Genomics became a household word in the 90's. Now it's
time for proteomics. This complex and dynamic field focuses on the proteome,
the set of all proteins derived from the genome. Interest in this relatively
new field is growing rapidly, providing innumerable research opportunities for
investigators around the world. A recent infusion of funds from the NIH will
substantially increase those opportunities for researchers in Kansas. In
October 2002, the University of Kansas received a five-year, $10.2 million
COBRE grant from the National Institutes of Health to conduct research in
proteomics and protein structure and function.
COBRE is an acronym for Center of Biomedical Research Excellence.
Assistant Professor of Chemistry, KU
According to COBRE Project Leader and Medicinal Chemistry
Professor Bob Hanzlik, different researchers define proteomics differently,
but generally all agree that it involves the identification and characterization
of the individual proteins in living cells. This sounds relatively simple, but
in actual practice, just identifying all the individual proteins present in a
biological sample is a huge undertaking. Some of the complexity comes from the
fact that unlike the genetic information of the cell, which is carefully
preserved during the life of a cell, and faithfully copied and handed down during
cell division, different proteins are constantly coming and going or being
modified throughout the life of a cell.
Every cell in the body has exactly the same
genome, but not every gene is expressed all the time. Many proteins are only
made at specific times during the life of a cell and different types of cells
are different because they express different proteins, different subsets of
the genome. Liver cells differ from muscle cells or brain cells, because they
make different proteins having different structures and functions. Likewise,
tumor cells and diseased cells express some different proteins from normal
cells. The fact that protein structures also change in various ways during the
life of a cell further complicates things. For example, as proteins age they
sometimes deteriorate, creating further structural variation. Proteins are also
altered chemically in response to sunlight, oxygen, free radicals, and other
reactive chemicals that may be part of the diet or inhaled as pollutants.
Another dimension of proteomics that further
complicates the field is that in addition to outside influences, the proteins
themselves can change each other's structure and function. The normal function of some proteins can be switched off and on, back and forth,
by modifications to their chemical structure that are brought about by other
proteins. This process often operates in a cascade-like fashion from one
protein to the next, relaying information vital to the control of cell
functions such as contraction or secretion and creating web-like networks of
interactions. A significant but exciting challenge in proteomics is to
determine for a given protein which protein partners it interacts with in the
overall functioning of the cell.
"Proteomics is not unlike studying the complex
interactions between a large number of individuals in a society," said
Hanzlik. "No one person relates to everyone, but there
are plenty of cross-interactions that are constantly changing. It's like that
with the proteome. Most proteins have at least a few partners, while some have
many. Finding all the individual proteins is a huge job, but then working out
all the interactions that make a cell alive--rather than just a dead bag of
chemicals--is a daunting challenge but an essential one."
The COBRE grant awarded to KU will fund research into the
interactions of proteins with the other important constituents of cells
including DNA, other proteins, and small molecules. The grant, whose formal
title is "Protein Structure and Function," will fund the work of six
junior faculty researchers, each of whom is studying one or more specific proteins
from a multitude of viewpoints.
In light of the huge amount of proteomics research going
on worldwide, Hanzlik says this COBRE grant represent a significant leap forward
for the state of Kansas. "These funds will help our researchers stay ahead
of the curve, which strategically is the place to be. We need to bring an
awareness of that to biologists and clinicians across the state and around our
region, and convince them that they could accelerate certain aspects of their
own research enormously by partnering with us. Clinicians know what the
critical biological problems are, and we have the technical ability to solve
these problems through studies of protein structure and function and the
techniques of proteomics. These are the kinds of partnerships were actively
seeking, those likely to bring a more direct payout in terms of increased understanding
of basic biochemistry, disease mechanisms and diagnostics."