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CELL DEATH GRADUATE COURSE
 
January 26 - 30
Doctoral Programme in Experimental Biology and Biomedicine

Center for Neuroscience and Cell Biology (CNC) - University of Coimbra

Course sponsor: Biogen Idec

Coordinator: Armanda Emanuela Santos (aesantos@ci.uc.pt)
LECTURERS:

Jonathan Ham
Molecular Haematology and Cancer Biology Unit,
Camelia Botnar Laboratories
Institute of Child Health
University College London
London WC1N 1EH, UK
 
Michael J. Courtney
Dept. of Neurobiology
A. I. Virtanen Institute
University of Kuopio
Kuopio FIN 70211, Finland
 
Luis Miguel Martins
Cell Death Regulation Laboratory
MRC Toxicology Unit
Leicester LE1 9HN, UK
 
 
Armanda E. Santos
Center for Neuroscience and Cell Biology &
Faculty of Pharmacy
University of Coimbra
3004-517 Coimbra, Portugal
 
 
COURSE SCHEDULE
 
Monday, January 26
 
9:45 – 11:00 Introduction to apoptosis
Jonathan Ham
 
11:15 – 12:30 Introduction to mitochondria
Luís Miguel Martins
 
14:30 – 15:45 Mitochondria and cell death
Luís Miguel Martins
 
 
Tuesday, January 27
 
9:45 – 11:00 Regulation of the cell death programme by signalling pathways
Jonathan Ham
 
11:15 – 12:30 Stress-activated protein kinases in cell death
Michael Courtney
 
14:30 – 16:00 Analysis and discussion of papers
Jonathan Ham
 
Note: Student presentations should not take more than 30 minutes per paper
 
“Bax activation is initiated at a novel interaction site”
Gavathiotis et al., 2008, Nature 455: 1076-81
Students presenting the paper: Ana Lúcia Ramos, Marco Filipe Craveiro
 
“An inhibitor of Bcl-2 family proteins induces regression of solid tumors”
Oltersdorf et al., 2005, Nature 435: 677-81
Students presenting the paper: Carolina Coelho, Joana Barbosa
 
 
Wednesday, January 28
 
9:45 – 11:00 The glutamatergic synapse
Michael Courtney
 
11:15 – 12:30 Mitochondrial stress pathways and cell death
Luís Miguel Martins
 
14:30 – 16:00 Analysis and discussion of papers
Luís Miguel Martins
 
Note: Student presentations should not take more than 30 minutes per paper
 
“Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery”
Datta et al., 1997, Cell 91: 231-41
Students presenting the paper: Ana Sofia Rodrigues, Diana Carvalho
 
“Induction of apoptotic program in cell-free extracts: requirement for dATP and cytochrome c”
Liu et al., 1996, Cell 86: 147-57
Students presenting the paper: Beatriz Sousa, Pedro Costa
 
“Premature ageing in mice expressing defective mitochondrial DNA polymerase”
Trifunovic et al., 2004, Nature 429: 417-23
Students presenting the paper: Samira Ferreira, Daniel Oberdoerfer
 
 
Thursday, January 29
 
9:45 – 11:00 Mechanisms of glutamate receptor mediated excitotoxic neuronal death I: Ca2+-permeable AMPA receptor-mediated excitotoxicity
Armanda Santos
 
11:15 – 12:30 Mechanisms of glutamate receptor mediated excitotoxic neuronal death II: NMDA receptors and associated proteins in excitotoxicity
Michael Courtney
 
14:30 – 16:00 Analysis and discussion of papers
Michael Courtney
 
Note: Student presentations should not take more than 30 minutes per paper
The first two papers are highly related, thus it is convenient that students take a look on both.
 
