Lysimachos Zografos PhD

Lysimachos Zografos


Publications:
2016
  Functional characterisation of human synaptic genes expressed in the Drosophila brain
Zografos, L, Tang, J, Hesse, F, Wanker, EE, Li, KW, Smit, AB, Davies, RW & Armstrong, JD 2016, 'Functional characterisation of human synaptic genes expressed in the Drosophila brain' Biology Open, vol 5, no. 5, pp. 662-667. DOI: 10.1242/bio.016261
Drosophila melanogaster is an established and versatile model organism. Here we describe and make available a collection of transgenic Drosophila strains expressing human synaptic genes. The collection can be used to study and characterise human synaptic genes and their interactions and as controls for mutant studies. It was generated in a way that allows the easy addition of new strains, as well as their combination. In order to highlight the potential value of the collection for the characterisation of human synaptic genes we also use two assays, investigating any gain-of-function motor and/or cognitive phenotypes in the strains in this collection. Using these assays we show that among the strains made there are both types of gain-of-function phenotypes investigated. As an example, we focus on the three strains expressing human tyrosine protein kinase Fyn, the small GTPase Rap1a and human Arc, respectively. Of the three, the first shows a cognitive gain-of-function phenotype while the second a motor gain-of-function phenotype. By contrast, Arc, which has no Drosophila ortholog, shows no gain-of-function phenotype.
General Information
Organisations: Edinburgh Neuroscience.
Authors: Zografos, Lysimachos, Tang, Joanne, Hesse, Franziska, Wanker, Erich E., Li, Ka Wan, Smit, August B., Davies, R. Wayne & Armstrong, J. Douglas.
Number of pages: 6
Pages: 662-667
Publication Date: 15 May 2016
Publication Information
Category: Article
Journal: Biology Open
Volume: 5
Issue number: 5
ISSN: 2046-6390
Original Language: English
DOIs: 10.1242/bio.016261
2012
  Reconstructing Models from Proteomics Data
Zografos, LA, Pocklington, A & Armstrong, D 2012, Reconstructing Models from Proteomics Data. in N Le Novère (ed.), Computational Systems Neurobiology. vol. VIII, Springer Netherlands, pp. 23-80. DOI: 10.1007/978-94-007-3858-4
The synaptic proteome is a highly complex and dynamic structure composed of more roughly 2,000 distinct proteins. The constant improvement of synaptic fraction preparation, protein complex isolation and mass spectrometry identification methods has led to a great accumulation of synaptic proteomics data. In order to gain a better insight of how the synaptic proteome is organised in molecular complexes identified from the biochemical analysis of neural tissues we have developed and combined a series of methods for reconstructing and analysing protein interaction network models from synaptic proteomics data. These methods cover every aspect of the reconstruction, ranging from how to annotate the proteins and acquire the protein interaction data to how to interpret and analyse the resulting models. This chapter gives a detailed overview of these methods as well as example applications to case study proteomics datasets.
General Information
Organisations: Institute for Adaptive and Neural Computation .
Authors: Zografos, Lysimachos A., Pocklington, Andrew & Armstrong, Douglas.
Pages: 23-80
Publication Date: 2012
Publication Information
Category: Chapter (peer-reviewed)
Original Language: English
DOIs: 10.1007/978-94-007-3858-4
2010
  Comparative Bioinformatics Studies Of Mammalian and Insect Postsynaptic Density Complexes and Interaction Networks
Zografos, LA, Pocklington, A, Grant, SGN & Armstrong, D 2010, 'Comparative Bioinformatics Studies Of Mammalian and Insect Postsynaptic Density Complexes and Interaction Networks'.
The postsynaptic density (PSD) is a multi-protein complex, consisting of over 1000 proteins, which underlies molecular computation in the brain (Collins et al., 2006). We have previously isolated and analysed proteomics datasets from molecular sub-complexes of the mammalian PSD. The two most recent approaches yielded the NMDA receptor complex or MAGUK-associated signalling complex (NRC/MASC) (Husi et al., 2000; Collins et al., 2006; Pocklington et al., 2006) and the PSD-95 complex (Fernandez et al., 2009). Our previous comparative proteomics and interactomics approaches (Emes et al., 2008; Zografos et al., 2009) showed that most types of PSD proteins were present in the early Metazoan synapse and that the changes in signalling complexity, resulting from gene family duplication and diversification, were predominantly added on specific structural modules of the protein interaction network (PIN). However, wanting to elucidate the lineage specific differences or similarities in the organization of PSD complexes, we decided to directly compare complexes of the mouse (mPSD) and fruit fly's (D. melanogaster) PSD (fPSD). In this poster we will present the results of the first fPSD purification using tagged protein trap lines (Ryder et al., 2007) as well as a comparison with the mPSD by applying a comparative interactomics workflow that uses network motifs (Milo et al., 2002) and graphlets (Przulj, 2006), in combination with molecular function and biological process annotation, to compare protein interaction networks and convergence or divergence in the organisation of different molecular families within the network's topology.
General Information
Organisations: Institute for Adaptive and Neural Computation .
Authors: Zografos, Lysimachos A., Pocklington, Andrew, Grant, Seth G. N. & Armstrong, Douglas.
Publication Date: 2010
Publication Information
Category: Poster
Original Language: English
2009
  Targeted tandem affinity purification of PSD-95 recovers core postsynaptic complexes and schizophrenia susceptibility proteins
Fernandez, E, Collins, MO, Uren, RT, Kopanitsa, MV, Komiyama, NH, Croning, MDR, Zografos, L, Armstrong, JD, Choudhary, JS & Grant, SGN 2009, 'Targeted tandem affinity purification of PSD-95 recovers core postsynaptic complexes and schizophrenia susceptibility proteins' Molecular Systems Biology, vol 5, 269, pp. -. DOI: 10.1038/msb.2009.27

