinmediated, and which are not. Next, I discuss a genetic candidate screen to look for a mechanism of nematocin action (Chapter IV). I find that nematocin mutants are epistatic to dopamine mutants, implicating them in the same circuit. The classical interpretation of the genetic result suggests that the severe defect in dopamine deficient animals is due to a dysregulation of nematocin. I then rescue mating in dopamine-deficient males by acutely silencing DVA to corroborate this. In Chapter V I investigate the activity of DVA during mating with the fluorescent calcium indicator GCaMP. I describe an activity pattern for DVA that coordinates calcium signal rises and falls with specific sub-behaviors within the mating behavior. I then look at DVA in nematocin deficient and dopamine-deficient males, and find that DVA activity breaks down at behavioral junctures consistent with the genetic behavioral data. In Chapter VI I identify 2 dopamine receptors responsible for communicating the dopamine signal to DVA, one of which is a D1-like receptor (cAMP activating) and the other of which is a D2-like receptor (cAMP suppressing), and demonstrate their reciprocal effects on mating behavior. In Chapter VII, I summarize the experimental results, contextualize the main implications, and generally discuss oxytocin and dopamine\u27s deep phylogenetic connection in modulating reproductive behavior
Examining Mechanisms Regulating Microtubule Assembly and Function
Get PDFMicrotubules are cytoskeletal polymers assembled from α and β tubulin subunits that function in essentially all cellular activities. Microtubules can act as tracks for intracellular cargo transport, are required for cilia- and flagella-based motility, and establish cell morphology in specialized cells such as neurons. In dividing cells, a bipolar spindle assembles from microtubules and partitions genetic material into two daughter cells. Proper microtubule function in these diverse contexts depends on the assembly dynamics of microtubules and their organization into specialized arrays. Both intrinsic factors including the tubulin isotype composition of microtubules and extrinsic factors including microtubule-associated proteins (MAPs) can impact microtubule assembly dynamics. However, the contribution of tubulin isotype composition to microtubule dynamics is not well understood. In the first part of this thesis, I explore the impact of specific β tubulin isotypes on microtubule dynamics. Microtubules undergo dynamic instability, an intrinsic property in which filaments in bulk equilibrium switch between periods of growth and shrinkage. The rate of polymerization and depolymerization can be quantified, as well as the frequency of switching between these states. I selected the two major β tubulin isotypes (βIIB and βIII) expressed in the vertebrate brain for examination. Using an expression and purification system developed in our lab, I generated recombinant tubulin heterodimers that were isotypically pure in β tubulin composition. I used in vitro reconstitution and total internal reflection fluorescence (TIRF) microscopy to examine the dynamics of individual microtubules assembled from these distinct heterodimers. I found that microtubules assembled with βIIB are substantially more stable, switching from a state of growth to a state of shrinkage (termed catastrophe) three-fold less frequently than their βIII-containing counterparts. These two isotypes differ substantially in the C-terminal tail, a region thought important for modulating interactions with MAPs but whose contribution to microtubule dynamics is not well understood. I found that swapping the C-terminal tails did not substantially alter dynamic instability parameters. These data reveal that isotype-specific polymerization properties are mediated by residue changes in the structured core of tubulin, rather than the divergent C-terminal tail. In the second part of the thesis, I examine the contribution of microtubule bundles to chromosome movement during anaphase. As sister chromosomes separate, a specialized array of microtubules called the spindle midzone assembles between the segregating chromosomes. Within this structure, microtubules overlap in the antiparallel orientation and are cross-linked by the non-motor MAP, Protein Regulator of Cytokinesis 1 (PRC1), forming bundles. Current models suggest that the spindle midzone can function to facilitate or restrict chromosome movement, however it is unclear how the accumulation of PRC1 on midzone microtubule bundles impact these activities. Using lattice light sheet microscopy, I examined the time-dependent changes in microtubule overlap length that accompany anaphase chromosome movement. I then selectively disrupted midzone formation by knocking down PRC1 and found that chromosome segregation distance and speed increased. These data support a model in which the spindle midzone, rather than aiding in chromosome segregation, instead restricts chromosome movement. Replacing endogenous PRC1 with a mutant that has reduced microtubule affinity reveals that the change in microtubule overlap length is coupled to the braking function of the midzone. My PhD work provides insight into two areas of microtubule assembly regulation. The studies detailed in chapters 2 and 3 reveal how changes in tubulin primary sequence impact polymerization properties of microtubules in vitro. The studies detailed in chapter 4 reveal how changes in the organization of microtubules in cells contributes to spindle function and chromosome segregation during anaphase
