Developing algorithms for single-cell long-read nanopore sequencing

About the Project

Project Description

Alternative splicing (AS) is one of the most powerful mechanisms generating protein diversity in the human brain. Dysregulation of splicing is increasingly recognised as a major driver of neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and hereditary spastic paraplegia (HSP). Yet, understanding how individual splice isoforms alter protein structure and neuronal function has been limited by short-read sequencing and a lack of structural context.

This PhD project will develop and apply computational frameworks that integrate single-cell long-read (Oxford Nanopore) transcriptomics with AlphaFold protein structure prediction to reveal how alternative splicing remodels protein structure, localisation, and interaction networks in the human nervous system.

Single-cell nanopore sequencing enables the direct observation of full-length transcripts from individual cells — providing unprecedented resolution of isoform diversity in complex tissues such as the brain. AlphaFold offers near-experimental accuracy in protein structure prediction, allowing the student to model how specific exon inclusion or exclusion events reshape domains and molecular interfaces.

By combining these approaches, the project aims to:

• Identify disease-relevant isoform switches in ALS and related neurodegenerative disorders
• Predict their structural and functional consequences using AlphaFold and large-scale molecular modelling
• Develop novel algorithms and visualisation tools to integrate transcriptomic and structural data for therapeutic target discovery

This is an ideal project for bioinformatics candidates interested in AI-driven biology, RNA regulation, and computational neurogenomics.

Training and Environment

The student will join the Neurotranscriptomics Laboratory led by A/Prof Robert Weatheritt at the Garvan Institute of Medical Research (Sydney, Australia), affiliated with UNSW Sydney and EMBL Australia.

The Garvan Institute hosts world-class facilities in genomics, imaging, and computational biology. Students will gain hands-on experience in:

• CRISPR-dCas9 Perturb-Seq screening
• Single-cell and long-read (Nanopore) transcriptomics
• Computational analysis and machine learning for network biology

The candidate will be embedded in an interdisciplinary team spanning computational biology, neurogenetics, and RNA therapeutics, with opportunities for collaboration across EMBL Australia

Candidate Requirements

• Academic background: Honours (First Class) or Master’s degree in bioinformatics, computational biology, molecular biology, or neuroscience.
• Essential skills: Strong bioinformatics or data-science experience (e.g. single-cell or nanopore transcriptomics).
• Desirable skills: Knowledge of RNA biology, or neurodegenerative disease.
• Eligibility: Applicants should hold a degree from a top-200 ranked university to be competitive for international scholarships (UNSW, RTP).
• Publications or demonstrable research output are advantageous.

How to Apply

Email A/Prof Robert Weatheritt (r.weatheritt@garvan.org.au) with:

1. A current CV
2. Academic transcripts
3. A short statement of research interests and motivation

Shortlisted applicants will be invited for interview and supported to apply for competitive international scholarships through UNSW Sydney or EMBL Australia.

Funding Notes

Applicants must hold an honours or masters degree from a top-200 ranked university to be competitive for international scholarships (e.g., UNSW/ RTP). Competitive applicants will receive full tuition coverage and a living stipend (approximately AUD $43,000-$50,000 per year).