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Broad Institute and Fluidigm launch new research center to focus on mammalian single-cell genomics

Jeffrey Bouley
CAMBRIDGE, Mass.—With a goal of accelerating the developmentof research methods and discoveries in mammalian single-cell genomics, theBroad Institute and South San Francisco-based Fluidigm Corp. announced May 21the launch of a new research center.
The Single-Cell Genomics Center (SCGC) will be housed at theBroad Institute's campus in Massachusetts and will feature a complete suite ofFluidigm single-cell tools, protocols and technologies, most notably theBioMark HD System. The center is also expected to act as a hub forcollaboration among single-cell genomics researchers in such areas as stemcells and cancer biology.
The idea for the center grew out of ongoing collaborationsbetween the Broad Institute and Fluidigm that involve multiple genomicplatforms. More than that, though, "the creation of the SCGC at the BroadInstitute is one of the latest announcements regarding Fluidigm and single-cellresearch, but is part of a progression of activities in this area that havecontributed to the rapid growth of single-cell research over the past fewyears," Howard High, director of corporate communications at Fluidigm, tells ddn. "Among those steps was the adoption of Fluidigmtechnology by thought leaders in single-cell research and their ability topublish numerous provocative, single-cell, peer-reviewed papers; then theacceptance of Fluidigm technology to conduct single-cell research by a broaderresearchers; and then late last year NIH and other funding bodies allocatingfunds specially targeted for single-cell research."
The idea of heterogeneity among cells in tissue samples andother populations in not a new revelation for researchers, but this cellularvariability is masked by averaging data across pooled cell samples, the Broadand Fluidigm note. They explain that the ability to tease out single-cellgenomic data has historically been limited by a lack of standardized, user-friendlymethods that would allow the broader biological and clinical communities tostudy individual cellular variability at high definition, high throughput andlow cost.Advances in technology such as Fluidigm's microfluidic chipsand high-throughput instruments have made single-cell studies feasible byconverting cellular heterogeneity from a source of background noise to "asource of information enabling cutting-edge discoveries."
"With the Single-Cell Genomics Center, we will enableresearchers to access the exciting new world of single-cell genomics, catalyzediscoveries and advance our understanding of this important area of biology,"said Dr. Wendy Winckler, director of the Genetic Analysis Platform at the BroadInstitute, in the news release about the collaboration.
Fluidigm's technology reportedly provides the capabilitiesrequired to analyze single cells—such as microfluidics and sensitivity at thenanoscale level—as well as parallel processing of a large number of cells andinterrogation of a large number of gene targets.
"The cell is the fundamental unit of life, and throughgreater understanding of it, researchers can make breakthroughs in large andimportant fields, such as cancer diagnosis and therapy, stem cell biology,vaccine development and even the mounting battle against drug-resistantbacteria. We expect this center to inspire, enable and accelerate efforts inthe emerging field of single-cell research," said Gajus Worthington, presidentand CEO of Fluidigm, in an official statement.
Taking a single-cell genomics route can quickly lead to theneed to run tens of thousands of samples, and Fluidigm's chips can runapproximately 10,000 experiments in parallel at a time, High points out.
"Especially for single-cell research, Fluidigm technology isthe only one available today that can deliver the sensitivity you need at thesingle-cell level, with the high throughput that allows you to process hugenumbers of cells, and run many complex tests that allow you to study manygenes," High maintains. "So we had the right technology, and as for pairingwith the Broad—well, it's the Broad, which is one of the premier biologicalresearch organizations in the world. For Fluidigm, it was a great opportunityto 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 itssenior scientists, Dr. Ken Livak, at the institute to oversee the SCGC.
Through this collaborative effort, the researchers at theSCGC intend to develop novel single-cell, microfluidic approaches for geneexpression profiling, RNA/DNA sequencing and epigenetic analysis. The goal ofthese efforts is to make single-cell research accessible to the greaterscientific community by developing and disseminating new workflows, reagents,bioinformatics tools and data sets.
In the end, the Broad and Fluidigm expect that theseadvances will allow deeper exploration of the underlying causes of manydiseases, including the progression of individual cancers, differential immuneresponses and the maturation of stem cells.
"Our intent is to establish the center as a focal point toenhance collaboration and accelerate the science, applications, methods anddiscoveries in single-cell genomics research," said Livak, Fluidigm's seniorscientific fellow, who will act as the alliance manager at the Broad Institute,overseeing research projects amongst the center and project partners. "Ourefforts with the Broad Institute in forming a center that specifically focuseson single-cell research represent a big step forward for this emerging area ofbiological research."

Broad Institute study provides new clues about cancercell metabolism
CAMBRIDGE, Mass.—In a study recently published in thejournal Science, researchers from theBroad Institute and Massachusetts General Hospital (MGH) looked across 60well-studied cancer cell lines, analyzing which of more than 200 metaboliteswere consumed or released by the fastest-dividing cells, yielding the firstlarge-scale atlas of cancer metabolism. According to the researchers, theirwork also points to a key role for the smallest amino acid, glycine, in cancercell proliferation.
Senior author Vamsi Mootha, co-director of the BroadInstitute's Metabolism Program and a professor at Harvard Medical School andMGH, and his colleagues developed a technique known as CORE (COnsumption andRElease) profiling, which allowed them to measure the flux of metabolites—theprecursors and products of chemical reactions taking place in the body. Theteam applied CORE profiling to the NCI-60, a collection of 60 cancer cell linesthat have been studied by the scientific community for many decades. Data aboutdrug sensitivity, the activity of genes and proteins, rates of cell divisionand much more are publicly available for these cell lines, which represent ninetumor types. The team's compendium of information about metabolites has alsobeen made publicly available.
"Using CORE, we can quantitatively determine exactly howmuch of every metabolite is being consumed or released on a per-cell, per-hourbasis," says co-first author Mohit Jain, a postdoctoral fellow in the Moothalaboratory. "We can now start to derive flux or transport of nutrients into orout of the cell."
One of the most striking results of the new data is how thepattern of glycine consumption relates to the speed of cancer-cell division. Inthe slowest-dividing cells, small amounts of glycine are released into theculture media. But in cancer cells that are rapidly dividing, glycine israpaciously consumed. The researchers note that very few metabolites have thisunusual pattern of "crossing the zero line," meaning that rapidly dividingcancer cells consume the metabolite while slowly dividing cells actuallyrelease it.
In addition to looking for metabolites that correlated withrates of cell division, the team also looked at the expression of almost 1,500metabolic enzymes. Enzymes required for biosynthesis of glycine within themitochondria were among the most highly correlated.
"We have two independent methods—metabolite profiling aswell as gene expression profiling—both of which point to glycine metabolism asbeing important for rate of proliferation," says Mootha.
"This method offers a way of getting a quick overview of aparticular cell type or tissue, allowing you to see what a cell requires tosurvive or grow," says Nilsson. "We're interested in applying this in othersettings, to liver cells and muscle tissue and to study conditions such asdiabetes. There are lots of potential applications."
Funding for the work came from the National Institutes ofHealth and the Nestle Research Center.

Jeffrey Bouley

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