Associate Professor Michael Lardelli
|Org Unit||Molecular and Biomedical Science|
|Telephone||+61 8 8313 3212|
Molecular Life Sciences
Modelling molecular pathological events of Alzheimer's disease in zebrafish embryos
Our laboratory uses a number of techniques to analyse the functions of the PRESENILIN genes as well as other genes involved in Alzheimer's disease such as APP and SORL1. We have developed unique in vivo assays for analysis of APP protein cleavage (i.e. "gamma-secretase activity") and for measurement of autophagy. We are also using the latest genome engineering techiques to introduce human Alzheimer's disease mutations into our experimental model, the zebrafish. We then study these mutant zebrafish using "deep sequencing" analysis of gene expression to observe how the mutations change the molecular state of cells in their brains. This work involves sophisticated bioinformatic analysis of changes in gene expression.
The Lardelli laboratory collaborates with a number of other laboratories in Adelaide to assist them with using zebrafish to further their reseach goals.
Scientific Publications (since 2000)
Moussavi Nik, S.H., Morgan Newman, M., Swamynathan Ganesan, S., Chen, M., Martins, R.N., Verdile, G. and Lardelli, M. (2014) Hypoxia alters expression of Zebrafish Microtubule-associated protein Tau (mapta, maptb) gene transcripts. BMC Research Notes 7:767.
Klaric, T., Lardelli, M., Key, B., Koblar, S. and Lewis, M. Activity-dependent expression of neuronal PAS domain-containing 1 protein 4 (npas4a) in the developing zebrafish brain. Frontiers in Neuroanatomy (Accepted 18 November 2014).
Ganesan, S., Moussavi Nik, S.H., Newman, M. and Lardelli, M. (2014) Identification and expression analysis of the zebrafish orthologues of the mammalian MAP1LC3 gene family. Experimental Cell Research 328: 228-37.
Newman, M., Ebrahimie, E. and Lardelli, M. (2014) Using the zebrafish model for Alzheimer's disease research. Frontiers in Genetics, Genetics of Aging 5: Article 189.
Moussavi Nik, S.H., Croft, K., Mori, T.A. and Lardelli, M. (2014) The comparison of methods for measuring oxidative stress in zebrafish brains. Zebrafish 11: 248-54.
Newman, M., Wilson, L., Verdile, G., Lim, A., Khan, I., Moussavi Nik, S.H., Pursglove, S., Chapman, G., Martins, R.N. and Lardelli, M. (2014) Differential, dominant activation and inhibition of Notch signalling and APP cleavage by truncations of PSEN1 in human disease. Human Molecular Genetics 23: 602-17.
Wilson, L. and Lardelli, M. (2013) The development of an in vivo gamma-secretase assay using zebrafish embryos. Journal of Alzheimer's Disease 36: 521-34.
Sharman, M., Moussavi Nik, S.H., Chen, M., Ong, D., Wijaya, L., Laws, S., Taddei, K., Newman, M., Lardelli, M., Martins, R.N. and Verdile, G. (2013) The guinea pig as a model for sporadic Alzheimer's disease (AD): the impact of cholesterol intake on expression of AD-related genes. PLoS One 8: e66235.
Chen, M., Kretzschmar, D., Verdile, G. and Lardelli, M. (2013) Models of Alzheimer's Disease in Animal Models for the Study of Human Disease, edited by Michael Conn, Elsevier, Amsterdam.
Newman, M., Nornes, S., Martins, R. and Lardelli, M. (2012) Robust homeostasis of Presenilin1 protein levels by transcript regulation. Neuroscience Letters 519: 14-19.
Moussavi Nik, S. H., Wilson, L., Newman, M., Croft, K., Mori, T., Musgrave, I. and Lardelli, M. (2012) The BACE1-PSEN-AbetaPP regulatory axis has an ancient role in response to low oxygen/oxidative stress. Journal of Alzheimer's Disease 28: 515-30.
Sugano, Y. and Lardelli, M. (2011) Identification and expression analysis of the zebrafish orthologue of Klotho. Development, Genes and Evolution. 221:179-86.
