Combining Chemists to Fight Lupus
Sometimes, the spark of two minds working together
can reveal surprising new ideas or discoveries. Such was the case
for an unusual partnership between chemists working in very different
areas who designed a potential new drug to treat lupus, a chronic
inflammatory disease caused when a person's immune system attacks
his or her own tissues. The potentially fatal disease is incurable,
and medicines used to treat its symptoms often have severe side
effects.
Gary Glick of the University of Michigan, Ann
Arbor, and his group were studying antibody molecules that attack
DNA, causing kidney damage similar to that seen in people with lupus.
The research team of Jonathan Ellman of the University of California,
Berkeley, was synthesizing a vast collection of different chemicals
and designing a fast, effective way to pick out the ones
with a desired activity.
By rapidly screening through their library of
compounds created through an approach called combinational
chemistry the researchers found a molecule that prevents
the disease in lupus-prone mice. The chemists are especially excited
about the molecule because it appears to lack the serious side effects
of current drugs. If the compound works as well in people, it may
be the basis for a long-sought new medicine to treat lupus.
Sugar-coated Cells and Inflammation
To study cell adhesion, Kiessling creates
long, sticky carbohydrate molecules (orange and gray) that interact
with receptors.
Photo: Laura Kiessling |
Most of our cells are studded with sticky,
sugary molecules. These molecules allow cells to adhere to each other,
which is key to activities that range from fertilization to infection.
And they have captured the attention of chemist Laura Kiessling of
the University of Wisconsin, Madison.
Kiessling focuses on sugar-coated molecules, called
L-selectins, that guide immune cells to the site of an injury. The
cells help fight infections, but when overzealous, they can cause
inflammation.
Kiessling's group is able to control the behavior
of L-selectin proteins and entire immune cells by
baiting them with custom-made, super-sugary molecules. By acting
as decoys that distract some of the immune cells, these molecules
may minimize inflammation and may be the basis of new anti-inflammatory
drugs.
Investigating Anesthesia and Alcohol
From
the early days of ether and strong whiskey, anesthetics have been
used for more than 100 years. But until recently scientists had
only a fuzzy notion of how they work.
Traditionally, scientists thought anesthetics
had no particular molecular target and deadened nerves merely by
seeping into cells. A team of researchers led by Neil Harrison,
now at the Weill Medical College of Cornell University, dislodged
this notion. The group pinpointed the part of a specific molecule
on the surface of nerve cells that is responsible for the action
of two common inhaled anesthetics. Interestingly, the same molecular
site also governs the intoxicating effects of alcohol.
This research may help scientists develop safer
and more effective anesthetics. For instance, it may allow them
to reverse the effect of these medications rapidly so that doctors
can awaken patients immediately after surgery. It may also shed
light on the molecular site responsible for alcohol's unpleasant
effects and perhaps on a new way to help treat alcoholics.
Saved by a Skin
Beauty, as they say, is more than skin deep. But
for severe burn victims, that thin layer of skin stretches precariously
between recovery and disability or death.
Our skin is not merely a convenient packaging
to cover up our insides. It also protects our bodies from dangerous
bacteria and viruses, regulates our internal temperature, and seals
in our vital fluids. Patients with severe burns face their greatest
risk from infection and from rapid, life-threatening fluid loss,
which jolts the body into shock and massive organ failure.
NIGMS-funded scientists developed, and continue
to improve upon, a type of artificial skin called Integra® Dermal
Regeneration Template, which is now the top-selling skin substitute
in the world. Integra®, which looks somewhat like clear cellophane
wrap, works as a temporary, protective covering that promotes healing.
After removing the damaged skin, surgeons drape Integra® or
a similar material over the wound and then apply a skin graft to
encourage new skin growth.
Within 2 to 4 weeks, the patient's own skin cells
grow into the scaffold provided by Integra®. Because patients
with serious burns covering most of their bodies may not have enough
healthy skin left to use for skin grafts, researchers are developing
a way to grow sheets of tissue suitable for grafts from just a few
of the patient's skin cells.
Thanks in large part to Integra® and to decades
of basic, NIGMS-supported research on burns and wound healing, the
grim prognosis faced by burn patients has brightened significantly.
Twenty years ago, patients with severe burns over half their bodies
rarely survived. Today, those patients usually recover and
so, incredibly, do some patients with severe burns over 90 percent
of their bodies.
|