Life in a bubble: Nobel secrets of body's cell transport system

A portrait of US scientist Randy W Schekman and drafts of his work are displayed on a screen during a press conference to announce the winners of the 2013 Nobel Prize in medicine on October 7, 2013 in Stockholm

08 oct 2013--Vesicles, the bubble-shaped vessels that transport molecules within cells, may hold the secret to halting viruses or even combating Alzheimer's, say experts who hailed Monday's Nobel awarded to three leaders in the field.

Thousands of these sac-like cargo vehicles reside in every human cell.

Their job is to transport molecules within and between cells.

Vesicles are crucial for the very functioning of cells—shipping everything from neurotransmitter molecules responsible for signalling in the brain to hormones and immune responses to viral intruders.

When things go well, the vesicles are like trucks providing just-in-time delivery of parts for a factory buzzing with activity.

But if vesicles arrive too late or too early, or go to the wrong place, they can cause the cell to malfunction—a potential trigger for disease. They also allow viruses to propagate by transporting viral proteins within cells.

"Very fundamental processes in life depend on vesicular transport," Dick Hoekstra, cell biology professor at the University of Groningen in the Netherlands, told AFP.

"All organelles (compartments) within a cell are communicating with each other via vesicles," he said. "The way that viruses reproduce is also very much dependent on the vesicular transport system."

Inside cells is a hive of machinery that cranks out proteins, the molecules that sustain the cell and enable it to function, but also help it work with other cells.

Most molecules produced by cells are too large to pass through cell membranes and thus are transported instead by vesicles.

The vesicles are coated with fatty membranes that "fuse" with the membranes on other vesicles, to pass on their cargo, a bit like water drops merging on a window pane.

They are able to identify their destination thanks to an "address code" of proteins studding the membrane. The proteins are like the matching sides of a zip: when they fit, two vesicles merge and the cargo is transferred.

"Its almost like a bubble hitting a wall and the contents of that bubble are then released," explained Mike Cousins, chairman of neuronal cell biology at Edinburgh University.

Each vesicle is about 50 nanometres (billionths of a metre) in diameter and transfers about a million molecules at a time.

Vesicles continually "bud off" from one cell membrane, bulging out to fuse to another, then releasing their precious, molecular cargo.

The three men honoured by the Nobel Assembly on Monday, US duo James Rothman and Randy Schekman and German-born Thomas Suedhof, have put decades of work into shedding more light on how vesicles work—and why, sometimes, they do not.

Schekman figured out which genes were responsible for mixing up the transport system, which can cause vesicles to pile up in parts of the cell like a traffic jam.

Rothman discovered that a protein complex enables vesicles to dock and fuse.

Suedhof took the work further by showing more precisely how the protein "zipper" opens up to allow neurotransmitters to move between nerve cells in the brain.

The knowledge has helped us understand the important role that vesicles may be playing in diseases like diabetes and immune disorders.

"In the last five years it is looking like presynaptic disfunction, messed-up vesicle transport, is underlying a lot of potential neurodevelopmental disorders like... autism," said Cousins.

"There is also accumulating evidence that it is going to be very important in neurodegenerative diseases: Alzheimer's disease, Parkinson's disease."

Hoekstra said better understanding of vesicles may also benefit other medical fields: his department is researching vesicle-like ways of bypassing the so-called blood-brain barrier, a circulatory cut-off between blood flow to the brain and the rest of the body, to make it easier for doctors to administer drugs to the organ.