Wells, S., Nornes, S. and Lardelli, M. (2011) Transgenic zebrafish recapitulating tbx16 gene early developmental expression. PLoS One 6(6):e21559.
Moussavi Nik, S., Newman, M. and Lardelli, M. (2011) The response of HMGA1 to changes in oxygen availability is evolutionarily conserved. Experimental Cell Research 317:1503-12.
Newman, M., Verdile, G., Martins, R. N. and Lardelli, M. (2011) Zebrafish as a tool in Alzheimer's disease research. Biochim Biophys Acta. - Molecular Basis of Disease 1812: 346-352.
Newman, M. and Lardelli, M. (2011) A hyperactive sleeping beauty transposase enhances transgenesis in zebrafish embryos. BMC Research Notes 3:282 doi:10.1186/1756-0500-3-282
Wells, S., Conran, J.G., Tamme, R., Gaudin, A., Webb, J. and Lardelli, M. (2011) Cryptic organisation within an apparently irregular rostrocaudal distribution of interneurons in the embryonic zebrafish. Experimental Cell Research 316: 3292-3303.
Newman, M., Wilson, L., Camp, E., Verdile, G., Martins, R. and Lardelli, M. (2010) A zebrafish melanophore model of amyloidbeta toxicity. Zebrafish 7: 155-159.
Nornes, S., Tucker, B. and Lardelli, M. (2009) Zebrafish aplnra functions in epiboly. BMC Research Notes 2:231 doi:10.1186/1756-0500-2-231.
Henshall. T. L., Tucker, B., Lumsden, A. L., Nornes, S., Lardelli, M. and Robert I. Richards (2009) Selective neuronal requirement for Huntingtin in the developing zebrafish. Human Molecular Genetics 18: 4830-42.
Nornes, S., Newman, M., Wells, S., Verdile, G., Martins, R. N. and Lardelli, M. (2009) Independent and cooperative action of Psen2 with Psen1 in zebrafish embryos. Experimental Cell Research 315: 2791-2801.
Chen, M., Martins, R. N. and Lardelli, M. (2009) Complex splicing and neural expression of duplicated tau genes in zebrafish embryos. Journal of Alzheimer's Disease 18: 305-317.
Newman, M., Tucker, B., Nornes, S., Ward, A. and Lardelli, M. (2009) Altering presenilin gene activity in zebrafish embryos causes changes in expression of genes with potential involvement in Alzheimer's Disease pathogenesis. Journal of Alzheimer's Disease 16: 133-147.
Lardelli, M. (2008) Using zebrafish in human disease research: some advantages, disadvantages and ethical considerations. Pp. 23-28 in: Proceedings of 2008 ANZCCART Conference, Auckland, New Zealand. (http://www.royalsociety.org.nz/includes/download.aspx?ID=101782)
Nornes, S., Newman, M., Verdile, G., Wells, S., Stoick-Cooper, C., Tucker, B., Frederich-Sleptsova, I., Martins, R., Lardelli, M. (2008) Interference with splicing of Presenilin transcripts has potent dominant negative effects on Presenilin activity. Human Molecular Genetics 17: 402-412. Advance access published 2 November 2007.
Wyatt, L., Wadham, C., Crocker, L.A., Lardelli, M. and Khew-Goodall, Y. (2007) The protein tyrosine phosphatise Pez regulates TGFbeta, epithelial-mesenchymal transition, and organ development. The Journal of Cell Biology 178: 1223-35.
Lumsden, A.L., Henshall, T.L., Dayan, S., Lardelli, M.T. and Richards R.I. (2007) Huntingtin-deficient zebrafish exhibit defects in iron utilization and development. Human Molecular Genetics 16: 1905-20.
Newman, M., Musgrave, I. and Lardelli, M. (2007) Alzheimer Disease: Amyloidogenesis, The Presenilins and Animal Models. Biochim Biophys Acta. - Molecular Basis of Disease 1772: 285-97.
