Accumulated Small Mutations as Contributors to Amyotrophic Lateral Sclerosis

Location: Darlinghurst, Sydney, NSW

Duration: 3 months

Proposed start date: ASAP

Project Background

Amyotrophic Lateral Sclerosis (ALS) is a relentlessly progressive neurodegenerative disease that typically causes death due to respiratory failure within 3 – 5 years of diagnosis. To make matters worse, most ALS patients suffer from the sporadic form of the disease (sALS) for which no cause, genetic or otherwise can be deduced. Current research in the field indicates a wide variety of genetic, epigenetic and transcriptional changes all contribute to the development and progression of the disease. This suggests a personalised medicine approach is needed to identify actionable therapeutic candidates from individual patients. Based on recent findings from Iggy Get Out’s own studies, they hypothesise that mutations in a particular set of biological pathways are common and potentially pathologically relevant in ALS.

Research to be Conducted

Iggy Get Out are seeking a talented bioinformatician that can help them explore this hypothesis in a large cohort of approximately 500 ALS patients and a similar number of healthy controls.

You will be required to perform eQTL analysis using this cohort in order to identify mutations in genes across the genome. From here you will need to perform gene set enrichment analysis to identify pathways that bear numerous mutations compared to the healthy cohort. You will need to perform statistical analyses to determine which pathways are most affected, and which genes are most relevant in these pathways. Tertiary analysis aimed at defining potential loss/gain of function in the affected biological pathways should be performed next with the aim of identifying potential dysfunction caused by any mutations deemed to be of interest.

Skills Required

We are looking for a PhD student with the following:


  • Knowledge and training in biostatistics
  • Fluency in R and Python


  • Understanding of biological pathways

Expected Outcomes

Iggy Get Out expect to be able to support or reject their hypothesis based on the findings of this study. If the hypothesis is supported, the tertiary analysis steps should also be completed. They also expect to obtain from the intern all experimental data and a copy of their experimental notes which must be annotated correctly, dated appropriately and signed by the institution supervisor, or a member of Iggy staff. They intend to publish the results at the conclusion of the study. Provided the intern writes the first draft of the paper, they will have first authorship. The intern will have the opportunity to work with experienced bioinformaticians and molecular biologists at Iggy Get Out.

Additional Details

The intern will receive $3,000 per month of the internship, usually in the form of stipend payments.

It is expected that the intern will primarily undertake this research project during regular business hours, spending at least 80% of their time on-site with the industry partner.  The intern will be expected to maintain contact with their academic mentor throughout the internship either through face-to-face or phone meetings as appropriate.

The intern and their academic mentor will have the opportunity to negotiate the project’s scope, milestones and timeline during the project planning stage.

Applications Close

4 September 2019


APR – 1066