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Level 11, KGV Building
Missenden Road
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Post Office Box M30
Missenden Road NSW 2050

Phone: (02) 9515-6111
Fax: (02) 9515-9610

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Neurobiology and Molecular Medicine

Our Research

Director: Professor Garth Nicholson 
Principal Scientist: Associate Professor Marina Kennerson

The Northcott Neuroscience Laboratory, headed by Professor Garth Nicholson is internationally renowned in the field of molecular genetics of human hereditary neuropathies and motor neurone disorders. Together with Associate Professor Kennerson, the laboratory has made important contributions to the discovery of gene mutations causing neurodegeneration of peripheral nerve and motor neurons. The discovery of mutant genes in our families has uncovered new mechanisms causing disease. We are setting up ways to screen compounds for possible treatments. In hereditary sensory neuropathy we have commenced a pilot treatment trial.

Our laboratory is truly translational and focuses on determining the underlying causes of neurodegenerative disease firstly to develop diagnostic tools and eventually to develop effective treatment therapies.

Gene Discovery Program for Inherited Peripheral Neuropathies M Kennerson, M Brewer, A Cutrupi, A Drew, M Ellis, A Kidambi, C Ly, G. Nicholson

Charcot-Marie-Tooth (CMT) disease CMT is a degenerative disorder of the peripheral nerve affecting both sensory and motor nerves. Individuals who suffer from this disorder experience distal muscle weakness of legs and arms, foot deformities and sensory loss. Motor and sensory neurons are unique cells with long axons (up to 1 metre) that require continuous maintenance from the cell body to the nerve endings. The breakdown of this maintenance leads to the 'dying back' of the nerve ends (axonal degeneration). Our research aim is to identify the biological pathways leading to axonal degeneration with the ultimate goal of developing treatments. To do this we identify the faulty gene in families with CMT disease.

Identifying genes for CMT disease has entered an exciting era in which availability of next generation sequencing (NGS) is expediting the gene discovery process. Central to our research has been the analysis of the largest CMT cohort in an Australian study using whole exoming sequencing. Our 'exomes' provide sequence information on all the known genes in our DNA. Over 300 patient exomes have been analysed for the 80 genes known to cause CMT in the one test. Through our research this method of gene testing has now been developed for a clinical setting and is offered as a CMT genetic test in our diagnostic laboratory which is a national reference centre for these disorders.

This year we provided definitive linkage data mapping an axonal form of CMT on chromosome 22 in which the causative MORC2 gene localises. In collaboration with colleagues at the University of Malaya we have used a combination of linkage and whole exome sequencing to map a new locus chromosome 14 and identify a causative gene for recessive CMT.

We have used whole genome sequencing which covers gene and non-gene DNA sequence. We have shown for the first time unique disease causing DNA re-arrangements in a family with X-lined CMT (CMTX3) and a family with hereditary motor neuropathy on chromosome 7 (DHMN1). Our discoveries have highlighted the importance of looking for DNA re-arrangements (structural variation) in families where the coding exons of genes have been eliminated.

Worm models for Inherited Peripheral Neuropathies M. Brewer, A. Siddell, G. Nicholson, M. Kennerson

This year we have introduced worm technology into the laboratory as a possible fast track screen for drug therapies for degenerative disorders of nerve. Caenorhabditis elegans (C. elegans) is a small (about 1 mm in length), transparent nematode with a short life cycle and a well characterised nervous system - making them ideal for studying axonal degeneration caused by genetic mutations found in patients with inherited peripheral neuropathy (IPN).

Candidate gene mutations will be overexpressed in the worm's GABA-motor neurons - which innervate the muscles that control worm locomotion. Gene variants that are pathogenic are expected to cause axonal degeneration as evidenced by abnormal locomotive behaviour and disrupted axon structure (observed visually by the endogenous expression of green fluorescent protein in the GABAergic neurons). This project complements our current gene discovery program by providing additional in vivo evidence as to whether a candidate gene mutation is the cause of inherited peripheral neuropathy in our patients. Models established in this project will be used for downstream functional studies and therapeutic drug screens.

