Center for Causal Consequences of Variation (CCV)
CCV
supports the NHGRI Strategic Plan
In
February 2011, the National Human Genome
Research Institute (NHGRI) published a
Strategic Plan for translating the
advances made in genomic science since the Human Genome Project (HGP) into improved methods and
practices for diagnosis and treatment of human diseases. CCV research directly supports two key
objectives developed in the Strategic Plan:
Understanding the Biology of Genomes and Understanding the Biology of Disease:
·
By developing
methods that directly analyze the causality
between human genetic variation and phenotype, the CCV will help take the
catalogs of human variation and disease associations that have been collected
since the HGP to the next logical
step by providing generally applicable experimental methods for distinguishing
which variations make real differences to biology vs. which are incidental to it.
·
These CCV methods
will apply to non-coding as well as
coding variations in the human genome, a key need identified in the Strategic Plan because there is vastly
more variation in non-coding vs. coding DNA in humans and it is much more
difficult to understand. The methods
will also be applicable to newly
discovered and rare variations,
such as those being identified by the 1000
Genomes Project and other genome and exome sequencing efforts (e.g., PubMed).
·
CCV’s aim of
extending these methods to induced
Pluripotent Stem Cells and cell types that can be derived from them will
provide a way of understanding the ways in which the causality of variations
may operate differently in different human cell types or tissues. This again promises to take catalogs of human
variation and disease associations to a next logical step, as these catalogs
usually offer only limited abilities to analyze the impact of variations on
different cell types.
·
Similarly,
CCV-developed methods for highly parallel in
situ single-cell RNA transcription analysis will enable single cell
resolution of different behaviors of cells in complex tissues or cell
populations. Since non-coding variations
are generally conceived to influence transcription patterns, highly parallel
single cell transcription analysis will provide ways of tracking the impacts of
different combinations of non-coding variations, or of non-coding variations in
multiple cell types, in single experiments.
In addition to supporting the two strategic objectives
of Understanding the Biology of Genomes and Disease, CCV research also contributes
to other elements of the Strategic Plan,
including:
·
All of the CCV’s
technology development efforts focus on developing methods that will work with
high efficiency, can be run in highly parallel manners, and which will work
with small samples and small amounts of reagents. As these features all contribute to lowering
the economic costs of applying these methods, these features will support their
translation into clinical practice where the scale-up costs of using new
technology can be a critical barrier.
·
By developing
methods for routinely engineering changes to the genomes of human induced
Pluripotent Stem Cells, will provide tools that will have direct
application to Gene
Therapy and will thus contribute to development of new therapeutics.
CCV supports NHGRI CEGS program
objectives
Centers for Excellence in Genomics
Sciences (CEGS) are a class of Centers funded by the NHGRI to develop
potentially game-changing capabilities that could change the course of
biological research. CEGS bring together
multi-investigator, multi-disciplinary teams to work out novel approaches to
biological and technological problems, or to generate and analyze new forms of
‘omics’-level biological data, that will enable researchers to overcome
barriers to understanding and control of biology critical to improving human
health and reducing the burden of disease.
CEGS are expected to explore approaches that are high-risk but have high
potential, and, while they focus on specific important biological problem
areas, are expected to develop methods that can be generally applied to other
biological problems. CEGS must deliver
innovative research products that could not have been achieved without the
ability to pursue high-risk, multi-disciplinary science provided by the CEGS
program. The CCV meets these CEGS critera in the following ways:
·
As described
above, the CCV addresses a critical need for general methods for engineering human
genomes in ways that can be used to analyze the causal consequences of human
genetic variations in many human cell types.
These methods will overcome present-day limits to understanding and
applying the wealth of information on human variation collected by genome
sequencing and Genome Wide
Association Studies.
·
The CCV brings
together researchers with proven track records in genetic engineering, stem
cell technology and biology, and development of high-throughput ‘omics’ methods
and automation, with the goal of developing genome engineering methods that can
be applied generally, inexpensively, and, ultimately, routinely throughout biology and
medicine. While many labs and companies
have developed methods for modifying genetic loci, the engineering of human
cells remains a difficult problem characterized by low efficiencies and
cumbersome, biology-specific screening and selection systems. By setting itself the higher target of
developing general, high-efficiency, and highly parallelizable methods, the CCV
explores high-risk, high-potential approaches that could not be pursued outside
of a CEGS.
In addition to these scientific criteria for a CEGS,
the CCV also meets CEGS’ commitments to increasing the representation of
underrepresented minority communities in genomics sciences careers by
maintaining a diversity program.
Last modified: 1/31/2012 11:41 AM by John Aach