Chemical Biology, Biochemical and Structural Studies of MDN1, an AAA Protein Required for Ribosome Biogenesis
Get PDFCellular proteins are synthesized by ribosomes, which are ~3 MDa macromolecular complexes comprised of four ribosomal RNAs and ~80 ribosomal proteins in yeast. The biogenesis of such complicated ribonucleoprotein complexes is a highly regulated, multistep process requiring a plethora of more than 200 unique assembly factors. Energy-harnessing enzymes, such as ATPases and GTPases, are needed to remodel the precursors of ribosomes at fast time scales. Mdn1 is an essential dynein-like AAA protein (ATPases Associated with various Activities) that releases specific assembly factors from the precursors of 60S subunit of ribosomes. However, Mdn1\u27s unusually large size (~5000 amino acids in a single polypeptide) and the transient nature of intermediates of ribosome biogenesis have limited our understanding how Mdn1 remodels pre-60S particles. In addition, the limited homology of Mdn1 to other well-studied proteins, including dyneins, has restricted our understanding of its function. Here, I first combined chemical and biochemical approaches to develop and validate ribozinoindoles (Rbins) as the cell-permeable inhibitors of Mdn1, which are the first potent and selective inhibitors of ribosome biogenesis in eukaryotes. These compounds can be further used to dissect the dynamic functions of Mdn1 during the multistep process of ribosome biogenesis. In addition, I solved three cryo-EM structures of both full-length and truncated Mdn1 (resolution up to 4.0 Å) that provided the first pseudo-atomic models for Mdn1 in two distinct nucleotide states. Remarkably, Mdn1\u27s the C-terminal MIDAS domain (Metal Ion-Dependent Adhesion Site), which interacts with other ribosome assembly factors, docks onto the N-terminal AAA ring in a nucleotide state-specific manner, even though they are separated by more than 2000 aa. These data suggest that conformational changes in the AAA ring can be directly transmitted to the MIDAS domain, thereby driving the selective release of the MIDAS-bound assembly factors from the precursors of 60S subunit of ribosomes. Together, these chemical biology, biochemical and structural studies of Mdn1 reveal how an AAA protein can contribute to the dynamic ribosome biogenesis process in eukaryotes
River Campus Opening Celebration
No full textRiver Campus opening celebration, 2019
Photo by Mario Morgado
The new two-acre campus provides over 160,000 square feet of space—including laboratories, offices, conference rooms, and common areas—and was envisioned as way to replace aging lab facilities that were nearing the ends of their useful lives. By building in university-owned air rights over the FDR Drive, the project also allowed Rockefeller to expand its footprint by two acres and create a green roof accessible from the existing campus. The centerpiece of the River Campus, the 750-foot long Marie Josée and Henry R. Kravis Research Building, is designed to help foster collaboration between scientists and to be easily reconfigurable as needs evolve.https://digitalcommons.rockefeller.edu/river_campus/1079/thumbnail.jp
River Campus Opening Celebration
No full textRiver Campus opening celebration. 2019
Photo by Halkin Mason Photographyhttps://digitalcommons.rockefeller.edu/river_campus/1078/thumbnail.jp
River Campus Opening Celebration
No full textRiver Campus opening celebration, May 2019
Photo by Mario Morgadohttps://digitalcommons.rockefeller.edu/river_campus/1080/thumbnail.jp
Maxim Lando, Piano
No full text2019, October 11
Maxim Lando, piano, performing Franz Liszt: Transcendental Études (Études d\u27exécution transcendante) - No. 1 (Preludio), No. 2 (Fusées), No. 3 (Paysage), No. 4 (Mazeppa), No. 5 (Feux follets), No. 6 (Vision), No. 7 (Eroica), No. 8 (Wilde Jagd), No. 9 (Ricordanza), No. 10 (Appassionata), No. 11 (Harmonies du soir), No. 12 (Chasse-neige).https://digitalcommons.rockefeller.edu/tri-institutional-noon-recitals/1021/thumbnail.jp
Wei Luo, Piano
No full text2019, June 14th
Wei Luo, piano, performing Schubert: Drei Klavierstücke, D. 946; Chopin: Scherzo No. 2 in B–flat Minor, Op. 31; Mozart: Piano Sonata No. 10 in C Major, K. 330; Balakirev: Islamey – Oriental Fantasy in D–flat Major.
Photo credit ©2024 Steinway & Sonshttps://digitalcommons.rockefeller.edu/tri-institutional-noon-recitals/1025/thumbnail.jp