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Student opportunities at the Perron Institute

A major strategic goal of the Perron Institute is to provide student opportunities for young scientists. Many of our academic staff supervise postgraduate students for Masters by Research and PhD Degrees.

Each research project is tailor-made for the student after discussion with the relevant research group head.

Areas of Research

The areas of research for potential students include:
•    Molecular genetics – Professor Steve Wilton and Professor Sue Fletcher
•    Nucleic Acid Therapeutics – Drug targeting for the diagnosis and treatment of neurological conditions – Dr Rakesh Veedu
•    Stroke –  Adj/A/Professor Bruno Meloni
•    Restorative Neurology – Clinical Professor Soumya Ghosh
•    Demyelinating Diseases – MS – Clinical Professor Allan Kermode

Working With Universities

The Perron Institute works closely with the following Universities in enrolling students:
•    University of Western Australia
•    Murdoch University
•    Notre Dame University
•    Edith Cowan University
•    Curtin University

Enquiries

For general Masters by Research and PhD enquiries please email Professor Norman Palmer:

norman.palmer@perron.uwa.edu.au

or call: 08 6457 0301.

Becoming a student at the Perron Institute

The Perron Institute is in the process of expanding its research as it moves into the new Sarich Neuroscience Research Institute building in 2017. As part of this expansion, new student opportunities continue to emerge for PhD, Masters by Research and Honours students whose goal is to become members of the next generation of outstanding medical researchers focusing on neurological and neuromuscular disorders.

In partnership with universities across Perth, including the University of Western Australia, Murdoch University, Curtin University, Edith Cowan University and with links to Notre Dame University, the Perron Institute provides a supportive learning environment for students engaged in research studies.

As one of the world’s leading medical research institutes in the field of molecular therapies for neuromuscular disorders and with research strengths in stroke, multiple sclerosis, nucleic acid therapeutics, motor neurone disease and restorative neurology, the Perron Institute has an outstanding track record of translating findings from the research laboratory into outcomes that directly improve health care and quality of life.

The Perron Institute values its students for their contribution to new ideas and discoveries as well as to the life of the Institute as a whole.

We look forward to you joining us in our quest to combat the neurological disease through research. Please contact norman.palmer@perron.uwa.edu.au if you are a prospective PhD or Masters by Research and are interested in studying at the Perron Institute.

The Perron Institute Prestige Scholarships

To mark the Perron Institute’s move into the Sarich Neuroscience Research Institute building in 2017, the Institute is pleased to announce the introduction of the the Perron Institute Prestige Scholarships program.

Five the Perron Institute Prestige Scholarships will be awarded annually over the 5 years 2017-2021 to students commencing their PhDs under the supervision of a the Perron Institute researcher(s). To be eligible, students must:

  • Have been accepted as a PhD student by one of the Perron Institute research staff; and,
  • Hold at the time of commencement of their PhD studies an Australian Postgraduate Award (APA), International Postgraduate Research Scholarship (IPRS) or equivalent postgraduate research scholarship tenable at a Western Australian university.

Students are encouraged to apply for a the Perron Institute Prestige Scholarship at the same time as they apply for an APA, IPRS or other scholarship.

A the Perron Institute Prestige Scholarship will provide a top-up living allowance scholarship of $10,000 per year for the duration of the degree as well as $5,000 towards conference and other research-related travel costs. The closing date for applications for the Perron Institute Prestige Scholarships for commencement in 2017 in Friday 28 October 2016.

Contact norman.palmer@perron.uwa.edu.au for information on how to apply.

Information on research projects for PhD and Masters by Research students at the Perron Institute is shown below.

Research Project Areas

STROKE

Supervisors: Associate Professor Bruno Meloni and Clinical Professor Neville Knuckey

The Stroke Research group has demonstrated that poly-arginine and arginine-rich peptides have potent neuroprotective properties in in vitro injury models that mimic the effects of stroke (e.g. excitotoxicity), as well as in animal stroke models. Due to the effectiveness of these arginine-rich peptides following stroke, it is anticipated that this class of peptide will also possess neuroprotective actions in other acute and chronic neurological disorders such as global cerebral ischaemia, brain trauma (TBI), perinatal hypoxia-ischaemia, spinal cord injury (SCI), Alzheimer’s disease, and motor neuron disease.

Our primary focus is the application of arginine-rich peptides to limit CNS injury after stroke and other acute neurological disorders. In our stroke models we are investigating the effectiveness of the peptides to extend the therapeutic window and minimize reperfusion injury following re-canalisation therapy (e.g. tPA thrombolysis and thrombectomy). In addition, studies are underway or planned to assess the effectiveness of arginine-rich peptides in animal models of TBI, perinatal hypoxia-ischaemia, and SCI. We are also developing arginine-rich peptides that are resistant to proteolysis so that they are suitable for future oral administration to treat chronic neurodegenerative disorders and to improve recovery after acute CNS injuries.

