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Gleb Ivanov, Piano
No full text2018, November 30
Gleb Ivanov, piano, performed Haydn: Sonata in F Major, Hob. XVI 23; Rachmaninoff: Vocalise (arr. by Yurovskiy); Debussy: L′isle joyeuse, L. 106; Mussorgsky: Pictures at an Exhibition (arr. by Horowitz).
Prior to winning first prize in the 2005 Young Concert Artists International Auditions, Ivanov won the top prizes at the 1994 and 1996 International Classical Legacy Competitions in Moscow, the Laureate Prize at the 1997 Moscow International Festival for Young Soloists and the prize for best performance of a Beethoven sonata at the first International Vladimir Horowitz Competition in Kiev, Ukraine, in 1995.
A native of Moscow, Ivanov was born into a family of musicians and began to accompany his father’s vocal recitals at age 8. He graduated from the Moscow Conservatory and went on to earn his master’s degree from the Manhattan School of Music. Ivanov was a protégé of the late Mstislav Rostropovich.https://digitalcommons.rockefeller.edu/tri-institutional-noon-recitals/1051/thumbnail.jp
Pearl Meister Greengard Prize Program
No full textPearl Meister Greengard Prize program, 2018
Paul Greengard used his Nobel Prize honorarium to help fund the Pearl Meister Greengard Prize, an award for women scientists. The award is named after his mother, who died during childbirth. It was established in 2004 to shine a spotlight on exceptional women in science, since, as Greengard observed, [women] are not yet receiving awards and honors at a level commensurate with their achievements. The annual prize is awarded to an outstanding woman conducting biomedical research.https://digitalcommons.rockefeller.edu/paul-greengard-a-pioneering-neuroscientist/1045/thumbnail.jp
CONSTRUCTION 2018, MAY
No full textConstruction site: north side of River Campus with President\u27s House and Smith Hall in the background
Photo by Olga Nilovahttps://digitalcommons.rockefeller.edu/river_campus/1062/thumbnail.jp
A High-Throughput Approach to Uncover Novel Roles of APOBEC2, a Functional Orphan of the AID/APOBEC Family
Get PDFAPOBEC2 is a member of the AID/APOBEC cytidine deaminase family of proteins. Unlike most of AID/APOBEC, however, APOBEC2\u27s function remains elusive. Previous research has implicated APOBEC2 in diverse organisms and cellular processes such as muscle biology (in Mus musculus), regeneration (in Danio rerio), and development (in Xenopus laevis). APOBEC2 has also been implicated in cancer. However the enzymatic activity, substrate or physiological target(s) of APOBEC2 are unknown. For this thesis, I have combined Next Generation Sequencing (NGS) techniques with state-of-the-art molecular biology to determine the physiological targets of APOBEC2. Using a cell culture muscle differentiation system, and RNA sequencing (RNA-Seq) by polyA capture, I demonstrated that unlike the AID/APOBEC family member APOBEC1, APOBEC2 is not an RNA editor. Using the same system combined with enhanced Reduced Representation Bisulfite Sequencing (eRRBS) analyses I showed that, unlike the AID/APOBEC family member AID, APOBEC2 does not act as a 5-methyl-C deaminase. Finally, using a combination of biochemical, Chromatin Immunoprecipitation Sequencing (ChiP-Seq) and polyA RNA-Seq analyses I show that APOBEC2 is a (negative) regulator of gene expression (at least in muscle cells) and binds chromatin directly to inhibit transcription of genes involved in muscle cell differentiation. While the precise mechanism behind this activity is still a matter of investigation, this role of APOBEC2 in inhibiting genes involved in cell cycle exit, might have implications for its role in in cancer
Cell Cycle Control by Cyclin-CDKS in Chlamydomonas Reinhardtii
Get PDFThe cell cycle consists of a series of events, including replication and segregation of the genome, that occurs in order to ensure successful reproduction of cells. In fungi and animals, this process is carefully regulated by a set of protein complexes with alternating, oscillating activity. A well established model has been developed for animals and fungi in which the activities of various cyclin-dependent kinases (CDKs) and the anaphase promoting complex (APC) drive the events of the cell cycle at the appropriate time and in the appropriate order. While this model has been extremely useful for understanding cell division in these lineages, it is not necessarily applicable to other groups of eukaryotes. Animals and fungi belong to a relatively recently diverged group called the Opisthokonts, so their shared features do not necessarily extend to their eukaryotic cousins, including plants, a very important lineage of