New on the singles scene
CAMBRIDGE, Mass.—With a goal of accelerating the development of research methods and discoveries in mammalian single-cell genomics, the Broad Institute and South San Francisco-based Fluidigm Corp. announced May 21 the launch of a new research center.
The Single-Cell Genomics Center (SCGC) will be housed at the Broad Institute’s campus in Massachusetts and will feature a complete suite of Fluidigm single-cell tools, protocols and technologies, most notably the BioMark HD System. The center is also expected to act as a hub for collaboration among single-cell genomics researchers in such areas as stem cells and cancer biology.
The idea for the center grew out of ongoing collaborations between the Broad Institute and Fluidigm that involve multiple genomic platforms. More than that, though, “the creation of the SCGC at the Broad Institute is one of the latest announcements regarding Fluidigm and single-cell research, but is part of a progression of activities in this area that have contributed to the rapid growth of single-cell research over the past few years,” Howard High, director of corporate communications at Fluidigm, tells ddn. “Among those steps was the adoption of Fluidigm technology by thought leaders in single-cell research and their ability to publish numerous provocative, single-cell, peer-reviewed papers; then the acceptance of Fluidigm technology to conduct single-cell research by a broader researchers; and then late last year NIH and other funding bodies allocating funds specially targeted for single-cell research.”
The idea of heterogeneity among cells in tissue samples and other populations in not a new revelation for researchers, but this cellular variability is masked by averaging data across pooled cell samples, the Broad and Fluidigm note. They explain that the ability to tease out single-cell genomic data has historically been limited by a lack of standardized, user-friendly methods that would allow the broader biological and clinical communities to study individual cellular variability at high definition, high throughput and low cost.
Advances in technology such as Fluidigm’s microfluidic chips and high-throughput instruments have made single-cell studies feasible by converting cellular heterogeneity from a source of background noise to “a source of information enabling cutting-edge discoveries.”
“With the Single-Cell Genomics Center, we will enable researchers to access the exciting new world of single-cell genomics, catalyze discoveries and advance our understanding of this important area of biology,” said Dr. Wendy Winckler, director of the Genetic Analysis Platform at the Broad Institute, in the news release about the collaboration.
Fluidigm’s technology reportedly provides the capabilities required to analyze single cells—such as microfluidics and sensitivity at the nanoscale level—as well as parallel processing of a large number of cells and interrogation of a large number of gene targets.
“The cell is the fundamental unit of life, and through greater understanding of it, researchers can make breakthroughs in large and important fields, such as cancer diagnosis and therapy, stem cell biology, vaccine development and even the mounting battle against drug-resistant bacteria. We expect this center to inspire, enable and accelerate efforts in the emerging field of single-cell research,” said Gajus Worthington, president and CEO of Fluidigm, in an official statement.
Taking a single-cell genomics route can quickly lead to the need to run tens of thousands of samples, and Fluidigm’s chips can run approximately 10,000 experiments in parallel at a time, High points out.
“Especially for single-cell research, Fluidigm technology is the only one available today that can deliver the sensitivity you need at the single-cell level, with the high throughput that allows you to process huge numbers of cells, and run many complex tests that allow you to study many genes,” High maintains. “So we had the right technology, and as for pairing with the Broad—well, it’s the Broad, which is one of the premier biological research organizations in the world. For Fluidigm, it was a great opportunity to work with a great organization.”
High notes that the Broad is dedicating scientists, equipment and facilities to the SCGC, but Fluidigm has also placed one of its senior scientists, Dr. Ken Livak, at the institute to oversee the SCGC.
Through this collaborative effort, the researchers at the SCGC intend to develop novel single-cell, microfluidic approaches for gene expression profiling, RNA/DNA sequencing and epigenetic analysis. The goal of these efforts is to make single-cell research accessible to the greater scientific community by developing and disseminating new workflows, reagents, bioinformatics tools and data sets.
In the end, the Broad and Fluidigm expect that these advances will allow deeper exploration of the underlying causes of many diseases, including the progression of individual cancers, differential immune responses and the maturation of stem cells.
“Our intent is to establish the center as a focal point to enhance collaboration and accelerate the science, applications, methods and discoveries in single-cell genomics research,” said Livak, Fluidigm’s senior scientific fellow, who will act as the alliance manager at the Broad Institute, overseeing research projects amongst the center and project partners. “Our efforts with the Broad Institute in forming a center that specifically focuses on single-cell research represent a big step forward for this emerging area of biological research.”
Broad Institute study provides new clues about cancer cell metabolism
CAMBRIDGE, Mass.—In a study recently published in the journal Science, researchers from the Broad Institute and Massachusetts General Hospital (MGH) looked across 60 well-studied cancer cell lines, analyzing which of more than 200 metabolites were consumed or released by the fastest-dividing cells, yielding the first large-scale atlas of cancer metabolism. According to the researchers, their work also points to a key role for the smallest amino acid, glycine, in cancer cell proliferation.
Senior author Vamsi Mootha, co-director of the Broad Institute’s Metabolism Program and a professor at Harvard Medical School and MGH, and his colleagues developed a technique known as CORE (COnsumption and RElease) profiling, which allowed them to measure the flux of metabolites—the precursors and products of chemical reactions taking place in the body. The team applied CORE profiling to the NCI-60, a collection of 60 cancer cell lines that have been studied by the scientific community for many decades. Data about drug sensitivity, the activity of genes and proteins, rates of cell division and much more are publicly available for these cell lines, which represent nine tumor types. The team’s compendium of information about metabolites has also been made publicly available.
“Using CORE, we can quantitatively determine exactly how much of every metabolite is being consumed or released on a per-cell, per-hour basis,” says co-first author Mohit Jain, a postdoctoral fellow in the Mootha laboratory. “We can now start to derive flux or transport of nutrients into or out of the cell.”
One of the most striking results of the new data is how the pattern of glycine consumption relates to the speed of cancer-cell division. In the slowest-dividing cells, small amounts of glycine are released into the culture media. But in cancer cells that are rapidly dividing, glycine is rapaciously consumed. The researchers note that very few metabolites have this unusual pattern of “crossing the zero line,” meaning that rapidly dividing cancer cells consume the metabolite while slowly dividing cells actually release it.
In addition to looking for metabolites that correlated with rates of cell division, the team also looked at the expression of almost 1,500 metabolic enzymes. Enzymes required for biosynthesis of glycine within the mitochondria were among the most highly correlated.
“We have two independent methods—metabolite profiling as well as gene expression profiling—both of which point to glycine metabolism as being important for rate of proliferation,” says Mootha.
“This method offers a way of getting a quick overview of a particular cell type or tissue, allowing you to see what a cell requires to survive or grow,” says Nilsson. “We’re interested in applying this in other settings, to liver cells and muscle tissue and to study conditions such as diabetes. There are lots of potential applications.”