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Leading the Single Cell Revolution With Collaborative Research
droseyb [at] email.chop.edu (By Barbara Drosey)
Research in single cell biology has the potential to transform scientists’ understanding of biological processes by pinpointing cellular and molecular function at a much higher resolution than previously available.
A new Center of Emphasis at CHOP Research Institute — the Center for Single Cell Biology (CSCB) — aims to use the precision of single cell technology to take a deep look into the cellular path of multiple diseases, such as cancer, lung disease, neurological disease, and metabolic disease, to improve outcomes for pediatric patients.
“There is a scientific need to develop effective treatments and drug targets based on individual cell types,” said Kai Tan, PhD, who will lead the new Center with Co-Director Deanne Taylor, PhD. “The time is now for CHOP to position ourselves as a pediatric leader in this fast-evolving research area.”
Even at this relatively early stage of adoption, single cell technologies have advanced rapidly from single cell transcriptome analysis to single cell multi-omics profiling of DNA, chromatin, transcriptome, and proteome. Dr. Tan, an investigator in the Center for Childhood Cancer Research (CCCR) at CHOP and a professor of Pediatrics at the Perelman School of Medicine at the University of Pennsylvania, envisions combining these powerful assays to create comprehensive profiles of the same cell and its microenvironment that yield insights into the fundamental biology of disease processes.
Consider acute pulmonary disease as an example: The lung is comprised of 20 different cell types. Doctors know the medicines used to treat lung disease are effective, but they don’t fully understand how they work with particular cell types.
“What are the most effective cell type(s) to target for treatment?” Dr. Tan asked. “That's exactly what this kind of single cell technology can tell us and help us move toward our goal of precision medicine.”
Leveraging Technology, Data, and Talent
Dr. Tan expects the CSCB will make great strides in its first five years by establishing a core group of faculty members who will develop and use single cell technologies as a major approach in their basic and translational research. Dr. Taylor is also the director of Bioinformatics in the Department of Biomedical and Health Informatics at CHOP. She and her team will initially focus on the Center’s computational and analytical infrastructure for processing the diversity of single cell data to be generated by the Center, and recruiting new computational scientists as the Center grows.
“In addition to recruiting new faculty, we are excited to work with existing faculty, many of whom are interested in using this technology,” Dr. Tan said. “We cannot overstate the importance of educating our colleagues about these new technologies so they can leverage them in their own research.”
A fee-for-service Core under development will provide the CHOP research community with access to state-of-art single cell technologies. While CHOP currently has existing strains of experimental assays used in single cell research, the goal is to stay ahead of this rapidly developing scientific field.
“This Center will bring additional sequencing-based and imaging-based technologies utilized in the field of single cell biology,” Dr. Tan said. “CHOP has strength in the sequencing-based domain, and we would like to utilize the resources of the Center of Emphasis to bring expertise and technology to create a more robust imaging component.”
The CSCB will acquire equipment for high-throughput sequencing of the genomes of hundreds to thousands of cells, as well as new equipment for multiplexed and high-throughput imaging of RNA and protein in intact tissues.
Scientific Community Collaboration
Opportunities abound for collaboration among the CSCB and other programs across CHOP. The Center will develop clear and efficient protocols for tissue acquisition, in partnership with Biobanking and Pathology, to support availability of high quality single-cell-ready samples.
With the anticipated volumes of data generation, the Center will combine efforts with Arcus, an enterprise-wide effort to centralize CHOP data from all areas of clinical care and research, to create a single cell data repository that ranges from basic science data to omics and imaging data.
The Center is anticipated to act as an intellectual center for novel computational methods development by providing a fertile ground for collaboration between computational and wet lab faculty. The Center will also support the CHOP community by providing best-practice computational workflows and analytical tools for single cell and imaging research.
In addition, the CSCB will promote education and outreach through symposia, seminars, and other teaching opportunities to build CHOP scientists’ expertise in how to leverage single cell biology for research. Part of the Center’s mission is to train the next generation of junior faculty, postdocs, and graduate students to use these cutting-edge technologies to address their own research questions, and Dr. Tan anticipates extending this engagement to college and high school students.
“When developing the concept for the Center for Single Cell Biology, Dr. Taylor and I were not just thinking about scientific tools, but of creating an entity that will catalyze the effort to build a scientific community,” Dr. Tan said.
Foundation for the Future
Single cell biology already is yielding insights to enhance understanding of individual cells in the oncology field. Scientists are identifying mutations in the microenvironment of a tumor that cause malignancy, and then they track the evolution of the cancerous tumor at the cellular level in order to individualize therapies for subgroups of patients.
The new Center for Single Cell Biology will expand the work begun in 2018 by Dr. Tan and Co-principal Investigator Stephen Hunger, MD, chief of the Division of Oncology and director of the CCCR, to create the Center for Pediatric Tumor Cell Atlas. In April 2019, Dr. Taylor and Dr. Tan, along with CHOP and international colleagues who share an interest in promoting single cell approaches in pediatric research, published their support for the framework of the Pediatric Cell Atlas to characterize the cell type and states that define normal childhood development.
As part of a 10-center national consortium under the Moonshot grant for the Human Tumor Atlas, Drs. Tan and Hunger and their collaborators are leading the charge to identify targeted, single cell treatments for three subtypes of pediatric malignancy.
“The Moonshot grant provided a jumping point to build on our strengths and bring our research capacity to the entire Research Institute,” Dr. Tan said.