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Targeting Astrocyte-Mediated Mechanisms Leading to Neuronal Toxicity in Motor Neurone Disease

  • Full or part time
  • Application Deadline
    Monday, September 30, 2019
  • Funded PhD Project (Students Worldwide)
    Funded PhD Project (Students Worldwide)

Project Description

In this project, we propose to investigate the mechanisms by which astrocytes impact motor neuron hyperexcitability in Motor Neurone Disease (MND). Whilst the loss of motor neurons is central to ALS, it is becoming clear that other cell types in the brain (such as astrocytes) contribute to motor neuron degeneration and death. Astrocytes normally exhibit a supportive role for neurons, but in MND their function changes, advancing disease processes. Currently, the precise mechanisms behind the dysfunctional MND astrocyte-mediated neuronal toxicity remain unclear, however evidence from animal and human cell models suggests that preventing astrocyte dysfunction could protect motor neurons from degeneration and death. Thus, our overarching aims are to expose the astrocyte-mediated mechanisms leading to neuronal toxicity in ALS and to use our findings to test potential therapeutics in human cells representing familial and sporadic ALS.

The project will be based at the School of Medicine in Campbelltown Campus with the opportunity to work with Dr Yossi Buskila on novel recording and imaging techniques including patch clamp, optogenetics and two-photon imaging.

We welcome applicants from a range of backgrounds, who are keen to apply their skills to key issues in neurophysiology. In particular, the project is suitable for candidates with strong interests in studying neurobiological disorders and neurodegenerative diseases.

The successful applicant should:

Hold qualifications and experience equal to one of the following (i) an Australian First Class Bachelor (Honours) degree, (ii) coursework Masters with at least 25% research component, (iii) Research Masters degree, or (iv) equivalent overseas qualifications.

Demonstrate strong academic performance in subjects relevant to physiology, neuroscience, neurobiology or neurophysiology.

Be willing to learn electrophysiological and imaging techniques applicable to neurophysiology.
International applicants must demonstrate English language proficiency.

Funding Notes

International candidates will receive a tax-free stipend of $30,000 per annum for up to 3 years to support living costs. Those with a strong track record will be eligible for a tuition fee waiver.

International candidates are required to hold an Overseas Student Health Care (OSHC) insurance policy for the duration their study in Australia. This cost is not covered by the scholarship.

References

1. Buskila Y, Kékesi O, Bellot-Saez A, et al (2019) Dynamic interplay between H-current and M-current controls motoneuron hyperexcitability in amyotrophic lateral sclerosis. Cell Death Dis 10:310. doi: 10.1038/s41419-019-1538-9

2. Alba Bellot-Saez, Greg Cohen, André van Schaik, Lezanne Ooi, John W. Morley and Yossi Buskila (2018) Astrocytic modulation of cortical oscillations. Sci.Rep. 8:11565

DOI:10.1038/s41598-018-30003-w

3. Alba Bellot-Saez, Orsolya Kékesi, John W. Morley and Yossi Buskila (2017) Astrocytic modulation of neuronal excitability through K+ spatial buffering. Neuroscience & Biobehavioral Reviews. 77:87-97. doi: 10.1016/j.neubiorev.2017.03.002.

4. Do-Ha Dzung, Buskila Yossi and Ooi Lezanne (2017) Impairments in motor neurons, interneurons and astrocytes contribute to hyperexcitability in ALS: underlying mechanisms and paths to therapy. Molecular Neurobiology. Doi: 10.1007/s12035-017-0392-y

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