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This aims to bring cutting edge technology across the Councils’ portfolios into vaccine development and early-stage manufacturing research, and foster research that may be applicable across different diseases. EOIs will not be assessed on their scientific quality but the Research Councils will decide internally whether the expression of interest fits the aims of this joint highlight notice and with which Council your proposal sits best. Vaccinology proposals will be in competition with all other proposals that come into response-mode competitions; however the Councils will use the EOI to manage funding demand and may at their discretion re-profile budget accordingly.
Applications will be processed by one council, but we will consider collaborative funding where appropriate. Applicants are advised to contact the Councils on the above contact if they are thinking of submitting an application under this highlight. One day in 1788, students at the Hunterian School of Medicine in London were opening a cadaver when they discovered something startling. The students had never seen anything like it, and they rushed to find their teacher, the Scottish physician Matthew Baillie, who was just as stunned as they were. His report was the first detailed description of the condition, which came to be known as situs inversus and is thought to occur in about 1 in 20,000 people.
Mutations that cause situs inversus can lead to a number of serious disorders, including congenital heart defects. But these visible changes arise long after the embryo has developed differences on its left and right. Biologists have pinpointed a single spot where this symmetry breaking starts: a tiny pit called the node, on the embryo’s midline. The tilt of the cilia is so important because the embryo is bathed in a thin film of fluid; if they were upright, they would push the fluid in all directions, creating no flow at all.
It takes only a very weak flow to the left side to start an embryo on its proper development: Last year, scientists at Osaka University in Japan reported that the whirling of just two cilia were enough to get the job done. And that raises another question: “What on earth are we doing with all those cilia if we don’t need them?” as Dr. Once the fluid starts flowing, it takes only three or four hours for the left and right sides to be determined.


In the first step, the fluid flows across the node until it reaches the left side of the rim. Regardless of those details, the cilia on the rim of the node respond to the flow — possibly by releasing calcium atoms that then spread to surrounding cells.
Scientists are still working out how Nodal helps determine the anatomy on each side of the body.
As she and her colleagues reported in the January issue of PLoS Genetics, the fast-moving cells on the left side drag the entire heart clockwise. As they look at these biological signals, scientists are also studying disorders that may be tied to their disruption. Situs inversus, the complete flip of the organs that Baillie described in 1788, may be the most dramatic of these disorders, but it is also one of the most harmless. The real danger, it appears, is in incomplete reversals — “when you get a confusion, when you get things not quite meeting,” as Dr.
In other cases, the heart grows correctly on the left side of the body, but the structures inside the heart — the valves and chambers — grow on the wrong side.
Propiedad intelectual: los derechos corresponden al autor del articulo o al medio de comunicacion en el que fue publicado. BBSRC, EPSRC and MRC will agree the percentage commitment to each application at the full application stage.
Baillie argued that if doctors could figure out how this strange condition came to be, they might come to understand how our bodies normally tell the right side from the left.
Deciphering the effects of mutated genes could lead to diagnoses and treatments for those conditions. Experiments have revealed that the early embryo produces different proteins on each side while it still looks symmetrical. The interior of the node is lined with hundreds of tiny hairs, called cilia, which whirl round and round at a rate of 10 times a second. Those cells respond by spewing out a protein called Nodal, which spreads through the left side of the embryo, in turn spurring other cells to spew out Nodal of their own in a kind of feedback loop that leaves the left side loaded with Nodal and the right with almost none.


In recent years, many researchers have focused not on mice but on zebra fish, which have the advantage of having transparent embryos; cells in the embryos can be engineered to glow so the organs can be observed taking shape.
Burdine, at Princeton, studies how Nodal shapes the anatomy of the zebra fish heart as embryonic cells migrate around the organ. Scientists have long known that the two sides of the human brain have some important differences. These disorders may not be immediately fatal, but they can become dangerous later in life, requiring complex surgery to rearrange the heart.
Burdine hopes that research on left-right disorders will lead to genetic tests that can predict the risk of these hidden heart defects. They have pinpointed some of the steps by which embryos’ organs develop on the left or right. The heart then starts to grow different structures on each side, producing the chambers and vessels required to pump blood.
The right hemisphere, for example, plays a big role in understanding the mental lives of other people; the left hemisphere is important for focusing attention. Anderson and her colleagues at Memorial Sloan-Kettering Cancer Center disabled genes required to tip the cilia in the node. Other vertebrates also have left-right brain differences, but the origins of the imbalance are mostly a mystery.
Gamse and other researchers have found that Nodal prompts a small part of the fish’s brain to grow differently on the left and right sides. As they report in the journal Development, that mutation led to some mouse embryos’ developing a mirror-image anatomy.



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