Dr Damian Crowther
University position
Group Leader
Dr Damian Crowther is pleased to consider applications from prospective PhD students.
Departments
Department of Genetics and Department of Medicine
Institutes
Cambridge Institute for Medical Research (CIMR)
Home page
Research Themes
Interests
We are dedicated to understanding the molecular pathogenesis of neurodegenerative diseases using the fruit fly, Drosophila melanogaster, as our primary tool. Our creation of a fly model of Alzheimer's disease by expressing the amyloid beta peptide in the insect's brain has started two interlinked lines of research. The first, in collaboration with Prof. David Lomas in the Dept. of Medicine, uses the powerful genetic tools that are available in the fly to find genes that modify the brain's sensitivity to the toxic effects of the Abeta peptide. Genetic screens have revealed important pathways of disease that we are investigating using biochemical, cell culture and animal modelling approaches. The second strand, in collaboration with Prof. Chris Dobson and Dr. Michele Vendruscolo in the Dept. of Chemistry, correlates the biophysical properties of peptides with their aggregation propensity. The fly allows us to observe the generic toxicity of protein aggregates in vivo.
Research Focus
KeywordsAlzheimer's Disease dementia animal model protein aggregation genetics |
Clinical conditionsAlzheimer's disease Cognitive impairment |
Equipment
Behavioural analysis
Biophysical analysis of protein aggregation
Cell culture
Enzyme assays
FPLC/HPLC
Microscopy
Protein purification
Recombinant protein expression
Transgenic fly models of neurodegeneration
Collaborators
CambridgeMichael Ashburner David Lomas Stefan Marciniak | United KingdomSimon Lovestone Web: http://internal.iop.kcl.ac.uk/ipublic... Linda Partridge Web: http://www.ucl.ac.uk/~ucbtce... David Sattelle Web: http://www.mrcfgu.ox.ac.uk/researc... Louise Serpell Web: http://www.sussex.ac.uk/biochem... InternationalMark Wilson Web: http://www.uow.edu.au/science... |
Key publications
Rival, T, Page, R, Chandraratna, D, Sendall, TJ, Ryder, E, Liu, B, Lewis, H, Rosahl, T, Hider, R, Camargo, LM, Shearman, MS, Crowther, DC, Lomas, DA (2009), “Fenton chemistry and oxidative stress mediate the toxicity of the β-amyloid peptide in a Drosophila model of Alzheimer’s disease. ” Eur. J. Neurosci. 29: 1335-1347
Luheshi LM, Tartaglia GG, Brorsson AC, Pawar AP, Watson IE, Chiti F, Vendruscolo M, Lomas DA, Dobson CM, Crowther DC (2007), “Systematic In Vivo Analysis of the Intrinsic Determinants of Amyloid beta Pathogenicity” PLoS Biol 5(11):e290 Details
Crowther DC, Kinghorn KJ, Miranda E, Page R, Curry JA, Duthie FA, Gubb DC, Lomas DA (2005), “Intraneuronal Aβ, non-amyloid aggregates and neurodegeneration in a Drosophila model of Alzheimer's disease” Neuroscience 132:123-35 Details
Publications
in press
Nerelius, C, Sandegren, A, Sargsyan, A, Raunak, Leijonmarck, H, Chatterjee, U, Fisahn, A, Imarisio, S, Lomas, DA, Crowther, DC, Stromberg, R, Johansson, J (in press), “α-Helix-targeting reduces amyloid β-peptide toxicity. ” Proc Natl Acad Sci U S A
2008
Crowther DC, Page R, Rival T, Chandraratna DS, Lomas DA (2008), “Using a Drosophila model of Alzheimer's disease.” SEB Exp Biol Ser 60:57-77 Details
Luheshi LM, Crowther DC, Dobson CM (2008), “Protein misfolding and disease: from the test tube to the organism.” Curr Opin Chem Biol 12(1):25-31 Details
Miranda E, MacLeod I, Davies MJ, Pérez J, Römisch K, Crowther DC, Lomas DA (2008), “The intracellular accumulation of polymeric neuroserpin explains the severity of the dementia FENIB.” Hum Mol Genet 17(11):1527-39 Details
2007
Nielsen HM, Minthon L, Londos E, Blennow K, Miranda E, Perez J, Crowther DC, Lomas DA, Janciauskiene SM (2007), “Plasma and CSF serpins in Alzheimer disease and dementia with Lewy bodies.” Neurology 69(16):1569-79 Details
2006
Crowther DC, Page R, Chandraratna D, Lomas DA (2006), “A Drosophila model of Alzheimer's disease.” Methods Enzymol 412:234-55 Details
Kinghorn KJ, Crowther DC, Sharp LK, Nerelius C, Davis RL, Chang HT, Green C, Gubb DC, Johansson J, Lomas DA (2006), “Neuroserpin binds Abeta and is a neuroprotective component of amyloid plaques in Alzheimer disease.” J Biol Chem 281(39):29268-77 Details
Sharp LK, Mallya M, Kinghorn KJ, Wang Z, Crowther DC, Huntington JA, Belorgey D, Lomas DA (2006), “Sugar and alcohol molecules provide a therapeutic strategy for the serpinopathies that cause dementia and cirrhosis.” FEBS J 273(11):2540-52 Details
2005
Lomas DA, Belorgey D, Mallya M, Miranda E, Kinghorn KJ, Sharp LK, Phillips RL, Page R, Robertson AS, Crowther DC (2005), “Molecular mousetraps and the serpinopathies.” Biochem Soc Trans 33(Pt 2):321-30 Details
2004
Belorgey D, Sharp LK, Crowther DC, Onda M, Johansson J, Lomas DA (2004), “Neuroserpin Portland (Ser52Arg) is trapped as an inactive intermediate that rapidly forms polymers: implications for the epilepsy seen in the dementia FENIB.” Eur J Biochem 271(16):3360-7 Details
Crowther DC, Belorgey D, Miranda E, Kinghorn KJ, Sharp LK, Lomas DA (2004), “Practical genetics: alpha-1-antitrypsin deficiency and the serpinopathies.” Eur J Hum Genet 12(3):167-72 Details
Crowther DC, Kinghorn KJ, Page R, Lomas DA (2004), “Therapeutic targets from a Drosophila model of Alzheimer's disease.” Curr Opin Pharmacol 4(5):513-6 Details
Lomas DA, Belorgey D, Mallya M, Onda M, Kinghorn KJ, Sharp LK, Phillips RL, Page R, Crowther DC, Miranda E (2004), “Polymerisation underlies alpha1-antitrypsin deficiency, dementia and other serpinopathies.” Front Biosci 9:2873-91 Details
2003
Crowther DC, Serpell LC, Dafforn TR, Gooptu B, Lomas DA (2003), “Nucleation of alpha 1-antichymotrypsin polymerization.” Biochemistry 42(8):2355-63 Details
2002
Belorgey D, Crowther DC, Mahadeva R, Lomas DA (2002), “Mutant Neuroserpin (S49P) that causes familial encephalopathy with neuroserpin inclusion bodies is a poor proteinase inhibitor and readily forms polymers in vitro.” J Biol Chem 277(19):17367-73 Details