Single Cell Accelerator projects in the technology innovation lab

19 September 2018
Despite being launched just a few short months ago, there are several collaborative projects already in
progress with the potential to revolutionize scientific understanding of biological and pathological processes by offering brand-new, high-resolution insights.

Akoya Biosciences gives new powers to traditional tech 
Akoya Biosciences (US) has developed an innovative technology to enable spatially-resolved quantitative
tissue phenotyping at the cellular and subcellular level. The CODEXTM technology (CO-Detection by indexing) transforms traditional fluorescent microscopes into powerful high-dimensional tissue imaging stations that can analyze tissue architecture and heterogeneity through multiplex staining. Characterizing the interaction of single cells and their corresponding microenvironments is of major interest to VIB and is also one of the key goals of the Single Cell Accelerator program.

Impact research in VIB's domains 
“This platform is clearly the next step in single cell research,” confirms Martin Guilliams (VIB-UGent Inflammation Research Center). “The ability to accurately map distinct subsets of single cells in
tissues such as the liver will certainly drive the Human Cell Atlas forward!” The possibility of detecting up to 50 protein markers in a single tissue section opens new research avenues. Gabriele Bergers (VIB-KU Leuven Center for Cancer Biology): “The Akoya system is an impressive platform that enables my group to evaluate up to​ 30 different cell types simultaneously in tumor niches. In addition, it validates our spatial transcriptomics analysis and pins down protein expression to the single-cell level.”

Wai Long Tam (life science technology specialist at the Technology Innovation Lab and Akoya project leader), is working alongside multiple VIB groups in both Ghent and Leuven. “Characterizing the interactions of single cells and their corresponding microenvironments is one of the key goals of the SCA,” he affirms, “and the CODEX platform has quickly brought novel insights into both normal biological and disease processes.”

For this project, Wai is collaborating closely with Saskia Lippens, Manager Bio-Imaging Core, adding that “Together with the Technology Innovation Lab, and research groups that are willing to invest in early stages of technology-testing, we can explore future applications in the imaging field. This allows us to get acquainted with new emerging techniques, test these and adapt them to the needs of the VIB research questions. Multiplex staining combined with spatial information is very powerful and through the Technology Innovation Lab initiative we can evaluate whether the CODEX technique is suited to become part of our future portfolio.”

Mission Bio Revolutionizes SNV identification and streamlines genome editing 
The Tapestri platform from Mission Bio (US) uses microfluidics to identify approximately 300 single-nucleotide variants (SNVs) and indels at the DNA level, in up to 10,000 cells per run. In this technology, single cells are encapsulated with proteases in droplets, resulting in the release of DNA. Barcoded beads with PCR reagents mix are subsequently added, and the amplicons of interest amplified by PCR. The generated sequencing libraries are then pooled and sequenced by NGS, allowing SNP profiling at the single-cell level.
VIB will be one of the first European institutes to have the Tapestri platform, which will be placed in the Technology Innovation Lab in the VIB-KU Leuven Center for Cancer Biology. Pre-made and custom panels will be evaluated for the selected projects. Next to its importance in multiple precision medicine applications, the Tapestri system will also be highly useful in performing quality control of CRISPR genome editing of on-target and off-target events.

RNA-seq enhanced by single-cell surface protein profiling 
Multiple high-impact papers have been released in the last few months that demonstrate the importance of single cell RNA-seq in a wide range of medical applications. Correlation with protein levels at a similar resolution was previously lacking. Three different groups recently developed a breakthrough technology in parallel using oligo-tagged antibodies, which enable surface protein profiling and RNA-seq at the single cell level (Shahi et al., Scientific Reports 2017 – Stoeckius et al., Nature Methods 2017 – Peterson et al., Nature Biotechnology 2017).

In this method, single-cell suspensions are incubated with antibodies conjugated to a barcoded, poly-adenylated oligo tag. Unbound antibodies are subsequently washed away, after which the cells are prepared for a single-cell RNA-seq experiment. Since the antibodies are barcoded, the downstream NGS results provide epitope profiles alongside single-cell RNA-seq data. Multiple VIB groups across different centers have expressed their interest in this extremely powerful technology.

Over the coming months, VIB will work towards setting up established protocols for this technology. “We really want to boost the uptake of this technology at VIB. For this, we will collaborate closely with BioLegend on their commercialized conjugated antibodies, while we will also explore different in-house routes of oligo-tagging of antibodies and other affinity reagents,” says Silvie Van den Hoecke, life science technology specialist at Tech Watch.

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 'Single Cell at ​​VIB'