Dual Role for Immune Cells in the Brain
We all have at one time or another experienced the typical signs of an infection: the fever, the listlessness, the lack of appetite. They are orchestrated by the brain in response to circulating cytokines, the signaling molecules of the immune system. But just how cytokines' reach extends beyond the almost impenetrable blood-brain barrier has been the topic of much dispute.
In their latest study, researchers at the Salk Institute for Biological Studies describe how, depending on the nature of the stimulus, resident macrophages lined up along the blood-brain barrier play opposing roles in the transmission of immune signals into the brain.
"These macrophages act as accelerators to enlist the brain's participation in dealing with immune insults, but when necessary slam on the brakes to prevent the central inflammatory response from going overboard," explains postdoctoral researcher Jordi Serrats, Ph.D., who co-led the study with Jennifer C. Schiltz, Ph.D., formerly a postdoctoral researcher in the Salk's Neuronal Structure and Function Laboratory and now an assistant professor at the Uniformed Services University in Bethesda, Maryland.
The Salk researchers' findings may pave the way for novel therapies for sufferers of chronic neurodegenerative diseases, such as Amyotrophic Lateral Sclerosis (ALS), Parkinson's, Alzheimer's and prion diseases, in which central inflammatory mechanisms play an important role.
Grant Writing Webinar for Companies
The California Institute for Regenerative Medicine plans to offer a webinar to help life science companies interested in stem cell research learn how to apply for state-funded stem cell grants.
The webinar is scheduled for March 3, from 1 p.m. to 4p.m. Instruction will be given on how to understand the stem cell agency's RFA and grant process. Participants will also receive guidance on writing a successful grant. More information will be available on CIRM's website, as the date approaches.
VWR Makes a Difference for Children
VWR International and the VWR Foundation jointly raised $40,000 for Children’s Medical Center of Dallas earlier this month through an auction. The auction took place during VWR's three-day North American sales meeting in Dallas. More than 90 items were put on the auction block to raise the money that will be specifically directed to the Center for Cancer and Blood Disorders. A check was presented to the hospital on Jan. 19.
The VWR Foundation was started by five associates of VWR International, who wanted to make a difference in the areas in which they worked and lived. The foundation was officially established in January 2009 and focuses on research, health and well-being and science education. For more information about the VWR Foundation, visit www.VWRfoundation.org.
VWR International, is headquartered in West Chester, Pennsylvania. It is a global laboratory supply and distribution company with worldwide sales in excess of $3.7 billion. VWR enables the advancement of the world’s most critical research through the distribution of a highly diversified product line to most of the world’s top pharmaceutical and biotech companies, as well as industrial, educational, and governmental organizations.
Researchers Find New Insights into Inherited Retinal Disease
An international team of scientists, led by researchers at the University of California, San Diego School of Medicine have discovered new links between a common form of inherited blindness affecting children and a gene known as Abelson helper integration site-1 (AHI1). Their findings, which may lead to new therapies and improved diagnostics for retinal disease, will appear online in advance of publication in the journal Nature Genetics on January 17.
A newly recognized class of disease known as “ciliopathies” has caught the attention of the medical community. Ciliopathies are caused by problems in the structure and/or function of cilia, which are small antenna-like structures protruding from the surface of most cells.
The function of cilia has not been understood, but patients with ciliopathies can suffer from a spectrum of problems including retinal blindness, obesity, renal failure, liver fibrosis and mental impairment. Major breakthroughs in the past few years have linked many forms of these diseases with defects in the structure or signaling capacity of the cilia in cells as diverse as retinal, fat, kidney, liver and nerve cells. Because cilia are so widely present on cells throughout the body, many seemingly unrelated diseases are now known to be related through functions of cilia.
UC San Diego Researchers Synchronize Blinking “Genetic Clocks”
Researchers at UC San Diego who last year genetically engineered bacteria to keep track of time by turning on and off fluorescent proteins within their cells have taken another step toward the construction of a programmable genetic sensor. The scientists recently synchronized these bacterial “genetic clocks” to blink in unison and engineered the bacterial genes to alter their blinking rates when environmental conditions change.
Their latest achievement is a crucial step in creating genetic sensors that might one day provide humans with advance information about temperature, poisons and other potential hazards in the environment by monitoring changes in the bacterium’s blinking rates. A video showing the UCSD team’s blinking genetic clocks can be seen here.
