Circular RNAs and their Role in Amyotrophic Lateral Sclerosis

Location: Remote, based at the Candidate’s University

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.

Iggy Get Out are currently performing deep phenotyping on patients with sALS and have gathered whole genome sequencing, RNA expression, DNA methylation and protein expression data. However, they have not been able to assess the expression levels of circular RNA (circRNA) in these patients. Given that circular RNAs are abundant and evolutionally conserved, they would very much like to probe their association with, and relevance to sALS.

Research to be Conducted

Initially, you will be asked to perform differential expression analysis of circular RNA in a very small cohort of sALS patients and healthy controls. This can be done using CircMaker, CIRCPlus, circtools or another algorithm of your own choosing/design. If you are successful in this leg of the project, we would also like you to perform a similar analysis on a large cohort of sALS patients (approximately 540 patients) acquired from the New York Genome Project. Some tertiary analysis of any differentially expressed circRNAs should also be performed. Iggy Get Out would like to know if there is any complementarity with mature miRNAs, or other genes. Mapping differentially expressed circRNAs to the genomic regions from which they arose should also be performed. Iggy Get Out are happy to accommodate tertiary analysis strategies recommended/developed by the intern.

Skills Required

We are looking for a PhD student with the following:

ESSENTIAL

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

DESIRABLE

  • Understanding of biological pathways

Expected Outcomes

Iggy Get Out expect to have lists of differentially expressed circRNAs from their own small cohort and the larger NY Genome cohort by the end of the project. Regarding tertiary analysis, the minimum expected outcomes are that the circRNAs be mapped to the region of the genome from which they have come. Seed sequence analysis should also be performed to determine whether any circRNAs of interest contain binding sites for mature microRNAs, or if the circRNAs contain any miRNAs themselves. Iggy Get Out 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

Reference

APR – 1067