Professor Russell Grant Snell

1993, Doctor of Philosophy, University of Cardiff, Genetics. 1986, Master of Science (Dist), University of Otago, Medical Physics. 1984, Bachelor of Science, University of Otago, Physics.

Research | Current

The Neurogenetics Group Our group aims to unravel the molecular mechanisms of simple and complex neurodegenerative disorders. Utilizing knowledge of causal genes and their pathways, we are developing model systems with which to investigate the molecular pathogenesis of these disorders and ultimately to screen for and test potential therapeutic agents. In particular we are working on Huntington's disease, Alzheimer's disease, Spinocerebellar ataxia and neurodevelopmental disorders such as Autism. Our approach is the application of knowledge from previous discoveries of genetically simple disorders such as Huntington's disease to inform our research into the more complex diseases such as Alzheimer's. Our studies include genetic candidate gene screens looking for statistical association with DNA variation and disease in large human cohorts generously provided by our collaborators (listed under collaborators). In addition we utilise an array of molecular methodology to dissect disease mechanisms including tissue culture, proteomics, human tissue analysis, metabolomics, RNAseq and animal models. We are currently developing a nematode worm model (C. elegans) of Alzheimer’s disease. Our hope is that this may give us insight into the disease mechanisms and assist in the identification of targets for therapeutic intervention. We are also moving into the analysis of exome and whole genome sequence with focus on neurodegenerative disease of unknown cause, and Autism; a complex multifunctional disease. Major projects Huntington’s Disease Sheep Model Huntington's disease (HD) is an inherited autosomal dominant neurodegenerative disorder caused by an expansion of a CAG trinucleotide repeat in the huntingtin (HTT) gene [Huntington's Disease Collaborative Research Group (1993). Despite identification of the gene in 1993, the underlying life-long disease process and effective treatments to prevent or delay it remain elusive. In an effort to fast-track treatment strategies for HD into clinical trials, we have developed a new large-animal HD transgenic ovine model. Sheep (Ovis aries L.), were selected because the developmental pattern of the ovine basal ganglia and cortex (the regions primarily affected in HD) is similar to the analogous regions of the human brain. Microinjection of a full-length human HTT cDNA containing 73 polyglutamine repeats under the control of the human promotor resulted in six transgenic founders varying in copy number of the transgene (Jacobsen, et al., 2010). Our current focus is on a single transgenic sheep line and we are undertaking a longitudinal study following the progression of the disease. Our aim is to use this model to identify or confirm the disease molecular mechanisms prior to the onset of symptoms. We also plan to use this model for therapeutic testing. C. elegans Model System C. elegans is a simple multicellular organism with a 3 ½ day life cycle. The genome is complete and the lineage of all cells is understood, making it an ideal model for a wide range of biological questions. It is very simple to knock the expression of genes down by feeding E.coli expressing targeted RNA molecules. It is also relatively straight forward to make transgenic animals. We are using C.elegans to model Huntington’s disease and Alzheimer’s disease. Mechanisms of Alzheimer’s disease Simple inherited mutations resulting in early onset Alzheimer’s disease (AD) have implicated directly the amyloid precursor protein (APP) and small cleavage fragments of this protein (the Amyloid Beta peptide) in AD. The peptides are found in late onset AD forming plaques, one of the characteristic features of the disease. We are developing a model of the production of the Amyloid Beta peptides in C. elegans expressing the full length APP protein and the enzyme required for cleavage. We will use this to follow the progression of cell damage and hope to use this to follow the progression of cell damage and hope to use it to test modifying agents. Dairy industry gene and mutation identification We work closely with Livestock Improvement Corporation (LIC) and the Dairy Goat Co-operative, both Hamilton based companies. Our aim is to contribute to animal selection methodology including the discovery of causative variations. Current funding MBIE Brain Research New Zealand Neurological Foundation Sunset Trust CHDI (Cure Huntington's Disease Initiative) Health Research Council New Zealand AMRF Doctoral Scholarship (Auckland Medical Research Foundation) New Zealand collaborators Professor Richard Faull and Dr Henry Waldvogel, University of Auckland - Sheep Model for Huntington’s disease Professor Mike Dragunow, University of Auckland - Neurodegeneration Dr Richard Roxburgh - Neurogenetic disease Dr Rosamund Hill – Autism Dr Phil Wood, ADHB - Alzheimer’s disease International collaborations Dr Warwick Grant, La Trobe University - C. elegans models Professors Mike Owen and Julie Williams Department of Psychological Medicine Cardiff University - The Genetics of Alzheimer’s Disease Professors James Gusella and Marcy MacDonald, Department of Genetics Harvard Medical School - Huntington’s disease genetics and a Huntington’s disease sheep model Professor Mark Rees Swansea University - Sheep Model for Huntington’s Disease Dr Simon Bawden and Skye Rudiger, South Australia - HD Transgenic Sheep Model Professor Jenny Marton, University of Cambridge - HD Transgenic Sheep Model Staff Post Doctoral Scientists Suzanne Reid Kristen Henty Jessie Jacobsen Renne Handley Kien Ly Co-locating Scientist- Livestock Improvement Corporation (LIC) Dr Matt Littlejohn

