KEY CORPORATE PLAYERS IN PROTEOMICS
Company
Location
Approach
Celera
Rockville, MD
Databases
Incyte Pharmaceuticals
Palo Alto, CA
Databases
GeneBio
Geneva, Switzerland
Databases
Proteome Inc.
Beverly, MA
Databases
PE Biosystems
Framingham, MA
Instrumentation
Ciphergen Biosystems
Palo Alto, CA
Protein arrays
Oxford GlycoSciences
Oxford, U.K.
2D gel/MS*
Protana
Odense, Denmark
2D gel/MS
Genomic Solutions
Ann Arbor, MI
2D gel/MS
Large Scale Proteomics Corp.
Rockville, MD
2D gel/MS
* 2D gel electrophoresis and mass spectrometry.
But Venter, never one to understate his ambitions, boasts: "We're going to
dominate in our own
way. We're going to have the biggest facility and the biggest database." He
concedes that the
huge amount of work needed to understand proteins and their interactions inside
cells guarantees
that many academic labs and other companies will also be players in the field.
But, he says, "we're
building a Celera-scale proteomics facility" capable of identifying up to 1 million
proteins a day.
Plans for the new facility are still coming together, Venter says, but it will likely
consist of a fleet of
up to 100 machines, including high-speed mass spectrometers for protein
analysis, as well as
additional protein separation devices. Celera also plans to boost the capacity of
its $100 million
supercomputer --which currently holds some 50 terabytes of genome data--by a
factor of 10 to
handle the expected torrent of protein data.
Venter will have Hunkapiller's help getting his operation up to speed. Last week,
PE--the parent
company of both Celera and PE Biosystems--announced that it will form a
proteomics research
center at its PE Biosystems site in Framingham, Massachusetts, to create new
high-speed
machines. As part of that initiative, PE officials plan to pursue two
technologies--one developed by
Denis Hochstrasser and colleagues at the University of Geneva in Switzerland,
the other by Ruedi
Aebersold at the University of Washington, Seattle--that aim to do for protein
analysis what the
high-speed gene sequencers did for genome work.
Outside observers say that with PE Biosystems' backing, Celera's move into
proteomics is likely
to be pivotal for the emerging field. "The genomics company stuck its flag in the
arena of
proteomics," says William Rich, president and CEO of Ciphergen, a proteomics
company based in
Palo Alto, California. "It sends a message to the protein people that the gene
people are not going
to sit around and wait" for proteomics companies to give them the information
they're looking for.
In fact, the march of genomics companies into proteomics is well under way.
Incyte
Pharmaceuticals, one of Celera's chief genomics rivals, is 2 years into an
extensive partnership
with Oxford GlycoSciences (OGS), a proteomics company based in Oxford,
England. OGS
creates protein profiles of different tissues in both healthy and diseased states,
and Incyte
incorporates this information into a proteome database that it markets to
pharmaceutical
companies. Incyte signed up its first subscriber to its proteomics database last
fall, giving it "a
significant lead over other companies in developing proteomics databases,"
asserts Incyte CEO
Roy Whitfield. And like Celera, the company is also flush with cash. Incyte
recently raised $620
million on the stock market, much of which is intended to bolster their proteomics
work, says
Whitfield.
Other companies are pushing into proteomics as well. Virtually every major
pharmaceutical
company has a proteomics effort under way, says Hanno Langen, who
directs proteomics
research at Hoffmann-La Roche in Basel, Switzerland.
Moreover, small proteomics firms, such as
Genomic Solutions of Ann Arbor, Michigan, and Large Scale Proteomics of
Rockville, Maryland,
are gearing up for initial public stock offerings to raise money for expanded
research. GNSL is PUBLIC NOW
That makes Celera a late entry into the field, and it has some catching up to do.
But it is betting
nearly $1 billion that it can close the gap.
The next step
This move toward understanding proteins has emerged from the increasing
recognition among
genomics and pharmaceutical researchers that identifying DNA, or even
messenger RNA
(mRNA)--the nucleotide messengers that signal cells to produce a particular
protein--is not enough.
Neither DNA nor mRNA can identify how much protein is produced inside a cell
or what it does
once created. Although researchers initially hoped that the presence of a large
amount of a
particular mRNA meant that copious quantities of the corresponding protein were
being produced,
"there is significant evidence that there is not necessarily a correlation between
mRNA levels and
protein levels," says Philip Andrews, a proteomics researcher at the University
of Michigan, Ann
Arbor. Other factors complicate the picture as well, he adds. For instance,
chemical modifications
such as phosphorylation play a key role in controlling protein activity; these
modifications cannot be
detected by screening nucleotides. "The genome tells you what could
theoretically happen" inside
the cell, explains Raj Parekh, the chief scientific officer at OGS. "Messenger
RNA tells you what
might happen, and the proteome tells you what is happening."
Figuring out what's happening at the protein level won't be easy even for Celera.
