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To understand why cancer happens, you
have to look at cells, which is why scien-
tists want to know as much as possible
about cellular components and func-
tions. Since proteins do their job inside
cells, they are naturally considered to be
quite important.
The technique that scientists use to dis-
cover the secrets inside proteins is called
X-ray crystallography. Only a handful of
people in Norway have expertise in this
area, and most of them work in Tromsø.
Looking for a needle in the
haystack
Because there are so many different pro-
teins in a cell, you have to "break down"
the cell and "fish out" the one protein
you are looking for. This process is called
protein purification.
"As a rule, we can produce the proteins
we are looking for in bacteria, insect cells
or yeast. We produce these cells in large
tanks. Using human cells is in most cases
too time consuming and costly," says
Vibeke Os, of NorStruct.
After purification, the proteins are divi-
ded into tiny test tubes, to which are ad-
ded various salts, metals or solvents. The
fluid is steamed away, something which
makes the proteins "feel uncomfortable"
and causes them to agglomerate in a
specific pattern. The result is a pattern
that looks like a crystal.
All this work is very time consuming,
and there is no guarantee that the scien-
tists will be able to get crystals out of the
process. Often, they don't.
"It's like looking for needle in a haystack,
so it's great when we succeed. It feels
fantastic to create a perfect, diamond-
shaped crystal," says Os.
Bombarded by radiation
Although there is a lot of work involved
in creating crystals, the scientists are
literally left with just tiny amounts of
material to work with. A crystal of one
millimetre is considered to be large, and
usually they are much smaller.
To understand the information locked
inside the crystals, scientists bombard
the crystals with X-rays. The way in
which the X-rays are bent inside the
crystal says something about the atom's
position inside it. Atoms are the smallest
building blocks in biological substances.
And it is precisely this structure that the
researchers want to understand.
"We need to know how these large biolo-
gical molecules are built, atom by atom,
to see how they behave under certain
conditions. Once we understand this,
we perhaps add or remove portions of
the molecule in order to achieve effects
that originally were not possible. This is
how we can make improvements in the
protein, so that it will do what we want,"
says Os.
Curing disease
The structure of a molecule, such as
a protein, says a lot about how that
molecule works. This kind of knowledge
is crucial in both medicine and vaccine
development. Knowing what a disease-
causing molecule looks like could enable
us to "turn off " its activity, or increase
other activity. This could perhaps cure
the disease, or prevent a disease from
occurring, possibly allowing us to make
medicines that we see a need for, such as
birth control pills for men.
In other words, x-ray crystallography is a
powerful tool that has great significance
in scientific research.
"But not only just in the medicine," Os
says. "We can use this knowledge to
create agents with enhanced cleaning
properties, identify pollutants and break
down waste products, develop biofuels,
or for food production – like aiding in
the maturation of cheese or beer."
University of Tromsø –
Labyrint E/11
•••
33
Text: Randi M. Solhaug
Photo: NorStruct
It is very time consuming to create crystals from proteins.
In addition, there is no guarantee that the scientist will
succeed.
Scientists are looking for the atomic structures inside the
crystals. The structures reveal how the protein works.