PhD PROJECTS

Investigate the effectiveness of arginine-rich peptides to extend the therapeutic window and reduce reperfusion injury following re-canalisation in stroke

This project will perform peptide dose trials to investigate the effectiveness of arginine-rich peptides to extend the therapeutic window and minimise reperfusion injury following re-canalisation in stroke. The project will evaluate different peptides and administration routes (intravenous versus intra-arterial).

Assessment of peptides to improve recovery following CNS injury

In addition to reducing injury, there is evidence that arginine-rich peptides can improve recovery after acute brain and SCI injury. This project will investigate the effectiveness of arginine-rich peptides to improve recovery when administered several days after an acute brain injury. For example, three to five days following an acute CNS injury (stroke, TBI or SCI), peptides will be administered intraperitoneally for one to four weeks during which time animals will be assessed for functional improvement.

Investigate the stability, pharmacokinetics and effectiveness of modified arginine-rich peptides when administered orally in normal rats and in rats subjected to a stroke

This project will investigate the effectiveness of arginine-rich peptides to improve recovery when administered several days after an acute brain injury. For example, three to five days following an acute CNS injury (stroke, TBI or SCI), peptides will be administered intraperitoneally for one to four weeks during which time animals will be assessed for functional improvement.

Investigate the effectiveness of arginine-rich peptides to improve stroke outcomes in female rats, aged rats and in long-term functional studies

This project will perform peptide dose trials to investigate the neuroprotective effectiveness of arginine-rich peptides in female and aged rats subjected to stroke. In addition, ability of arginine-rich peptides to provide long-term functional and histological benefits will also be investigated.

Investigate the effectiveness of arginine-rich peptides to reduce injury and improve outcomes following SCI.

In addition to the potential to reduce injury following SCI, there is evidence that arginine-rich peptides can improve recovery. This project will perform peptide dose trials to investigate the effectiveness of arginine-rich peptides to reduce injury and to improve recovery after SCI.

NUCLEIC ACID THERAPEUTICS

Supervisor: Dr Rakesh Veedu

Nucleic Acid Therapeutics research focuses on theranostics, the science that brings together therapeutics and diagnostics (therapeutics and diagnostics = theranostics). Research in our laboratory is focused on developing novel personalised precision therapeutics and diagnostics using novel nucleic acid-based technologies targeting an array of human diseases, including neuromuscular diseases and solid cancers. To achieve this end, we utilise the applicability of novel functional nucleic acids (FNAs), such as nucleic acid aptamers and various other therapeutic nucleic acids including antisense oligonucleotide (AO), short interfering RNAs (siRNAs), DNAzymes and microRNA targeting oligonucleotides (anitmiRs). Specifically, we construct designer nucleic acid drug candidates by conjugating novel therapeutic nucleic acids that target the underlying molecular pathological hallmarks of the disease, with nucleic acid aptamers as a delivery cargo for tissue specific delivery to relevant disease-specific sites within the body to maximise efficacy and minimise toxicity and adverse side effects. For developing successful nucleic acid-based drugs, the use of chemically-modified nucleotides is essential in order to improve the pharmacokinetic properties. To this end, we routinely synthesise nucleic acid sequences with various chemical modification including locked nucleic acids nucleotides (LNA), 2’-O-Methyl RNA nucleotides (2’-OMe) and 2’-Fluoro RNA nucleotides (2’-F), using two state-of-the-art oligonucleotide synthesisers.

Nucleic Acid Therapeutics

Available PhD Projects:

  1. Development of novel branched therapeutic oligonucleotide constructs capable for simultaneous delivery and therapy of neuromuscular diseases and solid cancers.
  2. Development of smart chimeric aptamers for tackling neuromuscular diseases and solid cancers.

MOLECULAR THERAPIES

Supervisors: Professor Steve Wilton and Professor Sue Fletcher

The Molecular Therapies Laboratory based in the Centre for Comparative Genomics at Murdoch University has been at the forefront in the development of personalised treatments for serious inherited and acquired conditions. We are well positioned to become a pipeline for drug development by designing antisense oligonucleotides, genetic drugs capable of altering gene expression and bypassing disease-causing mutations.

The majority of human genes undergo “splicing” during gene expression, a process where exons are precisely joined together and noncoding introns are removed. At least three quarters of our gene transcripts undergo alternative splicing, allowing an increased diversity of gene expression by using different exon combinations in a developmental or tissue-specific manner. We have shown it is possible to re-direct gene transcript processing, in essence “therapeutic alternative splicing” to treat human disease.