Cell models of Inherited Peripheral Neuropathies G Perez-Siles, M. Ellis, A. Kidambi, C. Ly, A.Siddell, G. Nicholson, M. Kennerson

Our group has a cell biology program for the study of mutations causing inherited peripheral neuropathies. Understanding the normal function and the consequences of the mutations in neuronal cell lines, will further our understanding of the mechanisms causing degenerative nerve disease.

Two genes of interest are the PDK3 and ATP7A gene mutations, previously identified by our group as causative disease mutations of two forms of hereditary neuropathy.

Using patient derived cells with the PDK3 gene mutation we have recently identified a highly potential 'drugable' target for therapeutic intervention. We have also successfully developed a knock-in mouse model that expresses a human mutation in the copper transporter ATP7A. This model faithfully recapitulates the defective cellular events observed in the human patient fibroblasts. We believe this model will facilitate identification and testing of therapeutic targets to develop effective copper based therapies for the disease.

In 2016 we have obtained funding to implement the use of induced pluripotent stem cells (iPSC) reprogrammed from patient skin cells. This exciting new technology will allow us to study the effects of gene mutations in motor neurons derived from the patient. Our focus will be to develop motor neuron models harbouring patient mutations that can be used for drug screening as well as understanding gene dysregulation caused by large DNA re-arrangements (involving hundreds of thousands to millions of bases) in some forms of hereditary neuropathy.

Key Achievements

  • We have reported structural variation (SV) mutations (large DNA insertion re-arrangements) causing gene dysregulation as a new genetic disease mechanism for Charcot-Marie-Tooth neuropathy and hereditary motor neuropathy. The study of SV mutations is an important initiative in our research to determine the contribution of pathogenic DNA re-arrangements as a cause of CMT.
  • We have reported the first knock in mouse model for X-linked distal hereditary motor neuropathy (dHMNX). The mutated Atp7a copper transporter expressed in the mouse model shows trafficking defects and reduced protein mutant protein also observed in dHMNX patients. This model will be a key resource to develop copper based therapies to prevent motor neuron degeneration.
  • Professor Nicholson was an invited speaker and A/Prof Kennerson was invited speaker and Chairperson at the 2016 Asian Oceanic Congress of Neurology, Kuala Lumpur, Malaysia.
  • A/Prof Kennerson presented new hereditary motor neuropathy structural variation mutation as a platform presentation at the 2016 65th American Society of Human Genetics, Vancouver, Canada.  
  • A/Prof Kennerson was an invited speaker and Session Chairperson at the 2016 International Conference of the Genetics Society of Korea, Jeju Island, South Korea.
  • Dr Gonzalo Perez-Siles was an invited speaker for the 2016 Biometals Symposium, Florey Institute of Neuroscience and Mental Health, Melbourne, Victoria.
  • The group has been part of an initiative to bring together researchers in neuropathy across Sydney and participated in the inaugural Sydney Neuropathy Research Group (SyNRG) which is part of the Neuroscience Network at Sydney University. Our group contributes genomics/bioinformatics expertise and excellence in gene discovery skills.
  • Professor Nicholson is on the advisory board of the Inherited Neuropathy Consortium of the USA and is medical advisor to the CMT Association of Australia and is the patron of the MJD Foundation of Australia.
  • Associate Professor Kennerson was nominated Secretariat of the Asian Oceanic Inherited Neuropathy Consortium (AOINC) established at an inaugural meeting held in Kuala Lumpur, Malaysia 2016.
  • Associate Professor Kennerson was appointed Unit of Study Co-Ordinator for the Brain and Mind Centre Post Graduate Masters by course unit “Genetics of Brain and Mind Disorders”.


  • Peripheral Nerve Society Meeting Travel Award (2016) - awarded to Dr Megan Brewer, Dr Gonzalo Perez-Siles and Dr Alexander Drew
  • Concord Repatriation General Hospital Travel Scholarship - Dr Megan Brewer
  • Concord Hospital Early Career Research Award – Dr Gonzalo Perez-Siles
  • Best Poster Award at the 2016 NSW ASMR Research Meeting – PhD student Anthony Cutrupi
  • Tony Basten Fellowship, Sydney Medical School (2016) – Dr Gonzalo Perez-Siles
  • 2015/2016 Summer Student Rebecca Webby won the Summer Student ANZAC Seminar and went on to represent the institute at the Deans’s Prize Awards.

