NOVEL TECHNOLOGY TO INVESTIGATE GENE ACTIVITIES AND MUTATIONS IN CANCER CELLS

Knowing how mutations in cancer cells work will help researchers better understand how they evolve to become resistant to drugs

Singapore – Scientists from the Agency for Science, Technology and Research’s (A*STAR) Genome Institute of Singapore (GIS), the National Cancer Centre Singapore (NCCS) and Fluidigm Corporation have developed a new technology to simultaneously and systematically investigate individual cancer cells within a tumour. The study was published in Clinical Chemistry on 7 December 2018.

It has been established that not every cancer cell in a tumour is alike (also known as clonal heterogeneity), and that mutations develop in the cells during the course of tumour growth. Some of these mutations can cause the tumour to evolve and develop resistance against therapy. To understand the complexity of this process, it is therefore often necessary to sequence the entire tumour.

However, there are limitations to existing technologies that illuminate the different components of a tumour, and how such mutations change its characteristics. In particular, it is technically challenging to simultaneously sequence a single cell’s DNA and analyse the activities of genes.

To address this problem, the team headed by Dr Axel Hillmer, Group Leader at GIS and senior author of this study, developed a novel technology termed COncurrent single cell RNA and TArgeted DNA sequencing (CORTAD-seq) – on an automated Fluidigm C1 microfluidic platform. CORTAD-seq allows researchers to test for the presence of mutations in single cells with high accuracy and take snapshots of the gene activities within those cells.

Dr Kong Say Li, Research Associate at GIS and lead author of this study, said, “CORTAD-seq is a tool which can be implemented easily by other researchers, and lead to more impactful discoveries. This method allows for insights into cancer evolution and clonal heterogeneity, the mechanisms of drug resistance towards targeted therapy, as well as the difference in gene activities of cancer and normal cells through the identification of cancer mutations.”

Dr Mark Lynch, Director of Single-Cell Genomics at Fluidigm, said, “Fluidigm is privileged to be partnered with GIS to develop CORTAD-seq, using microfluidics on the C1 system. This novel single-cell, multi-omic technology will help the characterisation of the tumour microenvironment at single-cell resolution and will thus help studies in cancer and immuno-oncology.”

Professor Ng Huck Hui, Executive Director at GIS, said, “We are delighted to be working with NCCS and Fluidigm Corporation to develop this novel technology. Such cross-boundary collaborations allow us to further our capabilities and break new frontiers in genomic science. Doing so will also help us better understand how cancer works, and will help bring about better healthcare outcomes for Singaporeans.”
IMAGES

Dr Kong Say Li and Dr Li Huipeng, the lead authors that developed CORTAD-seq on Fluidigm C1 microfluidic system, at Single Cell Omics Centre, Genome Institute of Singapore.

(Copyright: A*STAR’s Genome Institute of Singapore)
Notes to Editor:

The research findings described in this media release can be found in the scientific journal Clinical Chemistry, under the title, “Concurrent Single-Cell RNA and Targeted DNA Sequencing on an Automated Platform for Comeasurement of Genomic and Transcriptomic Signatures” by Say Li Kong^1,2†*, Huipeng Li^3†, Joyce A. Tai², Elise T. Courtois^3,4, Huay Mei Poh^1,2, Dawn Pingxi Lau⁵, Yu Xuan Haw², Narayanan Gopalakrishna Iyer⁵, Daniel Shao Weng Tan⁵, Shyam Prabhakar³, Dave Ruff^6,7, and Axel M. Hillmer^2,8*.

1. Translational Research, Genome Institute of Singapore, Singapore
2. Cancer Therapeutics and Stratified Oncology, Genome Institute of Singapore, Singapore
3. Computational and Systems Biology, Genome Institute of Singapore, Singapore
4. The Jackson Laboratory for Genomic Medicine, Farmington, CT
5. National Cancer Centre, Singapore
6. Fluidigm Corporation, South San Francisco, CA
7. Mission Bio, South San Francisco, CA
8. Institute for Pathology, University Hospital Cologne, Cologne, Germany.

† S.L. Kong and H. Li contributed equally to this work.

* Corresponding Authors: Kong Say Li (kongsl@gis.a-star.edu.sg) and Axel M. Hillmer (ahillmer@uni-koeln.de).
For media queries and clarifications, please contact:

Lyn Lai

Officer, Office of Corporate Communications

Genome Institute of Singapore, A*STAR

Tel: +65 6808 8258

Email: lai_yilin@gis.a-star.edu.sg

About A*STAR’s Genome Institute of Singapore (GIS)

The Genome Institute of Singapore (GIS) is an institute of the Agency for Science, Technology and Research (A*STAR). It has a global vision that seeks to use genomic sciences to achieve extraordinary improvements in human health and public prosperity. Established in 2000 as a centre for genomic discovery, the GIS will pursue the integration of technology, genetics and biology towards academic, economic and societal impact.

The key research areas at the GIS include Human Genetics, Infectious Diseases, Cancer Therapeutics and Stratified Oncology, Stem Cell and Regenerative Biology, Cancer Stem Cell Biology, Computational and Systems Biology, and Translational Research.

The genomics infrastructure at the GIS is utilised to train new scientific talent, to function as a bridge for academic and industrial research, and to explore scientific questions of high impact.

For more information about GIS, please visit www.gis.a-star.edu.sg.

About the Agency for Science, Technology and Research (A*STAR)

The Agency for Science, Technology and Research (A*STAR) is Singapore’s lead public sector agency that spearheads economic oriented research to advance scientific discovery and develop innovative technology. Through open innovation, we collaborate with our partners in both the public and private sectors to benefit society.

As a Science and Technology Organisation, A*STAR bridges the gap between academia and industry. Our research creates economic growth and jobs for Singapore, and enhances lives by contributing to societal benefits such as improving outcomes in healthcare, urban living, and sustainability.

We play a key role in nurturing and developing a diversity of talent and leaders in our Agency and research entities, the wider research community and industry. A*STAR’s R&D activities span biomedical sciences and physical sciences and engineering, with research entities primarily located in Biopolis and Fusionopolis. For ongoing news, visit www.a-star.edu.sg.

About Fluidigm

Fluidigm (NASDAQ:FLDM) develops, manufactures, and markets life science analytical and preparatory systems for markets such as mass cytometry, high-throughput genomics, and single cell genomics. We sell to leading academic institutions, clinical research laboratories, and pharmaceutical, biotechnology, and agricultural biotechnology companies worldwide. Our systems are based on proprietary microfluidics and multiparameter mass cytometry technology and are designed to significantly simplify experimental workflow, increase throughput, and reduce costs while providing excellent data quality. Fluidigm products are provided for Research Use Only. Not for use in diagnostic procedures.

We use our website (www.fluidigm.com), corporate Twitter account (@fluidigm), Facebook page (https://www.facebook.com/fluidigm), and LinkedIn page (https://www.linkedin.com/company/fluidigm-corporation) as channels of distribution of information about our products, our planned financial and other announcements, our attendance at upcoming investor and industry conferences, and other matters. Such information may be deemed material information, and we may use these channels to comply with our disclosure obligations under Regulation FD. Therefore, investors should monitor our website and our social media accounts in addition to following our press releases, SEC filings, public conference calls, and webcasts.

Fluidigm, the Fluidigm logo, and C1 are trademarks and/or registered trademarks of Fluidigm Corporation in the United States and/or other countries.