Our Duchenne muscular dystrophy program is the most advanced, with one compound, eteplirsen currently in Phase 2 and 3 clinical trials, and FDA approval is pending. Extended Phase 2 clinical trials evaluating eteplirsen have shown altered natural history of this devastating muscle wasting disease, and we are now exploring opportunities to treat other inherited and acquired conditions, in addition to neuromuscular diseases.

An estimated 25% of pathogenic nonsense and missense mutations have been found to alter premRNA splicing, and loss of exon recognition has been identified as a common mechanism of gene dysregulation. We believe that antisense oligonucleotide mediated alternative splicing can be developed to treat selected mutations causing many genetic disorders.

Research projects will study the processes of constitutive and alternative splicing, modifier genes and characterize diseasecausing gene lesions to develop appropriate antisense therapies for:

  • Duchenne muscular dystrophy (therapeutic delivery, protein modeling, cardiac and respiratory aspects)
  • Spinal muscular atrophy (arising from SMN deficiency)
  • Collagenopathies (epidermolysis bullosa, osteogenesis imperfecta, Alport syndrome)
  • Cystic fibrosis (selected mutations that compromise normal splicing).
  • Pompe’s disease (adult onset)
  • Triplet repeat expansion diseases (Freidriech’s ataxia, Huntington’s disease, myotonic dystrophy, spinocerebellar ataxias)
  • Motor neuron disease/amyotrophic lateral sclerosis
  • Mutations that disrupt normal splicing and lead to inherited disorders (congenital muscular dystrophy, limb girdle muscular dystrophy, laminopathies, enzyme deficiencies)

Techniques

  • cell culture techniques, propagation, differentiation, transfection and cryo-storage
  • molecular biology techniques including DNA/RNA extraction and analysis,
  • bioinformatics, biobanks, disease registries, in silico modeling
  • antisense oligomer design, synthesis and evaluation
  • protein analysis, enzyme assays, immunohistochemical staining, western blotting

RESTORATIVE NEUROLOGY

Supervisor: Clinical Professor Soumya Ghosh

At the Centre for Restorative Neurology, we study neural mechanisms of brain plasticity and recovery of function from brain injury. Our team has a diverse background involving neurology, physiotherapy, psychology and physics. We use non-invasive brain stimulation (Transcranial Magnetic Stimulation) to study pathophysiology of cerebral dysfunction in stroke, multiple sclerosis and Parkinson’s disease. In clinical trials, we investigate the use of new therapeutic options provided by non-invasive brain stimulation (Transcranial Magnetic Stimulation, Transcranial Direct Current Stimulation) in neurological disorders. Brain stimulation is combined with physical therapy to enhance neuroplasticity and motor learning. We use computerised robots for treatment and assessment, the MIT-Manus Inmotion Arm and Hand Robot for upper limb therapy and the Balance Master (computerised posturography) for analysing and improving balance and lower limb function.

Current research projects appropriate for PhD projects:

Clinical trials

  1. Enhancing recovery of function after stroke – combined use of physical training (robot-assisted arm therapy) with non-invasive brain stimulation (the Perron Institute)
  2. Enhancing balance and gait in patients with Multiple Sclerosis – combined use of balance training with non-invasive brain stimulation (the Perron Institute)

Scientific studies

  1. Mechanisms of action of DBS in movement disorders: Local Field Potential analysis and TMS studies (SCGH)

DEMYELINATING DISEASES

The Demyelinating Diseases Research Group is focused on characterisation of the clinical, laboratory, radiological and genetic aspects of multiple sclerosis (MS). Clinical measures in MS are imprecise and the disease proceeds over decades with immensely variable phenotype and progression.

The Perth MS cohort is a large longitudinal cohort of highly characterised patients, numbering over 1,600 cases and covering the entire spectrum of disease phenotypes. Our research is conducted within an ethical environment where patients with MS have received and continue to receive cutting edge high quality clinical management and intervention, with early access to evidence based therapies. Our service provision integrates closely with allied health specialists from various hospital agencies, teaching hospitals and the Multiple Sclerosis Society of Western Australia.

In addition to our own cutting edge clinical, radiological, genetic, epigenetic, serological and immunological studies in MS, we have been engaged in many collaborative ventures both in Australia and overseas that have been recognised in peer-reviewed publications. We are undertaking collaborative work with the genetic data from the IMSGC, ANZGENE and Wellcome Trust.