Scientists Show How Brain Tumors Outsmart Drugs
Researchers at the Ludwig Institute for Cancer Research (LICR) at the University of California, San Diego School of Medicine and Moores UCSD Cancer Center have shown one way in which gliomas, a deadly type of brain tumor, can evade drugs aimed at blocking a key cell signaling protein, epidermal growth factor receptor (EGFR)that is crucial for tumor growth. In a related finding, they also proved that a particular EGFR mutation is important not only to initiate the tumor, but for its continued growth or “maintenance” as well.
The findings provide both new insights into the behavior of gliomas as well as potential new drug targets and treatment strategies.
Scripps Team Finds Stress Hormone Key to Alcohol Dependence
A team of scientists from The Scripps Research Institute has found that a specific stress hormone, the corticotropin-releasing factor (CRF), is key to the development and maintenance of alcohol dependence in animal models. Chemically blocking the stress factor also blocked the signs and symptoms of addiction, suggesting a potentially promising area for future drug development.
The new study, a culmination of more than six years of research, not only confirms the central role of CRF in alcohol addiction using a variety of different methods, but also shows that in rats the hormone can be blocked on a long-term basis to alleviate the symptoms of alcohol dependence.
Previous research had implicated CRF in alcohol dependence, but had shown the effectiveness of blocking CRF only in acute single doses of an antagonist (a substance that interferes the physiological action of another). The current study used three different types of CRF antagonists, all of which showed an anti-alcohol effect via the CRF system. In addition, the chronic administration of the antagonist for 23 days blocked the increased drinking associated with alcohol dependence.
Tobacco Smoke Causes Lung Inflammation, Promotes Lung Cancer Growth
Repeated exposure to tobacco smoke makes lung cancer much worse, and one reason is that it steps up inflammation in the lung. Scientists at the University of California, San Diego School of Medicine have found that mice with early lung cancer lesions that were repeatedly exposed to tobacco smoke developed larger tumors – and developed tumors more quickly – than unexposed animals. The key contributing factor was lung tissue inflammation.
The results of their study provide definitive evidence for the role of lung inflammation brought on by chronic exposure to tobacco smoke in promoting lung cancer growth. The findings also establish new lung cancer models, provide insights into both the development and growth of lung cancer, and suggest the possibility of using anti-inflammatory agents to prevent or slow lung cancer progression, said Michael Karin, PhD, Distinguished Professor of Pharmacology and Pathology at the UC San Diego School of Medicine, who led the work.
“We’ve shown for the first time that tobacco smoke is a tumor promoter – not only a tumor initiator – and that it works through inflammation,” said Karin, director of the Laboratory of Gene Regulation and Signal Transduction and a member of the Moores UCSD Cancer Center. “Other particulate materials, such as fine silicon dust, asbestos and coal dust, may promote lung cancer development through similar mechanisms. Such substances were never found to induce mutations, which are the essence of tumor formation. More research is needed to explore the role and biochemical mechanisms of exposure to pro-inflammatory substances in the environment in early stages of cancer development.”
SDSC Joins Other UC San Diego Departments, LLNL in Oncology Collaboration
Researchers from the San Diego Supercomputer Center (SDSC) at UC San Diego have joined forces with the Department of Radiation Oncology in the university’s School of Medicine, its Department of Mathematics, and the Lawrence Livermore National Laboratory (LLNL) in a three-year, $1.5 million project to pursue novel applications of high-performance computing (HPC) in radiotherapy.
Under the project, called SCORE for SuperComputing Online Re-planning
Environment,
SDSC researchers are collaborating with oncology researchers to
redesign treatment plans leveraging HPC resources and expertise. The project was
awarded from a University of California Office of the President grant based on
the Lab Fees Research Program in 2009.
The ultimate goal of the proposed HPC-based radiation therapy, specifically referred to as ‘Adaptive Radiation Therapy (ART) Based on High-Performance Computing,’ is to deliver a prescribed radiation dose to targets containing tumors and cancerous regions, while sparing surrounding functional organs and normal tissues.
Keep an Eye on These Local Researchers
Sheng Ding, associate professor of chemistry at The Scripps Research Institute
(TSRI) was responsible for one of the biggest scientific discoveries reported in
2009: a method to convert adult cells all the way back to the most primitive
embryonic like cells without using the dangerous genetic manipulations
associated with previous methods.
