|Fly and Worm Models to Teach Researchers About
Human Biology and Medicine
All Functional Elements to Be Targeted by
In an effort to understand every part of the genome needed for
organisms to develop and thrive, the National Human Genome Research
Institute, part of the National Institutes of Health, today announced
the first grants in a four-year, $57 million scientific mission
to identify all functional elements in the genomes of the fruit
fly and round worm.
The effort will build upon the foundation laid by the ENCyclopedia
Of DNA Elements (ENCODE) consortium, which is preparing to build
a comprehensive catalog, or “parts list,” of all elements in the
human genome crucial to biological function. In addition to genes
that code for proteins, these functional elements include: non-protein-coding
genes; regulatory elements involved in the control of gene transcription;
and DNA sequences that mediate the structure and dynamics of chromosomes.
“We are making great strides in identifying functional elements
in the human genome, but we still don’t know much about their biological
relevance. This parallel effort in the fruit fly and worm genomes
will provide us with information about the functional landscape
of two key model organisms, which should aid our efforts to tackle
such questions in humans,” said NHGRI Director Francis S. Collins,
Over the past several years, ENCODE researchers have collaborated
in a pilot project to develop and use innovative methods and technologies
to find functional elements in about 1 percent of the human genome.
The new effort, dubbed model organism ENCODE (modENCODE), will
take advantage of many of these methods and technologies. However,
rather than using the tools on the large and complex human genome,
researchers will apply them to the smaller, and therefore more
manageable, genomes of the fruit fly (Drosophila melanogaster)
and the round worm (Caenorhabditis elegans). The scientific
community relies heavily on these model organisms to identify common
genes, proteins and processes that underlie human medical conditions.
“One of the main reasons we were able to complete the Human Genome
Project ahead of schedule and under budget was that we learned
so much from sequencing the smaller genomes of model organisms,
such as the worm and fly. This work enabled us to perfect the high-throughput
methods and technologies that would be needed to completely analyze
the much larger sequence of the human genome,” said Robert H. Waterston,
M.D., Ph.D., chair of the Department of Genome Sciences, University
of Washington in Seattle, and one of the researchers receiving
a modENCODE grant.
The fruit fly and round worm modENCODE projects have been designed
so that similar elements in both organisms are being studied and
catalogued in parallel. Unlike ENCODE’s human-focused effort, modENCODE
researchers can also conduct experiments in flies or worms to validate
the biological relevance of the functional elements they identify.
By combining and comparing data from worm, fly and human, researchers
can learn far more about the functional elements than if they analyzed
the genome of just one organism.
“Both the fly and worm share many genetic similarities with humans,
yet their genomes are far easier to work with in experimental settings.
modENCODE will enable us to confirm what we’re finding in the human
genome by manipulating the fly and worm genomes in a precise and
rapid way,” said Elise Feingold, Ph.D., the NHGRI program director
in charge of the ENCODE and modENCODE projects. “If a DNA sequence
has been conserved throughout evolution — from worm to fly
to human — it is very likely that the sequence is functionally
The modENCODE research consortium is made up of teams of experts
who bring a great deal of knowledge about the biology of the fruit
fly and roundworm. Due to the complexity of the data, the teams
will work together to maximize the intellectual discussions and
quality of data analysis. The modENCODE grant recipients, the focus
of their research and their approximate funding levels are:
Susan Celniker, Ph.D., Lawrence Berkeley National
Laboratory, University of California at Berkeley — D.
melanogaster. “Comprehensive Characterization of the Drosophila
Transcriptome” — First-year funds, $3.6 million; total
funds, $14.5 million.
Steven Henikoff, Ph.D., Fred Hutchinson Cancer Research
Center, Seattle — C. elegans and D. melanogaster. “Genome-Wide
Profiling of Histone Variants in Drosophila and Caenorhabditis” — First-year
funds, $429,000; total funds, $7.4 million.
Gary Karpen, Ph.D., Lawrence Berkeley National Laboratory,
University of California at Berkeley. — D.
melanogaster. “Genome-Wide Mapping of Chromosomal Proteins
in Drosophila” — First -year funds, $1.8 million; total
funds, $7.2 million.
Eric Lai, Ph.D., Memorial Sloan-Kettering Cancer Center,
Sloan-Kettering Institute, New York. — D.
melanogaster. “Annotation of the Small RNA/microRNA Component
in the Drosophila Genome“ — First-year funds, $470,000;
total funds, $1.9 million.
Jason Lieb, Ph.D., The University of North Carolina
at Chapel Hill. — C. elegans. “Identification
of DNA Elements Governing Chromatin Function in C. elegans” — First-year
funds, $1.8 million; total funds, $9.1 million.
David MacAlpine, Ph.D., Duke University, Durham, N.C. — D.
melanogaster. “The Systematic Identification and Analysis
of Replication Origins in Drosophila” — First-year funds,
$469,000; total funds, $1.9 million.
Fabio Piano, Ph.D., New York University, New York. — C.
elegans. “Encyclopedia of C. elegans 3’UTRs and
Their Regulatory Elements” — First-year funds, $397,000;
total funds, $1.6 million.
Michael Snyder, Ph.D., Yale University, New Haven, Conn. — C.
elegans. “Global Identification of Transcription Factor
Binding Sites in C. elegans” — First-year funds,
$1.7 million; total funds, $6.6 million.
Robert Waterston, M.D., Ph.D., University of Washington,
Seattle. — C. elegans. “Global Identification
of Transcribed Elements in the C. elegans Genome” — First-year
funds, $1.4 million; total funds, $5.4 million.
Kevin White, Ph.D., University of Chicago. — D.
melanogaster. “A Cis Regulatory Map of the Drosophila
Genome” — First-year funds, $2.3 million; total funds,
In addition, NHGRI has awarded $1.3 million a year over four years
to establish the modENCODE Data Coordination Center, which will
be led by Lincoln Stein, M.D., Ph.D., Cold Spring Harbor Laboratory,
Cold Spring Harbor, N.Y. The Data Coordination Center will be the
main portal for the scientific community to retrieve the wealth
of data to be generated by these projects. NHGRI has designated
modENCODE project as a community resource project, which means
that all data generated for this project will be deposited in free,
public databases as soon as they are experimentally verified.
For more information about NHGRI’s ENCODE project, go to www.genome.gov/ENCODE.
NHGRI is one of 27 institutes and centers at the NIH, an agency
of the Department of Health and Human Services. The NHGRI Division
of Extramural Research supports grants for research and for training
and career development at sites nationwide. Additional information
about NHGRI can be found at its website, www.genome.gov.
The National Institutes of Health (NIH) — The Nation's
Medical Research Agency — includes 27 Institutes and
Centers and is a component of the U.S. Department of Health and
Human Services. It is the primary federal agency for conducting
and supporting basic, clinical and translational medical research,
and it investigates the causes, treatments, and cures for both
common and rare diseases. For more information about NIH and
its programs, visit www.nih.gov.