"Proteomics is a
much more difficult problem than genomics," says Andrews. Whereas the human
genome remains
largely unchanged among individuals, he explains, the expression of proteins
varies widely. Protein
expression changes dramatically from one tissue to another and even within
single tissues over
time as a person ages. What's more, thousands of chemical modifications occur
after proteins are
created that alter their enzymatic activity, binding ability, how long they remain
active, and so on.
Although there may be only some 100,000 human genes, the myriad of
modifications may give rise
to 10 million to 20 million chemically distinct proteins in a cell, says Andrews.
This complexity, Andrews and others say, makes it almost meaningless to
consider a human
proteome project--akin to the human genome project--to identify all proteins in
every tissue. The
best researchers can do is try to focus on changes in key proteins, such as
those involved in
disease and development. For that reason, skeptics argue that even with
Celera's deep pockets it
will not be able to sweep aside the competition. "I think it will be very hard for any
company to be
the dominant proteomics company, much more so than in genomics," says Mann
of Protana.
Venter agrees--in principle. But he adds that few competitors will be able to
match Celera's
industrial approach. "We'll be working through every tissue, organ, and cell," he
says.
Brute force
In the current proteomics rush, most companies are taking more or less the
same brute-force
approach to determining which proteins are present in various tissues, a
technique called
two-dimensional (2D) gel electrophoresis. Researchers start with a protein
extract from a tissue of
interest and then add it to a sheet of polymer Jell-O. By applying electric fields
across the length
and width of the sheet, they separate proteins by their electric charge and size.
The result is a
series of up to several thousand spots, each containing one or more types of
proteins.
Once segregated into separate spots and stained, the proteins are typically cut
from the gel one
by one, chopped into fragments with an enzyme called trypsin, and dried. Then
they are fed into a
mass spectrometer that weighs each fragment, forming what amounts to a mass
fingerprint of the
protein's fragments. From that fingerprint, researchers can work out the likely
combination of amino
acids comprising it and then compare that to a genomics database to identify the
corresponding
DNA sequence. With the DNA sequence in hand, they can get a clearer
identification of the protein.
Researchers can then monitor changes in the expression of that protein to see
whether it
correlates with a disease state or perhaps a drug response.
All of this takes time. Today's top-of-the-line 2D gel operations, complete with
robots to cut apart
the gels and computers to analyze the information, can study a couple of
thousand proteins a day.
As a result, it can still take months to figure out which proteins change their
expression in one set of
tissues.
Thursday June 29, 6:27 pm Eastern Time
Company Press Release
SOURCE: Genomic Solutions Inc.
New, Automated Proteomics Systems Installed
ANN ARBOR, Mich., June 29 /PRNewswire/ -- Genomic Solutions Inc. (Nasdaq: GNSL - news),
one of the world's leading suppliers of automated solutions for genomics and proteomics, today
announced the company will install two complete proteomics systems for new facilities at the
prestigious John Innes Centre (JIC) and the Institute of Food Research (IFR), both located in
Norwich, Norfolk, UK. The facilities are scheduled to open September 29, 2000.
These installations bring the total number of Genomic Solutions automated proteomic systems in
Europe to seven, with two in Germany and five in the UK. Merck Sharpe and Dohme, a major
pharmaceutical company, and the University of Aberdeen are among customers using the
Investigator(TM) Proteomic System.
``We chose Genomic Solutions to provide the proteomics instrumentation because we assessed
other suppliers and Genomic Solutions was the company that could provide the full specification
we wanted, when we wanted it,'' said Dr. Nick Walton, Senior Research Scientist, IFR, speaking
on behalf of both Institutes. ``It is also very important to us to have systems that both institutes
can use to interchange data with collaborators both on- and off- site. In addition, we felt confident
that Genomic Solutions would provide good, on-going application and service support for both
facilities,'' he noted.
Genomic Solutions Inc. designs, develops, manufactures, markets and sells instruments,
software, consumables and services used to determine the activity level of genes and to isolate,
identify and characterize proteins. The company's products and systems enable researchers to
perform complex, high volume experiments at a lower cost and in less time than traditional
techniques. As a result, Genomic Solutions products and systems facilitate more rapid and less
expensive drug discovery. Genomic Solutions markets products through its corporate
headquarters in Ann Arbor, Michigan USA, as well as offices in the United Kingdom and Japan.
Remaining worldwide distribution is provided by PerkinElmer Life Sciences through a strategic
alliance with Genomic Solutions. The two companies also cooperate to sell co-branded products
and collaborate to leverage their intellectual property and technologies.
JIC is a leading international center for research and training in plant and microbial science. It
generates and disseminates new knowledge, understanding and valuable intellectual property in
selected plants and microbes include plant pathogens. IFR is a premier international center for
independent, multi-disciplinary research in food safety, diet and health, food quality and consumer
sciences, including fundamental investigations of nutrient-gene interactions, the physiology and
molecular genetics of food pathogens and the physicochemical properties of food materials. The
proteomics facilities will enable both institutes to make full use of the data rapidly emerging from a
wide range of genome-sequencing projects to understand the factors which control and influence
gene expression at the protein level.
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