Keep an eye on Ding and his TSRI lab as
well as the San Diego-based company he founded (Fate Therapeutics), which uses
the technology platform.
Time magazine has ranked the mapping of the
first human epigenome, led by Salk Institute researcher Joseph Ecker, as the No.
2 scientific discovery of 2009. Using the new high-resolution maps as a research
tool, Ecker's group will now examine how the epigenome changes during normal
development as well as examining a variety of disease states.
Michael B. A. Old-stone, professor and head of the Viral-Immunobiology Laboratory at The Scripps Research Institute is a leader in his field. He is also the author of the critically acclaimed book Viruses, Plagues, and History: Past, Present and Future. Readable books about viruses by experts are few and far between. Originally published in 1998, last year the book was reissued as a revised and expanded edition. Now that's staying power. Oldstone will discuss his book at 7 p.m. Jan. 30, at D.G.Wills Books, 7461 Girard Ave., La Jolla.
Article published in La Jolla Light.
TSRI Finds Link Between Fat Cells, Cancer's Aggressiveness
An enzyme that normally helps break down stored fats goes into overdrive in
some cancer cells, making them more malignant, according to new findings by a
team at The
Scripps Research Institute. The aggressiveness-promoting enzyme, called
monoacylglycerol lipase (or MAGL for short), may provide a new target for
treating more malignant forms cancers or for preventing cancer progression. The
findings also suggest an explanation for the reported link between obesity and
cancer by showing that releasing stored fats in cancer cells can push them
toward more aggressive behaviors.
As a cancer grows inside the body, some
cells take on more aggressive characteristics, such as the ability to invade
local areas and to spread to other parts of the body. To identify possible
drivers in this process, postdoc Daniel Nomura compared changes in the
functional state of enzymes in non-aggressive cancer cells to that of aggressive
ones by using a technique called activity-based protein profiling, which allows
researchers to survey all active enzymes in a cell at once.
Among the many enzymes detected, MAGL—a type of enzyme, called a lipase, that breaks down stored fats, or lipids—stood out as being highly elevated in aggressive cancers. Through a series of experiments where Nomura either inhibited or stimulated MAGL's activity, they were able to establish that this enzyme is capable of converting cancer cells from less to more malignant forms.
Scripps Team Wins Race To Achieve Landmark Synthesis Of Natural Product
In 1993 researchers discovered a chemical compound in a sponge off Palau, an island nation in the Pacific Ocean that has shown anticancer, antibacterial, and antifungal pharmaceutical promise. But that wasn't its greatest allure, at least not for chemists.
This compound, called Palau'amine, is so chemically complex and fragile that finding a way to produce it in the laboratory became the most hotly pursued synthetic chemistry goal in modern history. Groups around the globe dedicated millions to the challenge, but it is a team of scientists from The Scripps Research Institute that has finally completed the quest.
To Scripps Research chemist Phil Baran, Ph.D., who led the team that made the breakthrough, the project has already led to substantial benefits regardless of whether the compound or some derivative of it ever shows commercial success. Pharmaceutical companies are already using the silver oxidation technique to produce other potential drugs, students have received an invaluable, and other lessons learned about synthesizing challenging compounds will ultimately be applied in numerous other quests.
SDSU Office of International Programs Invites You to an Arctic Mystery
In 1897, three Swedes set out to explore the Arctic by balloon and are lost in
the ice…
Thirty-three years later, their remains are discovered, including
photos of the ill-fated journey. What went wrong? Did the three men ever have a
chance? What is the difference between comic fools and tragic heroes? The fate
of Salomon August Andrée and his two companions continues to intrigue Swedes and
the world to this day.
And on Sunday January 31, 2010, at 2.30 p.m., in
the Ulla “Lotta” Wiik Auditorium (AL 201) at SDSU, this question is explored in
Jan Troell’s award-winning film Flight of the Eagle with Max von Sydow,
followed by an excerpt from the play Fade to White by A.C.Harvey,
featuring San Diego actors David Heath, Tom Hall, and Michael Harvey. Robert
Swanson will enlighten you about ballooning, and the playwright will be
recognized.
This event is free and followed by a festive reception.
Visit http://www.swedishcenter.org for parking
information. Please note that the parking provided is free of charge.