Protein World Atlas
If DNA is the blueprint of biology, then proteins are the general
contractors, workers, power tools and half of the building
materials. Yet the methods for studying proteins remain cumbersome
even as genomic tools become faster and more powerful.
A team of scientists from Sweden aim to fill that gap with an
ambitious project: a high-throughput, antibody-based portrait of the
human proteome (the set of all proteins made by human beings). The
first fruit of their labor is the freely available Human Protein
Atlas, initially released in August 2005, which describes the
location and quantity of about 700 proteins in 48 tissues and 20
types of cancer. The project, led by Mathias Uhlén and based
at the Royal Institute of Technology in Stockholm and Uppsala
University, is planned eventually to include nearly every human protein.
The atlas (www.proteinatlas.org) consists of
photomicrographs made with a technique called immunohistochemistry,
in which an antibody labels its target, or epitope, on a thin slice
of tissue (or in this case, a "tissue microarray" of up to
1,000 samples at a time). This method pinpoints the protein to a
specific compartment of a specific cell in a specific tissue. More
than 500 high-resolution, high-magnification images are available
for each antibody.
Most of the antibodies are generated from PrESTs, or protein epitope
signature tags, that are made in vitro from predicted
coding regions in the human genome. The purified
"monospecific" antibodies are rigorously screened for
sensitivity and selectivity. Some PrESTs correspond to well-studied
genes, including ones implicated in cancer and other diseases. But
others are more mysterious, representing genes that have never been investigated.
For example, the unnamed gene NP_443138.1 on chromosome 22 encodes a
protein with unknown function and no clear relatives in other
species, but its pattern of distribution is fascinating. Above right
is the standard summary of staining intensity for this protein in
various tissues and tumors. Red indicates the highest concentration
of the protein, and orange and yellow signify lesser amounts. White
shows a negative result; black denotes missing images. A small
sample of the stained tissue sections is shown at left, in which
brown marks the presence of the NP_443138.1 protein and blue is a
general stain used to see the surrounding tissue. The protein is
found in (from left to right) Purkinje cells in the
cerebellum, skeletal muscle fibers, the outer layer of skin and
subpopulations of tumor cells in cancers of the head and neck.
Describing protein location is only the first step. The project's
eventual goal is to use the antibodies as tools to explore the
structures, functions and interactions of proteins. Skål!