Broad Institute awarded major grant to bolster epigenomics research

Researchers at the Broad Institute of Harvard and MIT announced today that they have received a grant from the National Institutes of Health (NIH) to map the epigenomes of a variety
of medically important cell types, including human embryonic stem cells.
The five-year, ~$15M grant, part of the NIH Roadmap for Medical
Research, designates the institute as one of four Reference Epigenome
Mapping Centers nationwide that will aim to transform the understanding
of an exquisite control system — a code of so-called “epigenetic” cues
that specify when and where in the body genes are made active. To
systematically decipher and analyze these controls, researchers from
across the Harvard and MIT communities will come together to study at
least 100 distinct types of human cells using the latest methods in stem
cell biology, genomics, technology, computation, and production-scale
research.

“The human epigenome is arguably the next frontier of genomic research,”
said co-principal investigator Alex Meissner, who is an associate member
at the Broad Institute and an assistant professor in the Department of
Stem Cell and Regenerative Biology at Harvard University. “Bolstered by
recent technological advances, this award will enable us to create
comprehensive epigenomic maps of a variety of human cells and to share
that data with the worldwide scientific community.”

“Epigenomics lies at a key intersection point between genome biology and
human disease,” said Bradley Bernstein, a co-principal investigator as
well as a Broad Institute associate member and an assistant professor at
Harvard Medical School and Massachusetts General Hospital. “By glimpsing
the normal epigenome at unprecedented breadth and depth, we will lay the
critical groundwork for future insights into the epigenetic basis of a
variety of diseases, including cancers.”

An overarching question in human biology is how cells in the body, with
the exact same DNA, adopt such distinct forms and functions. The answer
lies mainly in the epigenome, a special code of chemical tags affixed to
DNA or to its supporting proteins (known as “histones”) that act as
gatekeepers to the genome — enabling genes to be switched on or ensuring
they remain switched off. In the past few years, two techniques have
transformed researchers' abilities to probe cells' epigenomes: ChIP-Seq
and high-throughput bisulfite sequencing (HTBS). These technologies can
help pinpoint the genomic locations of various types of chemical tags,
such as methyl groups, and thus chart the epigenome.

The Reference Epigenome Mapping Center (REMC) at the Broad Institute
will help create comprehensive, genome-scale maps of the epigenomes of a
variety of cells, including human embryonic stem cells, various adult
stem cells, and other key cell types. The researchers will survey both
the DNA backbone and its accompanying histone proteins for chemical
modifications using HTBS and ChIP-Seq respectively, which take advantage
of the increased throughput and decreased cost of next-generation DNA
sequencing, and provide unprecedented precision and genomic coverage.

Just as the Human Genome Project provided researchers with a draft
genome sequence, the REMCs will help create draft epigenomic maps of a
diverse set of cell types. Those data will serve as a vast resource for
the scientific community to enhance the understanding of epigenetic
mechanisms of disease, pinpoint novel molecular targets for therapy,
complement ongoing investigations of the genetic susceptibilities of a
wide range of diseases, and bolster current research in stem cell
biology and regenerative medicine.

The NIH award to the Broad Institute represents one of four areas of
epigenomic research to receive funding under the NIH Roadmap Epigenomics
Program. In addition to the work of the epigenome mapping centers, other
funded centers will focus on epigenomics data analysis and coordination,
technology development in epigenetics, and the discovery of novel
chemical tags that mark the epigenomes of mammalian cells. Funds
totaling roughly $18 million will be awarded for these activities 2008.