Research Staff

  • Associate Professor Marina Kennerson PhD - Principal Research Fellow/Team Leader
  • Associate Professor Stephen Reddel MBBS, PhD - Neurologist
  • Dr Megan Brewer PhD - Postdoctoral Fellow
  • Dr Gonzalo Perez-Siles PhD - Postdoctoral Fellow
  • Dr Alexander Drew PhD - Postdoctoral Fellow
  • Carolyn Ly BMedSc (Hons) - Research Assistant
  • Aditi Kidambi BSc (Hons) - Research Assistant
  • Melina Ellis BSc (Hons) - Research Assistant
  • Priya Kumar BSc (Hons) - Research Assistant

Higher Degree Students:


  • Mr Anthony Cutrupi


  • Ms Anna Siddell

Publications and Presentations

Publication Details:
  1. Drew AP, Cutrupi AN, Brewer MH, Nicholson GA and Kennerson ML A 1.35 Mb DNA fragment in inserted into the DHMN1 locus on chromosome 7q34-q36.2. Hum. Genet. 2016 135:1269-1278.
  2. Perez-Siles G, Ly C, Grant A, Drew AP, Yiu EM, Ryan MM, Chuang DT, Tso S-C, Nicholson GA and Kennerson ML Pathogenic mechanisms underlying X-linked Charcot-Marie-Tooth Neuropathy (CMTX6) in patients with a pyruvate dehydrogenase kinase 3 mutation. Neurobiol. Dis. 2016 94:237-244.
  3. Brewer MH, Chaudhry R, Qi J, Kidambi A, Drew AP, Menezes MP, Ryan MR, Farrar MA, Mowat D, Subramanian GM, Young HK, Zuchner S, Reddel SW, Nicholson GA and Kennerson ML Whole genome sequencing identifies a 78 kb insertion from chromosome 8 as the cause of Charcot-Marie-Tooth neuropathy CMTX3. PLOS Genet. 2016 12(7):e1006177.
  4. Perez-Siles G, Grant A, Ellis M, Ly C, Kidambi A, Khalil M, Llanos RM, La Fontaine S, Strickland A, Zuchner S, Bermeo S, Neist E, Brennan-Speranza, Takata RI, Speck-Martins CE, Mercer JFB, Nicholson GA and Kennerson ML Characterising the molecular phenotype of an Atp7aT985I conditional knock in mouse model for X-linked distal hereditary motor neuropathy (dHMNX). Metallomics 2016 8(9):981-992.
  5. Kennerson ML, Kim EJ, Siddell A, Kidambi A, Kim SM, Hong YB, Hwang SH, Chung KW, Choi BO. X-linked Charcot-Marie-Tooth disease type 6 (CMTX6) patients with a p.R158H mutation in the pyruvate dehydrogenase kinase isoenzyme 3 gene. J. Periphr Nerv Syst 2016 21:45-51.
  6. Tey S, Ahmad-Annuar A, Drew AP, Shahrizaila N, Nicholson GA, Kennerson ML. Mutation analysis of genes within the dynactin complex in a cohort of hereditary peripheral neuropathies. Clin Genet. 2016 90:127-133.
  7. Albulym OM, Kennerson ML*, Harms MB, Drew AP, Siddell AH, Auer-Grumbach M, Pestronk A, Connolly A, Baloh RH, Zuchner S, Reddel SW, Nicholson GA. MORC 2 mutations cause axonal Charcot-Marie-Tooth disease with pyramidal signs.  Annals of Neurology 2016 79:419-427.  *equal first author
  8. Fifita JA, Williams KL, Sundaramoorthy V, Mccann EP, Nicholson GA, Atkin JD, Blair IP. A novel amyotrophic lateral sclerosis mutation in OPTN induces ER stress and Golgi fragmentation. Amyotroph Lateral Scler Frontotemporal Degener. 2017 18:126-133. 
  9. van Rheenen W, Shatunov A, Dekker AM, McLaughlin RL, Diekstra FP, Pulit SL, van der Spek RA, Võsa U, de Jong S, Robinson MR, Yang J, Fogh I, van Doormaal PT, Tazelaar GH, Koppers M, Blokhuis AM, Sproviero W, Jones AR, Kenna KP, van Eijk KR, Harschnitz O, Schellevis RD, Brands WJ, Medic J, Menelaou A, Vajda A, Ticozzi N, Lin K, Rogelj B, Vrabec K, Ravnik-Glava? M, Koritnik B, Zidar J, Leonardis L, Grošelj LD, Millecamps S, Salachas F, Meininger V, de Carvalho M, Pinto S, Mora JS, Rojas-García R, Polak M, Chandran S, Colville S, Swingler R, Morrison KE, Shaw PJ, Hardy J, Orrell RW, Pittman A, Sidle K, Fratta P, Malaspina A, Topp S, Petri S, Abdulla S, Drepper C, Sendtner M, Meyer T, Ophoff RA, Staats KA, Wiedau-Pazos M, Lomen-Hoerth C, Van Deerlin VM, Trojanowski JQ, Elman L, McCluskey L, Basak AN, Tunca C, Hamzeiy