He [Maxon] clung to General Leger, holding on to him for dear life, his fingers digging into the back of his uniform. He was unabashedly crying, and I’d never heard such a painful sound. I hoped I never would again. “I can’t lose her. I don’t know….I don’t…”
(Image caption: The image of a cell’s DNA taken with the new super-resolution microscopy
technique developed at the Institute of Molecular Biology shows the DNA
in crisp detail (left). By contrast, a conventional microscopy image is
blurry, making it impossible to see the striking changes in DNA
discovered by the scientists at IMB (right). Credit: Aleksander Szczurek, Ina Kirmes)
Scientists at the Institute of Molecular Biology (IMB) at Johannes
Gutenberg University Mainz (JGU) have been able to see, for the first
time, the dramatic changes that occur in the DNA of cells that are
starved of oxygen and nutrients. This starved state is typical in some
of today’s most common diseases, particularly heart attack, stroke, and
cancer. The findings provide new insight into the damage these diseases
cause and may help researchers to discover new ways of treating them.
When a person has a heart attack or a stroke,
the blood supply to part of their heart or brain is blocked. This
deprives affected cells there of oxygen and nutrients, a condition known
as ischaemia, and can cause long-term damage, meaning that the person
may never fully recover. Ina Kirmes, a PhD student in the group of Dr.
George Reid at IMB, investigated what happens to the DNA in cells that
are cut off from their oxygen and nutrient supply.
In a healthy cell, large parts of the DNA are
open and accessible. This means that genes can be easily read and
translated into proteins, so that the cell can function normally.
However, the researchers showed that, in ischaemia, DNA changes
dramatically: it compacts into tight clusters. The genes in this clumped
DNA cannot be read as easily anymore by the cell, their activity is
substantially reduced, and the cell effectively shuts down. If cells in a
person’s heart stop working properly, this part of the heart stops
beating and they will have a heart attack. Similarly, when blood supply
is blocked to cells in someone’s brain and their cells there are starved
of oxygen and nutrients, they have a stroke.
Dr. George Reid is excited about the
implications of this finding. “When you have a stroke, when you have a
heart attack, this is likely to be what’s happening to your DNA,” he
explained. “Now we know that this is what’s going on, we can start to
look at ways of preventing this compaction of DNA.”
The key to this discovery was a close collaboration with Aleksander
Szczurek, joint first author on this publication, who is part of the
group of Professor Christoph Cremer at IMB. They developed a new method
that made it possible to see DNA inside the cell at a level of detail
never achieved before. Their technique is a further development of
super-resolution light microscopy, which uses blinking dyes that bind to
DNA to enable the researchers to define the location of individual
molecules in cells. This novel technology has been described in a
separate paper, published in Experimental Cell Research in September 2015.