Customer Spotlight - A Singular Scientist – Characterisation & Multiomic Profiling of Assoc. Prof. Joseph Powell, Garvan Institute of Medical Research

joseph-powell.jpgSmart-casual, bearded and internationally regarded, Joseph Powell epitomises the successful career academic, but things could have taken a very different turn.  Nearing completion of his PhD at the University of Edinburgh in 2010, he was torn between science or the more lucrative world of finance and sought his Dad's advice: 'How is that even a question?' was the no-nonsense reply!

So as a post-doc, Joseph moved to Brisbane where he helped form and lead the international Consortium for the Architecture of Gene Expression (CAGE). In 2015, he started his own group at the Institute for Molecular Bioscience (IMB) at the University of Queensland, pioneering the use of single cell sequencing to understand genetic control of disease and cell development.

After his stint at IMB, Joseph moved to Sydney, where he now holds a combined appointment; Director of the Garvan-Weizmann Centre for Cellular Genomics (GWCCG), and Deputy Director of the UNSW Cellular genomics Futures Institute.

The GWCCG focuses on both fundamental and translational medical research - a combination of wet lab and computational approaches, with established programs in oncology, immunology, stem cells and lung disease.

'Seeing the possibilities for medical research through the intersection of statistical genetics and stem cell biology has been one of the most rewarding experiences of being a lab head', believes Joseph.

There's a strong focus on understanding the genetic risk of disease at an individual cell level, and the role the cellular microenvironment plays in supporting or suppressing these processes.

Single cell sequence data and technology is a key approach because of the phenomenal resolution it offers in identifying differences in the genomics of individual cells.

'We run a lot of single cell RNA, ATAC, and CITE-seq, mainly with the 10x Genomics Chromium platform, but also plate based assays.'

'We are also increasingly using spatial RNA sequencing with (10x Genomics) Visium,' he adds.  'It is a simple workflow and like their single cell assays, the protocols and supporting software are excellent. Spatial sequencing has solved the problem of trying to understand the genomics of cells within their original microenvironment, offering a lot of exciting possibilities.'

At the outset Joseph's group tried Drop-seq, built from spare lab equipment, and an early, plate-based adaptation using sorted ChemGene barcoded beads. Lack of reproducibility and robustness of these approaches was a concern, and they wanted a system that was more tightly controlled. Moving on to an inherited Fluidigm C1 system provided high-quality data but was low throughout and high cost per cell.

2-mon.jpgThe 10x Chromium launched just as Joseph was awarded an equipment grant, so became a logical choice based on the types of experiments they wanted to conduct.

As Joseph relates: 'I had spent a lot of time as a postdoc working on understanding and correcting batch effects in bulk RNA-seq or microarray data. With these data types, in some instances, the 'run' accounted for 30% of the total variance. When I got my first 10x Chromium Controller, there were almost no papers, and none on batch effects published. So, to be honest, I was expecting massive variation in RNA-seq levels based on chip or lane position.

I was incredibly surprised, and impressed, when our initial experiments revalued batch effects at <2% variance. This is a remarkable achievement, and in my opinion has been somewhat overlooked.'

In 2019 the GWCCG ran a total of 221 separate single cell projects, the majority using 10x Genomics technology. In almost every instance, data quality was excellent and feedback from researchers positive.

When prompted, Joseph nominates a large population-scale project involving scRNA-seq data on greater than 1,000 people as their most exciting current project - a huge undertaking, he reflects.

Going forward, he's keen to explore the new Chromium Single Cell Multiome ATAC + Gene Expression assay, gaining deeper insight into single cell characterisation.

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