H, Parman Y, Meitinger T, Lichtner P, Radivojkov-Blagojevic M, Andres CR, Maurel C, Bensimon G, Landwehrmeyer B, Brice A, Payan CA, Saker-Delye S, Dürr A, Wood NW, Tittmann L, Lieb W, Franke A, Rietschel M, Cichon S, Nöthen MM, Amouyel P, Tzourio C, Dartigues JF, Uitterlinden AG, Rivadeneira F, Estrada K, Hofman A, Curtis C, Blauw HM, van der Kooi AJ, de Visser M, Goris A, Weber M, Shaw CE, Smith BN, Pansarasa O, Cereda C, Del Bo R, Comi GP, D'Alfonso S, Bertolin C, Sorarù G, Mazzini L, Pensato V, Gellera C, Tiloca C, Ratti A, Calvo A, Moglia C, Brunetti M, Arcuti S, Capozzo R, Zecca C, Lunetta C, Penco S, Riva N, Padovani A, Filosto M, Muller B, Stuit RJ; PARALS Registry; SLALOM Group; SLAP Registry; FALS Sequencing Consortium; SLAGEN Consortium; NNIPPS Study Group, Blair I, Zhang K, McCann EP, Fifita JA, Nicholson GA, Rowe DB, Pamphlett R, Kiernan MC, Grosskreutz J, Witte OW, Ringer T, Prell T, Stubendorff B, Kurth I, Hübner CA, Leigh PN, Casale F, Chio A, Beghi E, Pupillo E, Tortelli R, Logroscino G, Powell J, Ludolph AC, Weishaupt JH, Robberecht W, Van Damme P, Franke L, Pers TH, Brown RH, Glass JD, Landers JE, Hardiman O, Andersen PM, Corcia P, Vourc'h P, Silani V, Wray NR, Visscher PM, de Bakker PI, van Es MA, Pasterkamp RJ, Lewis CM, Breen G, Al-Chalabi A, van den Berg LH, Veldink JH. Genome-wide association analyses identify new risk variants and the genetic architecture of amyotrophic lateral sclerosis. Nat Genet. 2016 48(9):1043-8.
  10. Kenna KP, van Doormaal PT, Dekker AM, Ticozzi N, Kenna BJ, Diekstra FP, van Rheenen W, van Eijk KR, Jones AR, Keagle P, Shatunov A, Sproviero W, Smith BN, van Es MA, Topp SD, Kenna A, Miller JW, Fallini C, Tiloca C, McLaughlin RL, Vance C, Troakes C, Colombrita C, Mora G, Calvo A, Verde F, Al-Sarraj S, King A, Calini D, de Belleroche J, Baas F, van der Kooi AJ, de Visser M, Ten Asbroek AL, Sapp PC, McKenna-Yasek D, Polak M, Asress S, Muñoz-Blanco JL, Strom TM, Meitinger T, Morrison KE; SLAGEN Consortium, Lauria G, Williams KL, Leigh PN, Nicholson GA, Blair IP, Leblond CS, Dion PA, Rouleau GA, Pall H, Shaw PJ, Turner MR, Talbot K, Taroni F, Boylan KB, Van Blitterswijk M, Rademakers R, Esteban-Pérez J, García-Redondo A, Van Damme P, Robberecht W, Chio A, Gellera C, Drepper C, Sendtner M, Ratti A, Glass JD, Mora JS, Basak NA, Hardiman O, Ludolph AC, Andersen PM, Weishaupt JH, Brown RH Jr, Al-Chalabi A, Silani V, Shaw CE, van den Berg LH, Veldink JH, Landers JE. NEK1 variants confer susceptibility to amyotrophic lateral sclerosis. Nat Genet. 2016 48(9):1037-42.
  11. Williams KL, Topp S, Yang S, Smith B, Fifita JA, Warraich ST, Zhang KY, Farrawell N, Vance C, Hu X, Chesi A, Leblond CS, Lee A, Rayner SL, Sundaramoorthy V, Dobson-Stone C, Molloy MP, van Blitterswijk M, Dickson DW, Petersen RC, Graff-Radford NR, Boeve BF, Murray ME, Pottier C, Don E, Winnick C, McCann EP, Hogan A, Daoud H, Levert A, Dion PA, Mitsui J, Ishiura H, Takahashi Y, Goto J, Kost J, Gellera C, Gkazi AS, Miller J, Stockton J, Brooks WS, Boundy K, Polak M, Muñoz-Blanco JL, Esteban-Pérez J, Rábano A, Hardiman O, Morrison KE, Ticozzi N, Silani V, de Belleroche J, Glass JD, Kwok JB, Guillemin GJ, Chung RS, Tsuji S, Brown RH Jr, García-Redondo A, Rademakers R, Landers JE, Gitler AD, Rouleau GA, Cole NJ, Yerbury JJ, Atkin JD, Shaw CE, Nicholson GA, Blair IP. CCNF mutations in amyotrophic lateral sclerosis and frontotemporal dementia. Nat Commun. 2016 15;7:11253.
  12. Don EK, de Jong-Curtain TA, Doggett K, Hall TE, Heng B, Badrock AP, Winnick C, Nicholson GA, Guillemin GJ, Currie PD, Hesselson D, Heath JK, Cole NJ. Genetic basis of hindlimbs loss in naturally occurring vertebrate model. Biol Open. 2016 18;5(3):359-66.