The molecular complexity of mammalian proteomes demands new methods for mapping the organization of multiprotein complexes. Here, we combine mouse genetics and proteomics to characterize synapse protein complexes and interaction networks. New tandem affinity purification (TAP) tags were fused to the carboxyl terminus of PSD-95 using gene targeting in mice. Homozygous mice showed no detectable abnormalities in PSD-95 expression, subcellular localization or synaptic electrophysiological function. Analysis of multiprotein complexes purified under native conditions by mass spectrometry defined known and new interactors: 118 proteins comprising crucial functional components of synapses, including glutamate receptors, K+ channels, scaffolding and signaling proteins, were recovered. Network clustering of protein interactions generated five connected clusters, with two clusters containing all the major ionotropic glutamate receptors and one cluster with voltage-dependent K+ channels. Annotation of clusters with human disease associations revealed that multiple disorders map to the network, with a significant correlation of schizophrenia within the glutamate receptor clusters. This targeted TAP tagging strategy is generally applicable to mammalian proteomics and systems biology approaches to disease. Molecular Systems Biology 5: 269; published online 19 May 2009; doi:10.1038/msb.2009.27


General Information
Organisations: Centre for Clinical Brain Sciences.
Authors: Fernandez, Esperanza, Collins, Mark O., Uren, Rachel T., Kopanitsa, Maksym V., Komiyama, Noboru H., Croning, Mike D. R., Zografos, Lysimachos, Armstrong, J. Douglas, Choudhary, Jyoti S. & Grant, Seth G. N..
Keywords: (, , . )
Number of pages: 17
Pages: -
Publication Date: May 2009
Publication Information
Category: Article
Journal: Molecular Systems Biology
Volume: 5
ISSN: 1744-4292
Original Language: English
DOIs: 10.1038/msb.2009.27
2008
  Towards an Automated Workflow for Postsynaptic Proteome Protein-Protein Interaction Network Building.
Zografos, LA, Pocklington, A, Croning, M, Grant, SGN & Armstrong, DJ 2008, 'Towards an Automated Workflow for Postsynaptic Proteome Protein-Protein Interaction Network Building.'.
Proteomic analysis of the post synaptic density (PSD) reveals a complexity amongst the highest of any sub-cellular organelle. The PSD is a multi-protein complex consisting of over 1000 proteins which subsequently underlies the molecular computation in the brain [1]. Using protein-protein interaction (PPI) networks as a scaffold, we constructed a network model. This model reveals how the complexity of the PSP facilitates cognitive processes. Moreover the model highlights how failures in pathways may lead to cognitive illness in humans or behavioural phenotypes in animal models [2]. One can utilize models of protein interactions of the synapse proteome like the the ones created by the proposed workflow to understand cognitive function in its lowest level, that of molecular machinery, based on the interpretation, analysis and predictive value of these models.
General Information
Organisations: Institute for Adaptive and Neural Computation .
Authors: Zografos, Lysimachos A., Pocklington, Andrew, Croning, Mike, Grant, Seth G. N. & Armstrong, Douglas J..
Publication Date: 2008
Publication Information
Category: Poster
Original Language: English

Research press coverage:
Edinburgh spin-out raises £75,000 on crowdfunding platform as it seeks to find cure for Parkinson’s disease
10/03/2015

Projects:
The Molecular Machinery of Cognition: From Data to Complete Models (PhD)