Tucker, B. and Lardelli, M. (2007) A Rapid Apoptosis Assay Measuring Relative Acridine Orange Fluorescence in Zebrafish Embryos. Zebrafish 4: 113-116.
Khut, P-Y., Tucker, B., Lardelli, M. and Wood, S.A. (2007) Evolutionary and Expression Analysis of the Zebrafish Deubiquitylating Enzyme, Usp9. Zebrafish 4: 95-101.
Tucker, B., Hepperle, C., Kortschak, D., Rainbird, B., Wells, S., Oates, A.C. and Lardelli, M. (2007) Zebrafish Angiotensin II Receptor-like 1a (agtrl1a) is expressed in migrating hypoblast, vasculature, and in multiple embryonic epithelia. Gene Expr. Patterns 7:258-265.
Tucker, B., Richards, R. and Lardelli, M. (2006) Contribution of mGluR and Fmr1 Functional Pathways to Neurite Morphogenesis, Craniofacial Development and Fragile X Syndrome. Human Molecular Genetics 15: 3446-3458.
Tucker, B., Richards, R. and Lardelli, M. (2004) Expression of three zebrafish orthologs of human FMR1-related genes and their phylogenetic relationships. Dev. Genes Evol. 214: 567-574.
Steffen Scholpp, S., Casper Groth, C., Claudia Lohs, C., Lardelli, M. and Brand, M. (2004) Zebrafish fgfr1 is a member of the fgf8 synexpression group and is required for fgf8 signalling at the midbrain-hindbrain boundary. Dev. Genes Evol. 214:285-295.
Lardelli, M. (2003) The evolutionary relationships of zebrafish genes tbx6, tbx16/spadetail and mga. Dev. Genes Evol. 213: 519-522.
Nornes, S., Groth, C., Camp, E., Ey, P. and Lardelli, M. (2003) Developmental control of Presenilin1 expression, endoproteolysis and interaction in zebrafish embryos. Exp. Cell Res. 289:124-132.
Camp, E., Badhwar, P., Mann, G. and Lardelli, M. (2003) Expression analysis of a tyrosinase promoter sequence in zebrafish. Pigment Cell Res. 16: 117–126.
Camp, E., Hope, R., Korschak, R.D., Cox, T. and Lardelli, M. (2003) Expression of three spalt homologues in zebrafish embryos. Dev. Genes Evol. 213: 35–43.
Lardelli, M. (2003) Something fishy in 21st century genomics. Today’s Life Science 15: 20-23.
Groth, C., Nornes, S., McCarty, R., Tamme, R. and Lardelli, M. (2002) Identification of a second presenilin gene in zebrafish with similarity to the human Alzheimer’s disease gene presenilin2. Dev. Genes Evol. 212: 486-90.
Groth, C. and Lardelli, M. (2002) The structure and function of vertebrate fibroblast growth factor receptor 1. Int. J. Dev. Biol. 46: 393-400.
Tamme, R., Wells, S., Conran, J.G. and Lardelli, M. (2002) The identity and distribution of neural cells expressing the mesodermal determinant spadetail. BMC Developmental Biology 2: 9
Lardelli, M. (2002) Nonspecific, nested suppression PCR method for isolation of unknown flanking DNA (“Cold-start method”). in Methods in Molecular Biology, Vol. 192: PCR Cloning Protocols, 2nd. Ed., pages 285-99, Edited by B.-Y. Chen and H. W. Janes, Humana Press Inc., Totowa, N.J., U.S.A.
Lardelli, M. (2002) Generation and PCR-screening of bacteriophage lambda sublibraries enriched for rare clones (the "sublibrary method"). in Methods in Molecular Biology, Vol. 192: PCR Cloning Protocols, 2nd. Ed., pages 391-9, Edited by B.-Y. Chen and H. W. Janes, Humana Press Inc., Totowa, N.J., U.S.A.
Jönsson, J.-I., Xiang, Z., Pettersson, M., Lardelli, M. and Nilsson, G. (2001) Distinct and regulated expression of Notch receptors in hematopoietic lineages and during myeloid differentiation. Eur J Immunol. 31: 3240-7.
