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Salk Institute
Scientists and Research
Gerard  Manning

Gerard Manning

Senior Staff Scientist
Razavi-Newman Center for Bioinformatics

We, and all of modern life, are the results of over a billion years of evolutionary experimentation and selection carried out on our genomes. The current explosion of genome sequencing means that now, for the very first time, we can read out the results of these experiments and decipher the logic and diversity of sequence evolution.

We are exploring this rich, but still confusing trove of genome information using protein kinases, a set of genes that constitute about 2% of eukaryotic genes, but alter the behavior of up to 30% of all cellular proteins, and control the majority of biological pathways. They are among the most experimentally characterized of proteins and are a major class of drug targets.

By tracking the evolution of many classes of protein kinases in sequenced genomes, we aim to understand the evolutionary history of this group and relate that to organismal biology, and practical interventions in experimental research and medical therapies. We are applying our focused discoveries with kinases to other gene families, to improve gene models, orthology and better understand evolution and function.

Other research interests include microbial genomics and metagenomics, aging and neurodegeneration, and the comparative genomics of promoters and gene expression in vertebrates and model systems.

We also run a collaboration and support service to bring bioinformatics technologies to labs throughout the Salk, including research collaborations with several Salk investigators.

Education

  • B.Sc., First Class Honors, National University of Ireland, Cork
  • Ph.D., Stanford University

Selected Publications

  • Mair, W, Morantte, I, Rodrigues, AP, Manning, G, Montminy, M, Shaw, RJ, Dillin, A. Lifespan extension induced by AMPK and calcineurin is mediated by CRTC-1 and CREB. Nature 470:404-8
  • Srivastava, M, ... Manning, G, Degnan, B, Rokhsar, DS. The genome of the haplosclerid demosponge Amphimedon queenslandica and the evolution of animal complexity. Nature, 466:720-726
  • Manning G, Scheeff E. How the vertebrates were made: selective pruning of a double-duplicated genome. BMC Biology, 8:144
  • Scheeff, ED, Eswaran, J, Bunkoczi, G, Knapp, S, Manning, G. Structure of the pseudokinase VRK3 reveals a degraded catalytic site, a highly conserved kinase fold, and a putative regulatory binding site. Structure 17:128-38
  • Hutt, DM, Herman, D, Rodrigues, APC, Noel, S, Pilewski, J, Matteson, J, Kellner, W, Kelly, JW, de Jonge, HR, Riordan, JR, Sorscher, E, Frizzell, RA, Manning, G, Gottesfeld, JM, Balch, WE. Epigenomic Correction of Cystic Fibrosis through HDAC Modification. Nature Chemical Biology, 6:25-33
  • Manning, G, Young, SL, Miller, WT, Zhai, Y (2008). The protist, Monosiga brevicollis, has a tyrosine kinase signaling network more elaborate and diverse than found in any known metazoan. PNAS, 105: 9674-79
  • King, N, et al (2008) The genome of the choanoflagellate Monosiga brevicollis and the origins of metazoan multicellularity. Nature 451, 783-788
  • Vilar, M, Chou, H-T, Luhrs, T, Maji, S, Riek-Loher, D, Verel, R, Manning, G, Stahlberg, H, Riek, R. (2008) The Fold of α-Synuclein Fibrils. PNAS 105:8637-42
  • Natarajan, K, Taylor, S, Zhai, Y, Venter, C, Manning, G (2007). Structure and function of the microbial kinome. PLoS Biol. 5(3): e17
  • Yooseph, S. et al (2007). The Sorcerer II Global Ocean Sampling Expedition: Expanding the Universe of Protein Families. PLoS Biology. 5(3): e16
  • Sea Urchin Genome Sequencing Consortium. The genome of the sea urchin Strongylocentrotus purpuratus. Science 314(5801):941-52.
  • Bradham, CA, ..., Manning, G. (2006). The Sea Urchin Kinome: A First Look. Dev. Biol. 300(1):180-93.
  • Eisen JA, et al (2006). Shotgun sequencing and analysis of the macronuclear genome of the model eukaryote, the ciliate Tetrahymena thermophila.PLoS Biol. 4 (9): e286.
  • Caenepeel, S, Charydczak, G, Sudarsanam, S. Hunter, T., Manning, G. 2004. The Mouse Kinome: Discovery and comparative genomics of all mouse protein kinases. PNAS 101(32), 11707-12.
  • Manning, G, Whyte, D, Martinez, R. Hunter, T, Sudarsanam, S. 2002. The protein kinase complement of the human genome. Science 298:1912-1934.
  • Manning, G, Plowman, G, Hunter, T, Sudarsanam, S 2002. Evolution of protein kinase signaling from yeast to man. Trends in Biochemical Sciences 27(10), 514-20.

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