particular concern to humanity. Chlamydomonas reinhardtii is a unicellular member of the plant kingdom. Its simple genome (compared to land plants) and easily observed cell division cycle have facilitated the collection of a large number of conditional mutations that block the cell cycle at high temperature. Mutations in two CDKs, CDKA1 and CDKB1, and two subunits of the APC are included in this set. The phenotypes of these mutants at restrictive-temperature revealed that CDKA1, unlike its ortholog in the Opisthokonts, is not required for mitosis, and instead plays a role in cell cycle initiation. CDKB1, on the other hand, is a plant-specific CDK and is required for promoting the events of mitosis. The APC plays a similar role to its counterpart in Opisthokonts in driving the metaphase-to-anaphase transition. In this thesis, we present the results of our efforts to better understand the function and regulation of the kinases CDKA1 and CDKB1 and two Chlamydomonas cyclins, CYCA1 and CYCB1. We characterize the role of these molecules in cell division timing, DNA replication, spindle formation, and cytokinesis and explore the nature of their regulatory interactions and their control by the APC. We also describe a genetic screen to identify parallel pathways that promote cell cycle initiation alongside CDKA1 and speculate on a possible common thread among the identified mutations. A genetic screen for genes involved in cell cycle initiation uncovers many null mutations in CDKA1, showing definitively that CDKA1 is inessential for cell division in Chlamydomonas, and likely all plants. Disruption of both CDKA1 and CYCA1 results in a delay in cell division, and CYCA1 is specifically required for biochemical activity of CDKA1, suggesting they may act as a complex to promote the initiation of cell division. CYCB1 is required for timely DNA replication and mitotic spindle formation in a similar manner to CDKB1, and, consistently, is also required for biochemical activation of CDKB1. We propose that CYCB1 and CDKB1 form a complex and together constitute the primary mitotic inducer in Chlamydomonas. Both CDKA1 and CDKB1 are downregulated by the APC, and CDKA1 kinase activity is inhibited by CYCB1- CDKB1. A model is presented incorporating these and prior findings concerning the function and regulatory interaction among these cell cycle regulators. Several possible positive and negative feedback loops become apparent which may ensure switch-like activation or appropriate ordering of the activity of various complexes
Investigating Genetic (IN)Compatibility Between Temperate Phages and CRISPR-CAS Systems in Staphylococcus Aureus
Get PDFProkaryotic organisms employ various mechanisms for defending against parasitism by viruses and other mobile genetic elements. One form of defense comprises the adaptive immune systems derived from clustered, regularly interspaced, short palindromic repeat (CRISPR) loci and CRISPR-associated (cas) genes. CRISPR-Cas immune systems enable the acquisition of heritable resistance to specific mobile genetic elements on the basis of nucleic acid sequence recognition, but do not necessarily discriminate between target elements which are burdensome and those which are beneficial. My thesis is concerned with the consequences of CRISPR-Cas immunity directed at a particular breed of bacterial DNA viruses, known as temperate phages, which cause both harmful (lytic) and benign (lysogenic) infections under different conditions. Initial studies investigating prokaryotic CRISPR-Cas immunity seemed to indicate that functional, DNA-targeting systems cannot stably co-exist with their target elements in vivo. For example, in studies where immunity was directed at temperate phages, DNA-targeting CRISPR-Cas systems were found to prevent both lysogenic and lytic infections except when targeting was altogether abrogated via mutation or inhibition of the CRISPR-Cas system. The first part of my thesis work includes in vivo experiments which challenged the generality of this view, with regard to the different types of DNA-targeting CRISPR-Cas systems. Namely, I demonstrated that a staphylococcal branch of the \u27type III\u27 CRISPR-Cas systems is capable of tolerating lysogenic infections by specific temperate phages which are otherwise targeted during lytic infections. I further established that the capacity for conditional temperate phage tolerance results from a transcription-dependent targeting modality which was not anticipated for this particular DNA-targeting type III system. In contrast, I observed only the expected genetic escape outcomes when temperate phages were targeted by a \u27type II\u27 CRISPR-Cas system with a