AIDS pioneers and cancer scientist win Nobel prize

By Niklas Pollard
07 oct 2008--Two French scientists who discovered the AIDS virus and a German who bucked conventional wisdom to find a virus that causes cervical cancer were awarded the 2008 Nobel prize for medicine on Monday.
Luc Montagnier, director of the World Foundation for AIDS Research and Prevention, and Francoise Barre-Sinoussi of the Institut Pasteur won half the prize of 10 million Swedish crowns ($1.4 million) for discovering the virus that has killed 25 million people since it was identified in the 1980s.
Dr. Harald zur Hausen of the University of Duesseldorf and a former director of the German Cancer Research Center shared the other half of the prize for work that went against the established opinion about the cause of cervical cancer.
"The three laureates have discovered two new viruses of great importance and the result of that has led to an improved global health," said Jan Andersson, a member of the Nobel Assembly at Sweden's Karolinska Institute.
The discoveries made it possible to diagnose both infections, and led to the development of two vaccines that prevent cervical cancer, and more than 20 drugs that can keep HIV patients healthy.
But Montagnier said those who most need the diagnosis and treatments for AIDS are not getting either.
"It's Africa which is carrying the weight of the epidemic at this moment. Out of millions of people infected, a large number are not being treated, either because they don't have access to treatment or because they don't know they are infected," Montagnier told Reuters in Abidjan, Ivory Coast, where he was giving a lecture.
The award is a decisive vote for Montagnier in a long-running dispute over who discovered and identified the virus, Montagnier or Dr. Robert Gallo, then of the U.S. National Cancer Institute.
"There was no doubt as to who made the fundamental discoveries," Nobel Assembly member Maria Masucci told Reuters.
CANCER DISCOVERY
Zur Hausen was recognized for finding that the human papilloma virus, or HPV, caused cervical cancer.
"More than 5 percent of all cancers worldwide are caused by persistent infection with this virus," the Nobel committee said. The virus, which infects at least half of all sexually active adults, can also cause genital warts, cancer of the penis and other genitalia.
The German scientist, who began his research in the 1970s, searched for different HPV types, detecting them in 70 percent of cervical tumor samples from around the world.
An estimated 500,000 women are diagnosed with the disease each year and about 300,000 die from it, mostly in the developing world.
Zur Hausen said he thought more cancers would be linked to viruses. "I suspect there will be more in the future," he said in a telephone interview.
GlaxoSmithKline and Merck and Co. have developed vaccines against HPV -- which are controversial because to be effective the series of costly shots must be given to girls before they begin sexual activity.
Medicine is traditionally the first of the Nobel prizes awarded each year. The prizes for achievement in science, literature and peace were first awarded in 1901 in accordance with the will of dynamite inventor Alfred Nobel.
The Nobel laureate for physics will be announced on Tuesday, chemistry on Wednesday, literature on Thursday and the Nobel Peace Prize on Friday in Oslo.

Medicine award kicks off Nobel Prize announcements

By KARL RITTER
06 oct 2008--Two scientists who have won acclaim for research into the growth of cancer cells could be candidates for the Nobel Prize in medicine when the 2008 winners are presented on Monday, kicking off six days of Nobel announcements.
Australian-born U.S. citizen Elizabeth Blackburn and American Carol Greider have already won a series of medical honors for their enzyme research and experts say they could be among the front-runners for a Nobel.
Only seven women have won the medicine prize since the first Nobel Prizes were handed out in 1901. The last female winner was U.S. researcher Linda Buck in 2004, who shared the prize with Richard Axel.
Among the pair's possible rivals are Frenchman Pierre Chambon and Americans Ronald Evans and Elwood Jensen, who opened up the field of studying proteins called nuclear hormone receptors.
As usual, the tightlipped award committee is giving no hints about who is in the running before presenting its decision in a news conference at Stockholm's Karolinska institute.
Alfred Nobel, the Swede who invented dynamite, established the prizes in his will in the categories of medicine, physics, chemistry, literature and peace. The economics prize is technically not a Nobel but a 1968 creation of Sweden's central bank.
Nobel left few instructions on how to select winners, but medicine winners are typically awarded for a specific breakthrough rather than a body of research.
Hans Jornvall, secretary of the medicine prize committee, said the 10 million kronor (US$1.3 million) prize encourages groundbreaking research but he did not think winning it was the primary goal for scientists.
"Individual researchers probably don't look at themselves as potential Nobel Prize winners when they're at work," Jornvall told The Associated Press. "They get their kicks from their research and their interest in how life functions."
Blackburn, of the University of California, San Francisco, and Greider, of Johns Hopkins University in Baltimore, won Germany's Paul Ehrlich Ludwig Darmstaedter Prize earlier this year for studying how the enzyme telomerase affects cells.
In 2006, they shared the Lasker prize for basic medical research, often dubbed "America's Nobel," with Jack Szostak of Harvard Medical School. The trio's work set the stage for research suggesting that cancer cells use telomerase to sustain their uncontrolled growth.
Many Lasker winners go on to win Nobel Prizes, including last year's Nobel laureates Mario Capecchi and Oliver Smithies of the United States and Briton Martin Evans, who won the Lasker prize in 2001.
Science writer Karin Bojs of Swedish newspaper Dagens Nyheter, a leading Nobel guesser, predicted a shared medicine prize between Italy's Giacomo Rizzolatti and Finland's Riitta Hari for research on so-called "mirror neurons" in monkeys and humans.
In its annual predictions, the scientific division of Thomson Reuters put forth Japanese researcher Shizuoa Akira, American Bruce Beutler and Jules Hoffman of France "for their research on toll-like receptors and innate immunity."
The prizes are handed out every year on Dec. 10, the anniversary of Nobel's death in 1896.