Oral Presentations:

  1. Kennerson ML, Brewer MH, Drew A, Cutrpi A, Albulym O, Siddell, A and Nicholson GA Genomics in Inherited Peripheral Neuropathies – What is next generation sequencing telling us about inherited neruopathies? 15th Asian and Oceanian Congress of Neurology. Kuala Lumpur, Malaysia, August 2016.
  2. Nicholson GA, Kennerson ML, Perez-Siles G, Ryan MM and Chuang D CMT and other inheritated peripheral neuropathies: clinical perspective. 15th Asian and Oceanian Congress of Neruology. Kuala Lumpur, Malaysia, August 2016.
  3. Siddell A, Albulym O, Perez-Siles G, Brewer MH, Nicholson GA and Kennerson ML* Investigating the functional consequences of microrchidia 2 (MORC2) mutations causing axonal CMT (CMT2Z). The 6th International Charcot-Marie-Tooth and Releated Neuropathy Consortium (CMTR) Meeting, Venice, Italy, September 2016. *Presenter
  4. Drew AP, Cutrupi AN, Brewer MH, Nicholson GA and Kennerson ML An intrachromosomal translocation inserts a 1.35 megabase DNA fragment into chromosome 7q34-q36.2 DHMN1 locus. The 6th International Charcot-Marie-Tooth and Releated Neuropathy Consortium (CMTR) Meeting, Venice, Italy, September 2016.
  5. Kennerson ML*, Drew* AP, Cutrupi AN, Brewer MH and Nicholson GA Identification of a 1.35 Mb insertion within the distal hereditary motor neuropathy locus (DHMN1) on chromosome 7q34-q36.2. 65th American Society of Human Genetics, Vancouver, Canada, October 2016. * equal first authors
  6. Perez-Siles and Kennerson ML Atp7aT985I, a conditional knock-in mouse to unravel the role of copper in X-linked distal hereditary motor neuropathy (dHMNX). Biometals Symposium, Florey Institute of Neuroscience and Mental Health, Melbourne Victoria, October 17 2016.
  7. Kennerson ML Looking beyond the exome: novel structural variation (SV) mutations causing inherited peripheral neuropathies. International Conference of the genetics Society of Korea. Jeju Island, Korea, November 10-11 2016.
  8. Kennerson ML Hereditary neuropathy from gene to therapy. Sydney Neurophsiology Workshop in association with ANZAN, Sydney, New South Wales November 19-20 2016.