Over time our Group has been involved in a number of Clinical Drug Trials including JEMS, ESTEEM, EARLIMS, BEYOND, CORAL, STARS, SURPASS, RECORD, STRATIFY, TAPPS, INNATE, PrevANZ, The Linomide Study, PROGRESS, COPERNICUS, the Haematological Stem Cell Transplant Program for Refractory MS, and we have provided a Fingolimod Start Up Clinic at the the Perron Institute, which is free of charge to patients with MS.

Development of biomarkers for progressive MS based on clinical, radiological and laboratory measures of disease progression.

As a member of Progressive MS Alliance, we are engaged in development and assessment of putative biomarkers of progressive disease. The absence of an early, reliable indicator of progressive disease is a critical question. Two PhD projects will focus on developing biomarkers for progressive MS based on clinical, radiological and laboratory measures of disease progression. The study will sub-categorise progressive patients into those with and without clinical and/or MRI activity. This distinction between those with inflammatory activity and those without may prove to be of considerable importance, not only in choosing therapies, but also in determining whether there are multiple mechanistic pathways to progressive disease. The aim of two PhD proposals will be to determine the earliest, most reliable indicators of secondary progressive disease.

Our Recent PhD Graduates

One of the Perron Institute’s most important functions is training the neuroscientists of tomorrow through its innovative PhD program. Over the years, the Perron Institute has produced a succession of PhD graduates who have gone to occupy important positions in research organisations, universities and industry. Over the last four years, the Perron Institute has produced eight PhD graduates.

In 2016 Gurkiran Flora graduated.

Gurkiran Flora’s PhD studies focused on the deadly brain tumor, glioblastoma (GBM), exploring the role of cyclophilin A, a protein know to be secreted by cells in response to stress. Gurkiran’s studies demonstrated for the first time that oxidative and inflammatory stress stimulate the secretion of cyclophilin A by microglia, the cells that form the brain’s primary immune defense system. These findings suggest that cyclophilin A plays a key role in the progression of GBM and suggests that drugs targeting cyclophilin A may provide a new approach to the treatment of the disease. Gurkiran is now part of the 2016 Graduate Development Program at the Department of Health.

In 2014, there were three PhD graduates, Jonathan Teoh, Ryan Anderton and Yuebei (‘Robyn”) Luo.

  • Jonathon Teo’s PhD focused on the way some key mitochondrial proteins respond to the type of ischaemic injury seen in stroke. The research provided new insights into the aetiology of stroke, in particular showing that one mitochondrial protein in particular has a potent neuroprotective action. Jonathan is now a Lecturer at the University of Nottingham Malaysia Campus.
  • Ryan Anderton’s PhD studied the neurodegenerative disorder, spinal muscular atrophy (SMA), which represents the most common genetic form of infant death. In particular, it explored the role of the survival of motor neuron (SMN) protein and demonstrated that SMN expression prevents programmed cell death (apoptosis). Ryan is now a Senior Lecturer at Notre Dame University. 
  • A medical graduate by background, Robyn Luo studied the molecular basis of the disease inclusion body myositis (s-IBM), the most common form of inflammatory myopathy in the over 50s. Robyn has returned to China and is now working at Shandong University.

In 2013, there were four PhD graduates, Bernadette Majda, Wei-Peng Teo, Arada Rojana-Udomsart and Liam Johnson.

  • Bernadette Majda is currently a Research Associate in the UWA School of Anatomy, Physiology and Human Biology. Her PhD explored the processes associated with cerebral ischemia and stroke, including the role of the proteins, sodium-calcium exchanger and cyclophilin, and the neuro-protective effects of magnesium.
  • Wei-Peng Teo’s PhD focused on the use of non-invasive brain stimulation to understand central changes to the brain in patients with movement disorders and stroke. His studies confirmed that neuro-modulation augments motor learning both in healthy subjects and patients. After a period as a postdoctoral fellow at the National University of Singapore, Wei-Peng Teo now lectures in Exercise and Sports Sciences at Central Queensland University.
  • A medical graduate of Mahidol University in Bangkok and a consultant neurologist by background, Arada Rojana-Udomsart’s PhD explored the pathogenesis of inclusion body myositis (s-IBM), including the role of histocompatibility and other genes in autoimmunity. Medical science is not totally without its romantic side. Whilst at the Perron Institute, Arada met and subsequently married another Thai PhD student, Wai Mitrpant. Arada and Wai now have a son and are working in Thailand.
  • Liam Johnson’s PhD investigated postural dysfunction in Parkinson’s disease sufferers and explored ways in which interventions to improve balance (including Pilates training) are beneficial. After spending several years in a teaching role at Charles Darwin University, Liam is now a Postdoctoral Research Fellow at Victoria University of Technology where he is currently collaborating with researchers from the Florey Institute.

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