Gene-environment interactions in ALS

Defining gene-environment interactions in amyotrophic lateral sclerosis using isogenic iPSC

Degree type

PhD

Closing date

10 October 2022

Campus

Hobart

Citizenship requirement

Domestic/International

About the research project

ALS can develop due to interactions between an individual’s genetics and the environment in which they live, where the culmination of lifestyle and genetic factors increases the person’s risk of developing ALS. This gene-environment interaction can be thought of as an individualised multistep process, where predisposing genetic risk variants and environmental factors each contribute one or more ‘steps’ that increase the likelihood of a person developing ALS. Although we have considerable epidemiological evidence supporting this multistep process, we lack detailed knowledge of how genetic risks combine with one or more environmental steps to cause motor neurons to die. In this project we will systematically breakdown these steps to investigate what cellular pathways are activated by ALS-relevant gene-environment interactions, and how these cause motor neurons to become dysfunctional and die. We will use human stem cells to grow motor neurons in a dish, and genetically alter these neurons to carry genes associated with familial or sporadic ALS - modelling the first ‘steps’ in the multistep process. Exposure of these neurons to a variety of environmental factors known to be risk factors for ALS, including cholesterol, neurotoxins and increased cellular activity, will contribute additional ‘steps’. We will document changes to neuron shape, activity and function, cellular processes, gene expression and genome organisation, to identify key cellular changes that occur as cells become increasingly aberrant in response to gene-environment interactions. This work will help us understand how ALS develops and why cells are vulnerable to genetic and environmental interactions.

Primary Supervisor

Meet A/Prof Tony Cook

Funding

Applicants will be considered for a Research Training Program (RTP) scholarship or Tasmania Graduate Research Scholarship (TGRS) which, if successful, provides:

  • a living allowance stipend of $28,854 per annum (2022 rate, indexed annually) for 3.5 years
  • a relocation allowance of up to $2,000
  • a tuition fees offset covering the cost of tuition fees for up to four years (domestic applicants only)

If successful, international applicants will receive a University of Tasmania Fees Offset for up to four years.

As part of the application process you may indicate if you do not wish to be considered for scholarship funding.

Eligibility

Applicants should review the Higher Degree by Research minimum entry requirements.

Additional eligibility criteria specific to this project/scholarship:

  • Applications are open to Domestic/ International/ Onshore applicants
  • Applications are open to applications from neuroscience/cell biology/molecular biology disciplines or similar background only
  • Applicants must be able to undertake the project on-campus

Selection Criteria

The project is competitively assessed and awarded.  Selection is based on academic merit and suitability to the project as determined by the College.

Additional essential selection criteria specific to this project:

  • Strong communication skills
  • Strong record keeping skills
  • Familiar with PC2 laboratory research

Additional desirable selection criteria specific to this project:

  • Experience in contemporary cell-based techniques, particularly iPSC culture and differentiation, and/or CRISPR/Cas gene editing
  • Experience in image-based analyses

Application process

There is a three-step application process:

  1. Select your project, and check you meet the eligibility and selection criteria;
  2. Contact the Primary Supervisor, A/Prof Tony Cook to discuss your suitability and the project's requirements; and
  3. Submit an application by the closing date listed above.
    • Copy and paste the title of the project from this advertisement into your application. If you don’t correctly do this your application may be rejected.
    • As part of your application, you will be required to submit a covering letter, a CV including 2 x referees and your project research proposal.

Following the application closing date applications will be assessed within the College. Applicants should expect to receive notification of the outcome by email by the advertised outcome date.

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