10x Genomics Chromium System

Background

The University of Newcastle, in partnership with the Hunter Medical Research Institute (HMRI), is a national leader in several fields of medical research being ranked in the top eight in Australia for all Biomedicine (Leiden Rankings). The University and HRMI have the largest respiratory research centre in Australia (including the Centre for Excellence in Severe Asthma), provide leadership in cancer genomics research, and host a major centre for brain and stroke research.

This revolutionary technology allows never before seen resolution of genetic networks at the single cell level, which provides tremendous potential for new insights into human disease pathogenesis. Many researchers at the University of Newcastle and HMRI are now able to identify new diagnostics and new targets for therapy in a range of human diseases by using this transformative single cell platform.

Aims & Objectives

The equipment enables medical researchers to investigate patient biopsies at the single cell level to define disease-specific gene expression changes in tens of thousands of individual cells. This data can identify new molecules and cell types that could be targeted for therapy and new biomarkers to be used as advanced diagnostics in precision medicine.

Approach

Researchers across the University and HMRI have been encouraged to use single cell sequencing technology as a methodology to improve discovery of new treatments and diagnostics for a range of chronic diseases.

The major disease research areas at the University and HMRI utilising this equipment include respiratory diseases, with a focus on severe asthma and Chronic Obstructive Pulmonary Disease (COPD), cancer research on both solid tumours and leukaemia, chronic inflammatory bowel disease, and neurological disorders and stroke. All these diseases have an urgent need for new therapies as they are either life-threatening conditions without treatment or current therapies that need to be significantly enhanced to provide improved patient outcomes.

All researchers trained in using this equipment benefit from the attainment of a new skill set in an area of cutting edge medical research These new skills and access to the equipment will lead to a significantly increased ability to propose novel medical research projects previously not feasible and lead to the identification of new drug targets and disease diagnostics over time.

Outcomes

The first project to use the equipment involved sequencing and comparing the transcriptome of 10,000 individual airway cells from patients with and without asthma, aiming to identify the key genes that cause asthma and discover new types of cells that could be targeted to effectively treat asthma.

This project was completed in mid-2019 with molecular targets identified undergoing further investigation as potential drug targets. This subsequent research will form part of a 2020 NHMRC Ideas Grant.

In addition, a further eight researchers used this equipment in its first year. Research undertaken using the equipment has been very diverse including studies on the following diseases for both discovery and translational research:

• Leukaemia
• Asthma
• Chronic Obstructive Pulmonary Disease
• Endometriosis
• Male infertility
• Stroke.

A further six research projects (subject to funding) were also identified as requiring use of this equipment within 12 months of installation.

Impact

Researchers will be using this technology for investigations to identify a predictive biomarker of patient response to monoclonal antibody therapy. This work with the 10X equipment has recently attracted a $430,000 commercial contract from a multinational pharmaceutical company to conduct this biomarker study in a large clinical trial cohort.

Use of this equipment was an integral part of two successful NHMRC grants in 2019.