Teaching | Current

BIOSCI 351, BIOSCI 755

Postgraduate supervision

Current postgraduate students

PhD

Brendan Swan (Primary supervisor)    

Tania Law (LIC Primary supervisor Matt Littlejohn)      

Thomas Lopdell (LIC Primary supervisor Matt Littlejohn)          

Zac Maclain (AgResearch co-supervision Primary supervisor Bjorn Oback)                  

Whitney Whitford (Primary supervisor Jessie Jacobsen, co supervisors Klaus Lehnert Russell Snell) 

Emily    Mears (Primary supervisor)

Yamila Torres (co-supervisor) 

 

MSc

Cara McMurray (DairyNZ industry supervision)

Kelsey Burburough (LIC Primary supervisor Matt Littlejohn)

Shani Lawrence (co supervisor Kien Ly)

Victoria Hawkins (co supervisor Kristen Henty)

Areas of expertise

Biomedicine, molecular biology and genetics.

Committees/Professional groups/Services

Leader of the Biomedical and Applied research group at the School of Biological Sciences

Co-founder of National Autism Research Network: Minds for Minds

A Principle investigator of the Brain Research NZ CoRE fund

Founding Director, Joint Graduate School in Dairy Research and Innovation

 

Selected publications and creative works (Research Outputs)

  • Subarmaniam, N. S., Bawden, C. S., Rudiger, S. R., Yazbeck, R., Faull, R. L. M., Snell, R. G., & Howarth, G. S. (2019). Development of a novel C-13-labelled methionine breath test protocol for potential assessment of hepatic mitochondrial function in sheep using isotope-ratio mass spectrometry. INTERNATIONAL JOURNAL OF MASS SPECTROMETRY, 442, 102-108. 10.1016/j.ijms.2019.05.011
    Other University of Auckland co-authors: Richard Faull
  • Ly, K., Walker, C., Berry, S., Snell, R., Marks, E., Thayer, Z., ... Morton, S. (2019). Telomere length in early childhood is associated with sex and ethnicity. Scientific reports, 9 (1)10.1038/s41598-019-46338-x
    Other University of Auckland co-authors: Caroline Walker, Emma Marks, Susan Morton
  • Patassini, S., Begley, P., Xu, J., Church, S. J., Kureishy, N., Reid, S. J., ... Unwin, R. D. (2019). Cerebral Vitamin B5 (D-Pantothenic Acid) Deficiency as a Potential Cause of Metabolic Perturbation and Neurodegeneration in Huntington's Disease. Metabolites, 9 (6).10.3390/metabo9060113
    Other University of Auckland co-authors: Richard Faull, Suzanne Reid, Henry Waldvogel
  • Whitford, W., Lehnert, K., Snell, R. G., & Jacobsen, J. C. (2019). Evaluation of the performance of copy number variant prediction tools for the detection of deletions from whole genome sequencing data. Journal of biomedical informatics, 9410.1016/j.jbi.2019.103174
    Other University of Auckland co-authors: Whitney Whitford, Klaus Lehnert, Jessie Jacobsen
  • Cleuren, Y. T., Ewe, C. K., Chipman, K., Mears, E., Wood, C., Al-Alami, C. A. E., ... Snell, R. (2019). Extensive intraspecies cryptic variation in an ancient embryonic gene regulatory network. 10.1101/628495
    Other University of Auckland co-authors: Emily Mears
  • Murray, S. J., Black, B. L., Reid, S. J., Rudiger, S. R., Simon Bawden, C., Snell, R. G., ... Faull, R. L. M. (2019). Chemical neuroanatomy of the substantia nigra in the ovine brain. Journal of chemical neuroanatomy, 97, 43-56. 10.1016/j.jchemneu.2019.01.007
    Other University of Auckland co-authors: Suzanne Reid, Henry Waldvogel, Richard Faull
  • Lopdell, T. J., Hawkins, V., Couldrey, C., Tiplady, K., Davis, S. R., Harris, B. L., ... Littlejohn, M. D. (2019). Widespread cis-regulation of RNA editing in a large mammal. RNA (New York, N.Y.), 25 (3), 319-335. 10.1261/rna.066902.118
    URL: http://hdl.handle.net/2292/47154
  • Lopdell, T. J., Tiplady, K., Couldrey, C., Johnson, T. J. J., Keehan, M., Davis, S. R., ... Littlejohn, M. D. (2019). Multiple QTL underlie milk phenotypes at the CSF2RB locus. Genetics, selection, evolution : GSE, 51 (1)10.1186/s12711-019-0446-x

Identifiers

Contact details

Primary office location

THOMAS BUILDING EXTENSION - Bldg 110N
Level 2, Room 2016
3A SYMONDS ST
NZL
AUCKLAND 1010
New Zealand

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