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)

  • Lopdell, T. J., Tiplady, K., Struchalin, M., Johnson, T. J. J., Keehan, M., Sherlock, R., ... Spelman, R. J. (2017). DNA and RNA-sequence based GWAS highlights membrane-transport genes as key modulators of milk lactose content. BMC genomics, 18 (1)10.1186/s12864-017-4320-3
    Other University of Auckland co-authors: Thomas Lopdell
  • Handley, R. R., Reid, S. J., Brauning, R., Maclean, P., Mears, E. R., Fourie, I., ... McLaughlan, C. J. (2017). Brain urea increase is an early Huntington's disease pathogenic event observed in a prodromal transgenic sheep model and HD cases. Proceedings of the National Academy of Sciences of the United States of America, 114 (52), E11293-E11302. 10.1073/pnas.1711243115
    Other University of Auckland co-authors: Renee Handley, Suzanne Reid, Garth Cooper, Henry Waldvogel, Richard Faull
  • Whitford, W., Hawkins, I., Glamuzina, E., Wilson, F., Marshall, A., Ashton, F., ... Lehnert, K. (2017). Compound heterozygous SLC19A3 mutations further refine the critical promoter region for biotin-thiamine-responsive basal ganglia disease. Cold Spring Harbor Molecular Case Studies, 3 (6)10.1101/mcs.a001909
    Other University of Auckland co-authors: Jessie Jacobsen, Klaus Lehnert, Whitney Whitford, Don Love
  • Swan, B., Jacobsen, J., Taylor, J., Hill, R., Lehnert, K., & Snell, R. (2017). IDENTIFICATION OF CANDIDATE AUTISM GENETIC VARIANTS INCLUDING A HETEROZYGOUS STOP-GAIN MUTATION IN ASXL3 THAT REFINES AUTISM SPECTRUM DISORDER DIAGNOSIS TO BAINBRIDGE-ROPERS SYNDROME. Paper presented at 23rd Annual World Congress of Psychiatric Genetics (WCPG), Toronto, CANADA. 16 October - 20 October 2015. EUROPEAN NEUROPSYCHOPHARMACOLOGY. (pp. 2).
  • Reid, S. J., Mckean, N. E., Henty, K., Portelius, E., Blennow, K., Rudiger, S. R., ... Faull, R. L. M. (2017). Alzheimer's disease markers in the aged sheep (Ovis aries). Neurobiology of Aging, 58, 112-119. 10.1016/j.neurobiolaging.2017.06.020
    URL: http://hdl.handle.net/2292/35905
    Other University of Auckland co-authors: Richard Faull, Suzanne Reid, Renee Handley, Henry Waldvogel
  • Virues-Ortega, J., Lehnert, K., Swan, B., Taylor, M. W., Southee, A., Dougan, D., ... Jacobsen, J. C. (2017). The New Zealand minds for minds autism spectrum disorder self-reported cohort. Research in Autism Spectrum Disorders, 36, 1-7. 10.1016/j.rasd.2016.12.003
    Other University of Auckland co-authors: Mike Taylor, Javier Virues-Ortega, Klaus Lehnert, Jessie Jacobsen
  • Fink, T., Tiplady, K., Lopdell, T., Johnson, T., Snell, R. G., Spelman, R. J., ... Littlejohn, M. D. (2017). Functional confirmation of PLAG1 as the candidate causative gene underlying major pleiotropic effects on body weight and milk characteristics. Scientific Reports, 710.1038/srep44793
    URL: http://hdl.handle.net/2292/33831
    Other University of Auckland co-authors: Thomas Lopdell
  • Tippett, L. J., Waldvogel, H. J., Snell, R. G., Vonsattel, J.-P., Young, A. B., & Faull, R. L. M. (2017). The complexity of clinical Huntington's disease: Developments in molecular genetics, neuropathology and neuroimaging biomarkers. In P. Beart, M. Robinson, M. Rattray, N. J. Maragakis (Eds.) Neurodegenerative diseases: Pathology, mechanisms, and potential therapeutic targets (pp. 129-161). Cham, Switzerland: Springer International Publishing. 10.1007/978-3-319-57193-5_5
    URL: http://hdl.handle.net/2292/35527
    Other University of Auckland co-authors: Richard Faull, Lynette Tippett, Henry Waldvogel