transcription-independent (Cas9-based) DNA targeting modality. These findings laid the groundwork for subsequent studies of CRISPR-Cas immunity to phages in Staphylococcus aureus hosts, and guided my colleagues towards in vitro characterization of the type III system\u27s transcription-dependent targeting mechanism. CRISPR-Cas systems have been identified in about 50% of sequenced bacterial genomes, and the factors which influence this distribution are still not fully understood. My description of conditional tolerance by a staphylococcal, type III CRISPR-Cas system illustrated that, in principle, these particular systems could stably co-exist with their temperate phage target elements in lysogenic hosts while maintaining their ability to protect against lytic infections. During the second part of my thesis work, I set out to define additional phenotypic consequences for the lysogenized lineages of S. aureus which maintain conditional tolerance, in an effort to better understand how this phenomenon might influence the distribution and stability of type III systems among natural isolates. Notably, I found that the maintenance of certain temperate-phage-targeting systems can incur fitness costs in lysogenic populations. I showed, furthermore, that these costs are potentially greater if more than one temperate phage is targeted in populations of double lysogens, but that they can be alleviated by mutations which do not abrogate phage targeting during lytic infections. Collectively, these findings imply that long-term maintenance of type III systems in natural populations of lysogens might require additional evolutionary fine-tuning, particularly among lineages which are prone to multiple infection
Targeting the CD4 Binding Site of HIV
Get PDFThe immunologic obstacles to develop a broadly neutralizing antibody (bNAb) against HIV by vaccine mandate for methodical testing in order to understand and direct the immune response. A mouse model with the predicted human heavy chain variable domain of a bNAb precursor or mature version introduced into the mouse heavy chain immunoglobulin locus proved to be very useful. The immunoglobulin heavy-chain of the predicted germline (GLVH) or mature mutated (MuVH) version of 3BNC60 was knocked into the JH4 locus in mice. 3BNC60 is a bNAb that targets the CD4 binding site (CD4bs) of HIV-1 and belongs to the IgHV1-2 class of broadly neutralizing CD4bs antibodies. In the first part of my thesis I will describe the evolution of the HIV-1 antibody response in GLVH and MuVH mice upon immunization. We immunized the mice with antigens designed to bind to the predicted unmutated precursor of 3BNC60 or with BG505 SOSIP trimers that resemble the native HIV-1 Env. Immunogens specifically designed to activate B cells bearing germline antibodies initiate immune responses, but they do not elicit bNAbs. In contrast, native-like Env trimers fail to activate B cells expressing germline antibodies but elicit bNAbs by selecting for a restricted group of light chains bearing specific somatic mutations that enhance neutralizing activity. The data suggest that vaccination to elicit broad anti-HIV-1 antibodies will require immunization with a succession of related immunogens. Although CD4bs bNAbs are attractive candidates for immunogen design, their features, such as a high degree of somatic hypermutation and a short CDRL3 in combination with our data in 3BNC60 knock-in mice suggest that they might be difficult to elicit through vaccination. In the second part I will describe IOMA, a new class of CD4-mimetic bNAb derived from the VH1-2 germline but with a normal-length CDRL3 and fewer somatic hypermutations than other bNAbs of its class. We defined IOMA\u27s complete epitope, by using crystal structures of a natively glycosylated Env trimer. Analysis of the native glycan shield on HIV-1 Env allowed us to provide what is, to our knowledge, the first full description of the interplay between heterogeneous untrimmed high-mannose and complex-type N-glycans within the CD4bs and of a natively glycosylated trimer
Marjorie McCarty Oral History. Part 1: Family
No full textInterview recorded on September 14th, 2017. Part of the Rita and Frits Markus Library Oral History project.https://digitalcommons.rockefeller.edu/marjorie-mccarty/1000/thumbnail.jp
Marjorie McCarty Oral History. Part 9: Active Retirement
No full textInterview recorded on October 11th, 2017. Part of the Rita and Frits Markus Library Oral History project.https://digitalcommons.rockefeller.edu/marjorie-mccarty/1009/thumbnail.jp
Victor J. Wilson Oral History. Part 1: Escaping Nazi Germany
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/1000/thumbnail.jp