Dr Michael Lardelli

Research Interests

Modelling molecular pathological events of Alzheimer's disease in zebrafish embryos

Our laboratory is currently involved in a number of projects investigating molecular pathological events associated with Alzheimer's disease. Our main focus is on the function of the presenilin genes (PSEN1 and PSEN2) that are the major loci for mutations causing Familial Alzheimer's Disease (FAD). Over 160 mutations causing FAD are known in the human PSEN1 gene and nearly all are mis-sense mutations that alter the protein coding sequence rather than non-sense mutations that truncate the protein. This led to the belief that truncated presenilin proteins have no function (i.e. they do not produce the dominant phenotype seen in FAD pedigrees). However, the unique characteristics of the zebrafish embryo model allowed us to discover that this is, in fact, not true. Instead, particular truncations of the presenilin proteins can be potently dominant negative in action. Using our unique assay for zebrafish psen2 activity (see below) we also discovered, surprisingly, that truncated PSEN1 proteins can inhibit the activity of PSEN2. We have now published this work (see Nornes et al. 2008). We believe our discovery may have implications for understanding the cause(s) of the sporadic (non-inherited) form of Alzheimer's disease that constitutes 95% of all Alzheimer's disease cases.

In other work we have discovered that, unlike in mice, the zebrafish PSEN2 orthologue, psen2, has essential developmental roles. In particular, changes in the activity of psen2, but not psen1, affect the development of a particular type of neuron in the developing spinal cord. This has given us a unique bioassay for psen2 activity. Our work is also shedding light on the central role of the presenilins in normal cell function and in cancer.

The Lardelli laboratory collaborates with a number of other laboratories in Adelaide to assist them with using zebrafish to further their reseach goals.

Publications

Scientific Publications (since 2000)

1. 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.
2. 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.
3. 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.
4. 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.
5. 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.
6. Tucker, B. and Lardelli, M. (2007) A Rapid Apoptosis Assay Measuring Relative Acridine Orange Fluorescence in Zebrafish Embryos. Zebrafish 4: 113-116.
7. 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.
8. 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.
9. 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.
10. 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.
11. 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.
12. Lardelli, M. (2003) The evolutionary relationships of zebrafish genes tbx6, tbx16/spadetail and mga. Dev. Genes Evol. 213: 519-522.
13. 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.
14. 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.
15. 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.
16. Lardelli, M. (2003) Something fishy in 21st century genomics. Today’s Life Science 15: 20-23.
17. 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.
18. Groth, C. and Lardelli, M. (2002) The structure and function of vertebrate fibroblast growth factor receptor 1. Int. J. Dev. Biol. 46: 393-400.
19. 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
20. 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.
21. 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.
22. 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.
23. 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.
24. Kortschak, R. D., Tamme, R. and Lardelli, M. (2001) Evolutionary analysis of vertebrate Notch genes. Dev. Genes Evol. 211: 350-354.
25. Camp, E. and Lardelli, M. (2001) Tyrosinase gene expression in zebrafish embryos. Dev. Genes Evol. 211: 150-153.
26. 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.
27. 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)
www.the-funneled-web.com
 
Decline in World Oil and Gas Production
(ABC Radio National Perspective16 August 2004)
http://www.abc.net.au/rn/talks/perspective/stories/s1178256.htm
 
As The Well Runs Dry
(Article in The Adelaide Review, 12 November 2004)
http://tinyurl.com/5yg9o
 
The Devil’s Handmaiden To Global Warming
(Op-Ed, 31 March 2005)
www.the-funneled-web.com
 
Thinking Ahead Of The Curve On Oil Depletion – The View From Hubbert’s Peak
(ABC Radio National Perspective 2 May 2005)
http://www.abc.net.au/rn/talks/perspective/stories/s1358063.htm
 
Oil Crisis Is Only Going To Get Worse
(Article in The Adelaide Review, 30 September 2005)
http://tinyurl.com/8gcm4
 
Drastic Action For A Post-Oil Age
(Article in The Adelaide Review, 14 October 2005)
http://tinyurl.com/c7rv4
 
Energy Efficiency – Saviour or Suicide?
(Letter to Green magazine, Issue 21 Summer 2006)
http://dev.greens.org.au/library/action/magazine/green21.pdf
 
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)
http://www.abc.net.au/rn/perspective/stories/2007/1881872.htm
 
Economic Growth to End Soon – Forever
(Article in Online Opinion, 3 May 2007)
http://www.onlineopinion.com.au/view.asp?article=5798
 
A Revolutionary Report on the Future of Oil
(Article in Online Opinion, 30 July 2007)
http://www.onlineopinion.com.au/view.asp?article=6168
 
Peak Oil Issue Not Going Away
(Article in The Adelaide Review, 17 August 2007)
http://tinyurl.com/2nl7j6
    See expanded version published as:
Our finite planet: planning for a decline in our oil bounty
(Article in Online Opinion, 20 August 2007)
http://www.onlineopinion.com.au/view.asp?article=6227
 
Sleepwalking over the oil peak
(Article in Online Opinion, 5 November 2007)
http://www.onlineopinion.com.au/view.asp?article=6584
 
To save the world we may have to waste it
(Article in Online Opinion, 15 February 2008)
http://www.onlineopinion.com.au/view.asp?article=6998
 
The 2020 Summit – more hallucination than clear vision
(ABC Radio National Perspective, 11 March 2008
   and Online Opinion article, 17 March 2008)
http://www.abc.net.au/rn/perspective/stories/2008/2186644.htm
 http://www.onlineopinion.com.au/view.asp?article=7128
 
Whither Peak Oil at Rudd’s 2020 Summit?
(Online Opinion Article, 10 April 2008)
http://www.onlineopinion.com.au/view.asp?article=7213
 
The 2020 Summit- Will Rudd’s children forgive him?
(Online Opinion Article, 23 April 2008)
http://www.onlineopinion.com.au/view.asp?article=7281
 
Submission to the Select Committee of the Legislative Council on the Impact of Peak Oil in South Australia
http://tinyurl.com/6o9l7h
 
One thousand and one, one thousand and two
(ABC Radio National Perspective, 26 June 2008)
http://www.abc.net.au/rn/perspective/stories/2008/2285685.htm
 
 
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.

Expertise for Media Contact

Categories	Science and technology, Sustainability
Expertise	The genetic control of embryo development; gene cloning; zebrafish as a model system for genetic studies; genetics; peak oil; consequences of, and mitigating responses to, oil depletion; 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.
Mobile	0428 119 300

Entry last updated: Wednesday, 19 Sep 2012