Archive Page: Professor Seth Grant

Professor Seth Grant moved to the University of Edinburgh in November 2011. We are maintaining this page as a historical record of Seth's research at the Sanger Institute. To find out the latest about the group's research, please visit the Genes to Cognition website.

Seth's primary research is on the basic mechanisms of behaviour and the diseases of the brain.

Seth graduated in Science, Medicine and Surgery from The University of Sydney. His first research was with Professor David Read in the Department of Physiology studying neurophysiological mechanisms of breathing and Sudden Infant Death Syndrome.

After his internship at Royal Prince Alfred Hospital he was a post-doctoral fellow at Cold Spring Harbor Laboratory in New York and worked on genetic basis of cancer and diabetes, with Douglas Hanahan. In 1989 he worked with Eric Kandel (Nobel Laureate 2000) at Columbia University and New York State Psychiatric Institute. Here he studied the molecular and genetic basis of learning and memory. In 1994, Seth moved to the University of Edinburgh, where he was Professor of Molecular Neuroscience and Director of the Centre for Neuroscience. He is currently at the Wellcome Trust Sanger Institute as a Principal Investigator, Honorary Professor at Cambridge University and directs the Genes to Cognition (G2C) research consortium (http://www.genes2cognition.org).

Seth's primary research is on the basic mechanisms of behaviour and the diseases of the brain. In 1992, he first used knockout mice to discover genes involved with learning and memory and synaptic plasticity and has identified many other genes since. He demonstrated in 1998 that neurotransmitter receptors control plasticity and behaviour through their associated proteins leading to the concept that multiprotein machines at synapses are master regulators of behaviour. In 2000 he first pioneered the use of proteomics in the nervous system and has discovered hundreds of new synapse proteins.

These synapse proteins are the subject of systematic study in the G2C program where their role in basic properties of brain function and disease are tested. These human brain diseases include schizophrenia, bipolar disease, Huntingtons and Alzheimers disease amongst others.

Seth has recently studied the evolution of the synapse and uncovered a new model for the evolutionary origins of the brain and how it evolved the complexity found in humans and other animals.

Selected Publications

• Characterization of the proteome, diseases and evolution of the human postsynaptic density.

  Bayés A, van de Lagemaat LN, Collins MO, Croning MD, Whittle IR, Choudhary JS and Grant SG

  Nature neuroscience 2011;14;1;19-21

  PUBMED: 21170055; PMC: 3040565; DOI: 10.1038/nn.2719

• A general basis for cognition in the evolution of synapse signaling complexes.

  Grant SG

  Cold Spring Harbor symposia on quantitative biology 2009;74;249-57

  PUBMED: 19955255; DOI: 10.1101/sqb.2009.74.033

• Neurotransmitters drive combinatorial multistate postsynaptic density networks.

  Coba MP, Pocklington AJ, Collins MO, Kopanitsa MV, Uren RT, Swamy S, Croning MD, Choudhary JS and Grant SG

  Science signaling 2009;2;68;ra19

  PUBMED: 19401593; PMC: 3280897; DOI: 10.1126/scisignal.2000102

• Targeted tandem affinity purification of PSD-95 recovers core postsynaptic complexes and schizophrenia susceptibility proteins.

  Fernández E, Collins MO, Uren RT, Kopanitsa MV, Komiyama NH, Croning MD, Zografos L, Armstrong JD, Choudhary JS and Grant SG

  Molecular systems biology 2009;5;269

  PUBMED: 19455133; PMC: 2694677; DOI: 10.1038/msb.2009.27

• Evolutionary expansion and anatomical specialization of synapse proteome complexity.

  Emes RD, Pocklington AJ, Anderson CN, Bayes A, Collins MO, Vickers CA, Croning MD, Malik BR, Choudhary JS, Armstrong JD and Grant SG

  Nature neuroscience 2008;11;7;799-806

  PUBMED: 18536710; PMC: 3624047; DOI: 10.1038/nn.2135

• Synapse-associated protein 102/dlgh3 couples the NMDA receptor to specific plasticity pathways and learning strategies.

  Cuthbert PC, Stanford LE, Coba MP, Ainge JA, Fink AE, Opazo P, Delgado JY, Komiyama NH, O'Dell TJ and Grant SG

  The Journal of neuroscience : the official journal of the Society for Neuroscience 2007;27;10;2673-82

  PUBMED: 17344405; PMC: 2851144; DOI: 10.1523/JNEUROSCI.4457-06.2007

• The proteomes of neurotransmitter receptor complexes form modular networks with distributed functionality underlying plasticity and behaviour.

  Pocklington AJ, Cumiskey M, Armstrong JD and Grant SG

  Molecular systems biology 2006;2;2006.0023

  PUBMED: 16738568; PMC: 1681474; DOI: 10.1038/msb4100041

• Proteomic analysis of in vivo phosphorylated synaptic proteins.

  Collins MO, Yu L, Coba MP, Husi H, Campuzano I, Blackstock WP, Choudhary JS and Grant SG

  The Journal of biological chemistry 2005;280;7;5972-82

  PUBMED: 15572359; DOI: 10.1074/jbc.M411220200

• SynGAP regulates ERK/MAPK signaling, synaptic plasticity, and learning in the complex with postsynaptic density 95 and NMDA receptor.

  Komiyama NH, Watabe AM, Carlisle HJ, Porter K, Charlesworth P, Monti J, Strathdee DJ, O'Carroll CM, Martin SJ, Morris RG, O'Dell TJ and Grant SG

  The Journal of neuroscience : the official journal of the Society for Neuroscience 2002;22;22;9721-32

  PUBMED: 12427827

• Proteomic analysis of NMDA receptor-adhesion protein signaling complexes.

  Husi H, Ward MA, Choudhary JS, Blackstock WP and Grant SG

  Nature neuroscience 2000;3;7;661-9

  PUBMED: 10862698; DOI: 10.1038/76615

• Enhanced long-term potentiation and impaired learning in mice with mutant postsynaptic density-95 protein.

  Migaud M, Charlesworth P, Dempster M, Webster LC, Watabe AM, Makhinson M, He Y, Ramsay MF, Morris RG, Morrison JH, O'Dell TJ and Grant SG

  Nature 1998;396;6710;433-9

  PUBMED: 9853749; DOI: 10.1038/24790

• Impaired long-term potentiation, spatial learning, and hippocampal development in fyn mutant mice.

  Grant SG, O'Dell TJ, Karl KA, Stein PL, Soriano P and Kandel ER

  Science (New York, N.Y.) 1992;258;5090;1903-10

  PUBMED: 1361685

• Long-term potentiation in the hippocampus is blocked by tyrosine kinase inhibitors.

  O'Dell TJ, Kandel ER and Grant SG

  Nature 1991;353;6344;558-60

  PUBMED: 1656271; DOI: 10.1038/353558a0