“Treatment of ischemic brain damage by perturbing NMDA receptor- PSD-95 protein interactions”
Aarts et al., 2002, Science 298: 846-850
Students presenting the paper: Renata Gomes, Joana Fernandes
 
“PDZ protein interactions underlying NMDA receptor-mediated excitotoxicity and neuroprotection by PSD-95 inhibitors”
Cui et al., 2007, J Neurosci 27: 9901-9915
Students presenting the paper: Sílvia Silva, Joana Real
 
“Multi-site phosphorylation regulates Bim stability and apoptotic activity”
Hubner et al., 2008, Mol Cell 30: 415-425
Students presenting the paper: Carlos Melo, Pedro Carvalho
 
 
Friday, January 30
 
11:15 – 12:30 Transcriptional control of apoptosis in developing neurons / seminar
Jonathan Ham
 
 
16h: CNC seminar
"Protein interactions - possible therapeutic targets for neurodegenerative diseases"
Michael J. Courtney
 
 
BACKGROUND READING
 
Yuan J, Lipinski M, and Degtterev A. (2003)
Diversity in the mechanisms of neuronal death.
Neuron 40: 401-413 (Review)
 
Danial NN & Korsmeyer SJ. (2004)
Cell death: critical control points.
Cell 116: 205-219 (Review)
 
Willis SN & Adams JM. (2005)
Life in the balance: how BH3-only proteins induce apoptosis.
Curr Opin Cell Biol. 17: 617-625 (Review)

Hengartner MO. (2000)
The biochemistry of apoptosis.
Nature 407: 770-776 (Review)
 
Whitfield, J., Neame, S.J., Paquet, L., Bernard, O. and Ham, J. (2001)
Dominant negative c-Jun promotes neuronal survival by reducing Bim expression and inhibiting mitochondrial cytochrome c release.  Neuron 29, 629-643
 
Gilley, J., Coffer, P. and Ham, J. (2003)
FOXO transcription factors directly activate bim gene expression and promote apoptosis in sympathetic neurons.
Journal of Cell Biology 162, 613-622

Ham, J., Towers, E., Gilley, J., Terzano, S. and Randall, R.A. (2005)
BH3-only proteins: key regulators of neuronal apoptosis. 
Cell Death and Differentiation 12, 1015-1020 (Review)
 
Liu SJ & Zukin RS. (2007)
Ca2+-permeable AMPA receptors in synaptic plasticity and neuronal death.
TINS 30: 126-134 (Review)
 
Kwak S & Weiss JH. (2006)
Calcium-permeable AMPA channels in neurodegenerative disease and ischemia.
Curr Op Neurobiol 16: 281-287 (Review)
 
Santos AE, Duarte CB, Iizuka M, Barsoumian EL, Ham J, Lopes MC, Carvalho AP, and Carvalho AL. (2006)
Excitotoxicity mediated by Ca2+-permeable GluR4-containing AMPA receptors involves the AP-1 transcription factor.
Cell Death Differ 13:652-60
 
Borsello T, Clarke PG, Hirt L, Vercelli A, Repici M, Schorderet DF, Bogousslavsky J, and Bonny C. (2003)
A peptide inhibitor of c-Jun N-terminal kinase protects against excitotoxicity and cerebral ischemia.
Nat Med. 9:1180-6
 
Cao J, Semenova MM, Solovyan VT, Han J, Coffey ET, and Courtney MJ. (2004)
Distinct requirements for p38alpha and c-Jun N-terminal kinase stress-activated protein kinases in different forms of apoptotic neuronal death.
J Biol Chem. 279:35903-13.
 
Wang LH, Besirli CG, and Johnson EM Jr. (2004)
Mixed-lineage kinases: a target for the prevention of neurodegeneration.
Annu Rev Pharmacol Toxicol. 44:451-74 (Review)
 
Weston CR & Davis RJ. (2007)
The JNK signal transduction pathway.
Curr Op Cell Biol 19: 142-149 (Review)
 
Cui J, Zhang M, Zhang Y and Xu Z. (2007)
The JNK pathway: diseases involved and therapeutical potential.
Acta Pharmacol Sin 28: 601-608 (Review)
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