Tamme, R., Mills, K, Rainbird, B., Nornes, S. and Lardelli, M. (2001) Simple, directional cDNA cloning for in situ transcript hybridisation screens. BioTechniques 31: 938-946.
Kortschak, R. D., Tamme, R. and Lardelli, M. (2001) Evolutionary analysis of vertebrate Notch genes. Dev. Genes Evol. 211: 350-354.
Camp, E. and Lardelli, M. (2001) Tyrosinase gene expression in zebrafish embryos. Dev. Genes Evol. 211: 150-153.
Holland, L.Z., Abi Rached, Tamme, R., L., Holland, N.D., Kortschak, R.D., Inoko, H., Shiina, T., Burgtorf, C. and Lardelli, M. (2001) Characterization and developmental expression of the amphioxus homolog of Notch (AmphiNotch): Evolutionary conservation of multiple expression domains in amphioxus and vertebrates. Dev. Biol. 232:493-507.
Tamme, R., Camp, E., Kortschak, R.D. and Lardelli, M. (2000) Non-specific, nested suppression PCR method for isolation of unknown flanking DNA. BioTechniques 28: 895-902.
Popular Media and Other Presentations/Publications
Does an Approaching Peak of Oil and Gas Production Presage a National Emergency? (Viewpoint, 30 April 2004)
Decline in World Oil and Gas Production
(ABC Radio National Perspective16 August 2004)
As The Well Runs Dry
(Article in The Adelaide Review, 12 November 2004)
The Devil’s Handmaiden To Global Warming
(Op-Ed, 31 March 2005)
Thinking Ahead Of The Curve On Oil Depletion – The View From Hubbert’s Peak
(ABC Radio National Perspective 2 May 2005)
Oil Crisis Is Only Going To Get Worse
(Article in The Adelaide Review, 30 September 2005)
Drastic Action For A Post-Oil Age
(Article in The Adelaide Review, 14 October 2005)
Energy Efficiency – Saviour or Suicide?
(Letter to Green magazine, Issue 21 Summer 2006)
Scientists Need to Confront Economists About Peak Oil
(Correspondence in Nature 15 March 2007)
Peak Oil is now?
(ABC Radio National Perspective 30 March 2007)
Economic Growth to End Soon – Forever
(Article in Online Opinion, 3 May 2007)
A Revolutionary Report on the Future of Oil
(Article in Online Opinion, 30 July 2007)
Peak Oil Issue Not Going Away
(Article in The Adelaide Review, 17 August 2007)
See expanded version published as:
Our finite planet: planning for a decline in our oil bounty
(Article in Online Opinion, 20 August 2007)
Sleepwalking over the oil peak
(Article in Online Opinion, 5 November 2007)
To save the world we may have to waste it
(Article in Online Opinion, 15 February 2008)
The 2020 Summit – more hallucination than clear vision
(ABC Radio National Perspective, 11 March 2008
and Online Opinion article, 17 March 2008)
Whither Peak Oil at Rudd’s 2020 Summit?
(Online Opinion Article, 10 April 2008)
The 2020 Summit- Will Rudd’s children forgive him?
(Online Opinion Article, 23 April 2008)
Submission to the Select Committee of the Legislative Council on the Impact of Peak Oil in South Australia
One thousand and one, one thousand and two
(ABC Radio National Perspective, 26 June 2008)
Also, numerous seminars delivered including four for the SA Department of Trade and Economic Development, twice interviewed by Radio Adelaide, Twice by JJJ, Once by 3D radio.
Categories Environment, Science & Technology Expertise Alzheimer's disease; zebrafish as a model system for genetic studies; genetics; peak oil; energy; population Notes Deputy member of South Australia's Radiation Protection Committee. Has lectured on peak oil in the Australian School of Petroleum. English translator for the blog of Prof. Kjell Aleklett who is President of the Association for the Study of Peak Oil and Gas. Translator of Aleklett's book 'Peeking at Peak Oil' released in June 2012. Committee member of Sustainable Population Australia Mobile 0428 119 300
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Entry last updated: Sunday, 15 Sep 2019
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