Since the sequencing of the human genome in 2001, all our genes – more than
20,000 in total – have been identified. But much information, such as where and
when each is active, is still unknown. Next to each gene sits a short DNA
segment, and the activity of this regulatory segment determines whether the gene
will be turned on, where and how strongly. These short regulatory segments are
just as – if not more – important than the genes themselves.
percent of the mutations that cause disease occur in these regulatory areas.
They are responsible for the proper development of tissues and organs,
determining – for example – that eye cells, and only eye cells, contain light
receptors, while only pancreatic cells produce insulin. Clearly, a deeper
understanding of this regulatory system, its mechanisms and possibilities for
malfunction may lead to advances in biomedical research, especially in
developing targeted therapies for individual patients.
In spite of their
importance, the “regulatory code” is not well understood. To address this
problem, a research team led by Dr. Ido Amit of the Weizmann Institute of
Science’s immunology department together with scientists Manuel Garber, Nir
Yosef and Aviv Regev from the Broad Institute in Massachusetts, and Nir Friedman
of the Hebrew University of Jerusalem, developed an advanced automated system
for mapping these sites, and then used this system to uncover important
principles regarding how these regulatory elements function.
things, their study, which recently appeared in Molecular Cell, revealed a
hierarchical structure for the regulatory code. By mapping a large number of
regulatory factors, the team revealed an overall plan for gene regulation as
well as the intimate details of the mechanisms involved in the immune response.
The process used for the past 30 years to map regulatory elements has been
complicated, complex and labor-intensive, requiring huge scientific consortiums
to accomplish the task. With the new method, just a handful of researchers were
able to conduct a study on a similar scale to the mega-team ones, and in a
fraction of the time.
Their highly efficient, automated method enabled
Amit and his team to measure a large number of regulatory proteins and their
binding sites in parallel. They exposed immune cells to bacteria – setting the
stage for gene activation – and then traced the actions of several dozen
different regulatory proteins known to play a role in the immune response over
four points in time.
Not only were the researchers able to identify the
binding locations of each and the genes they activate, but the levels of
activation and the mechanisms employed.
One of their more significant
findings was that the actions of these regulatory factors can be neatly
classified into three levels in a sort of regulatory hierarchy. In the bottom
tier are those factors that create the rough divisions into main cell types by
directing cell differentiation. These factors are the “basic identity” guides
that can, on their own, determine whether a cell will have the characteristics
of a muscle cell or a nerve cell, for example. On the second tier are the
regulatory factors that determine a cell’s sub-identity, which they do by
controlling the strength of a gene’s expression. These factors are in charge of
producing closely-related sub-types, for instance, muscle fibers that are either
smooth or striated, or closely- related immune cells. Regulatory factors in the
third tier are even more specialized, affecting the expression of certain genes
in response to signals from outside the cell, such as bacterial invaders,
hormones and hunger pangs.
They hope that understanding the ins and outs
of the regulatory code will help researchers to understand and predict how
diseases arise and progress due to malfunctions in regulatory
In the future, understanding the regulatory program may lead
to advances in rehabilitative medicine. Regulatory mechanisms could be used to
redirect the differentiation of a patient’s cells, which could then be
re-implanted, thus avoiding the problems inherent in using donor
“The new method for mapping the gene’s regulatory plan may open
new vistas for investigating all sorts of biological processes, including the
system failures that occur in disease,” Amit concludes.
CLEANING UP WITH
To the afficionado of sweets, it would seem to be a waste, but
researchers at the University of Southern Mississippi have developed a new
oil-spill dispersant made from ingredients found in ice cream, chocolate and
peanut butter. The discovery was reported at a recent meeting of the American
With concerns about the possible health and
environmental effects of oil dispersants in the various gasoline spills around
the world, new dispersants are needed that can be made from edible ingredients
and can both break up oil slicks and keep oil from sticking to the feathers of
“Each of the ingredients in our dispersant is used in common food
products like peanut butter, chocolate and whipped cream,” said Dr. Lisa K.
Kemp. “Other scientists are working on new oil dispersants and absorbents, but
nothing that’s quite like ours. It not only breaks up oil but prevents the
deposition of oil on birds and other objects, like the ingredients in laundry
detergent keep grease from redepositing on clothing in the rinse cycle. Birds
can sit in slicks of the dispersed oil, they can dive through it and take off
and flap their wings, and the oil will fall off.”
The new dispersant is
based on scientific principles established decades ago during the development of
modern laundry detergents. One ingredient, for instance, is a special polymer
that sticks to the surface of oil droplets to keep them from sticking to the
feathers of sea birds. Similar polymers in laundry detergents keep oil and
grease removed during the wash cycle from getting back on clothing during the
When detergents are used to remove oil that has coated fur
or feathers, it defeats their natural waterproofing effect, leaving birds less
buoyant and more susceptible to hypothermia. Birds can also ingest the oil as
they try to clean themselves, causing internal damage.
advantage, Kemp noted, is the ease of quickly obtaining large amounts of
ingredients for making the dispersant at reasonable cost. She envisioned
agencies like the US Coast Guard keeping small amounts on hand for first
response, with larger quantities being quickly made as necessary.