Poster Presentations:

  1. Drew AP, Cutrupi AN, Brewer MH, Nicholson GA and Kennerson ML Whole genome sequencing identifies a 1.35 Mb insertion into the DHMN1 locus on chromosome 7q34-q36.2. Australian Society of Medical Research (ASMR) NSW Scientific Meeting, Sydney, Australia, June 2016.
  2. Cutrupi AN, Drew AP, Brewer MH, Nicholson GA and Kennerson ML Use of patient lymphoblasts to prioritise candidate distal hereditary motor neuropathy genes for developing cell and animal models of motor neuropathy. Australian Society of Medical Research (ASMR) NSW Scientific Meeting, Sydney, Australia, June 2016.
  3. Siddell A, Albulym O, Perez-Siles G, Brewer M, Nicholson G and Kennerson ML Understanding the molecular pathways of neurodegeneration in a new form of CMT. Australian Society of Medical Research (ASMR) NSW Scientific Meeting, Sydney, Australia, June 2016.
  4. Ahmad Annuar A, Tey S, Shahrizaila N, Samulong S, Goh KJ, Drew A, Nicholson G and Kennerson ML Whole exome sequencing of a Malaysian family with CMT reveals a novel candidate gene for autosomal recessive CMT. 15th Asian and Oceanian Congress of Neruology. Kuala Lumpur, Malaysia, August 2016.
  5. Kanhanged M, Cornett K, Subramanian G, Ryan M, Young H, Smith R, Ouvrier R, Nocholson G, Kennerson M, Burns J and Menezes M Clinical and neurophysiological profile of CMTX3 in childhood. ANZCNS 5th Annual Scientific Meeting, Auckland, New Zealand, September 2016.
  6. Brewer MH, Neumann B, Webby R, Siddell A, Kidambi A, Nicholson GA and Kennerson ML Using worms to screen for novel gene mutations causing inherited peripheral neuropathy: a validation study. The 6th International Charcot-Marie-Tooth and Releated Neuropathy Consortium (CMTR) Meeting, Venice, Italy, September 2016.
  7. Menezes M, Ellis M, Abdel-Salam G, De Carvalho D, De Goede C, Kaymakamzade B, Sawaya R, Swoboda K, Willemsen M, Crow Y and Kennerson ML Clinical and neurophysiological profile of peripheral neuropathy in Aicardi-Goutieres syndrome. The 6th International Charcot-Marie-Tooth and Releated Neuropathy Consortium (CMTR) Meeting, Venice, Italy, September 2016.

Research Grants




Total $$


Sydney Medical School Tony Basten Fellowship Scheme

Gonzalo Perez-Siles

Using induced pluripotent stem cells (iPSC) technologies to study hereditary motor neuropathy caused by ATP7A mutations in neuronal cell models

 $   50,000


CMT Association of Australia

Marina Kennerson

Modelling a novel disease mechanism for distal hereditary motor neuropathy (DHMN1) on chromosome 7 using induced pluripotent stem cell (iPSC) technology

 $   10,000


Contact details for department

Head of Department: Professor Garth Nicholson

Department/Unit: Neurobiology and Molecular Medicine
Clincal Sciences Building (C22)
Hospital Rd
Concord NSW 2139
Telephone: (02) 9767 6796
Facsimile: (02) 9767 6991
Web: www.slhd.nsw.gov.au/research/
Email: marinak@anzac.edu.au