Children born with rare, inherited conditions known as Congenital Disorders of Glycosylation, or CDG, have mutations in one of the many enzymes the body uses to decorate its proteins and cells with sugars. Properly diagnosing a child with CDG and pinpointing the exact sugar gene that’s mutated can be a huge relief for parents—they better understand what they’re dealing with and doctors can sometimes use that information to develop a therapeutic approach. Whole-exome sequencing, an abbreviated form of whole-genome sequencing, is increasingly used as a diagnostic for CDG.
The three children in this study, from left to right: Oliver, Edward, and Amira-Zoe.
Muscle from normal mice (left) and a mouse model lacking ERRgamma and ERRbeta (right) differ in muscle fiber-type, as indicated by immunofluorescence staining (green = myosin heavey chain 1, blue = myosin heavy chain 2a)
Sanford-Burnham researchers identify microRNAs as the missing link between the two defining features of muscle fitness—fuel-burning and fiber-type switching—providing a potential new target for interventions that boost fitness in people with chronic illness or injury.
Researchers discovered that small pieces of genetic material called microRNAs link the two defining characteristics of fit muscles: the ability to burn sugar and fat and the ability to switch between slow- and fast-twitch muscle fibers. The team used two complementary mouse models—the “marathon mouse” and the “couch potato mouse”—to make this discovery. But what’s more, they also found that active people have higher levels of one of these microRNAs than sedentary people. These findings, published May 8 in The Journal of Clinical Investigation, suggest microRNAs could be targeted for the development of new medical interventions aimed at improving muscle fitness in people with chronic illness or injury.
Quebec (Photo by Martin St-Amant, Wikimedia Commons)
Calling all cytokine scientists…
What: 14th International Tumor Necrosis Factor Conference
When: July 7-10, 2013
Where: Loews Le Concorde, Quebec City, Canada
Who: Hosted by the International Cytokine Society; attended by more than 300 academic and biopharma industry scientists from around the world
Registration: Visit www.tnf2013.com
Sanford-Burnham will co-host the 9th annual World Stem Cell Summit December 4-6, 2013, in San Diego, together with The Scripps Research Institute, Genetics Policy Institute, Mayo Clinic, and California Institute for Regenerative Medicine.
Sanford-Burnham will co-host the 9th annual World Stem Cell Summit December 4-6, 2013, in San Diego, together with The Scripps Research Institute (TSRI), Genetics Policy Institute (GPI), Mayo Clinic, Kyoto University Institute for Integrated Cell-Material Sciences (iCeMS), and California Institute for Regenerative Medicine (CIRM). The large, multi-disciplinary conference features more than 170 experts, who will discuss the latest scientific discoveries, business models, translational issues, legal and regulatory solutions, and best practices.
Today, April 8, 2013, at 11 a.m. ET, thousands of patient and research advocates, survivors, researchers, clinicians, business leaders, and members of the general public will gather on the steps of the Carnegie Library in Washington, D.C., to Rally for Medical Research. The event, organized by the American Association for Cancer Research, calls on our nation’s policymakers to prioritize medical research funding. This is a unified call for sustained investment in the National Institutes of Health (NIH), an investment to improve health, spur progress, inspire hope, and save lives.
How can you participate?
Giuseppina Claps received her JMNMF award at a special recognition ceremony. She is pictured here with her mentor Ze'ev Ronai (left) and Robert Rickert (right), associate dean of the Sanford-Burnham Graduate School of Biomedical Sciences.
Congratulations to Giuseppina Claps, a student in the Sanford-Burnham Graduate School of Biomedical Sciences, on receiving one of ten nationally competitive 2013 Research Scholar Awards from the Joanna M. Nicolay Melanoma Foundation (JMNMF)! These $10,000 grants support exceptional graduate student research in melanoma.
Malene Hansen, Ph.D., assistant professor in our Del E. Webb Center for Neuroscience, Aging, and Stem Cell Research and native of Denmark, gave a faculty promotion seminar last week. It was her chance to show off her science and service to a committee that will evaluate her for promotion to associate professor. Check out her lab members in attendance. They’re showing their support with Danish flag scarves! Best of luck to Hansen and her team.
Left: In fat tissue from a lean mouse, neutrophil elastase and a1-antitrypsin levels are balanced. Right: In fat tissue from an obese mouse, they are imbalanced—neutrophil elastase levels are high (dark staining) and a1-antitrypsin levels are low.
Imbalance between an enzyme called neutrophil elastase and its inhibitor causes inflammation, obesity, insulin resistance, and fatty liver in mice and humans—providing a new therapeutic target for these health conditions
Many recent studies have suggested that obesity is associated with chronic inflammation in fat tissues. In a new study, researchers discovered that an imbalance between an enzyme called neutrophil elastase and its inhibitor causes inflammation, obesity, insulin resistance, and fatty liver disease. This enzyme is produced by white blood cells called neutrophils, which play an important role in the body’s immune defense against bacteria.
Left to Right: Rep. Darrell Issa; Dr. Kristiina Vuori, Sanford-Burnham president and interim CEO; Greg Lucier, Life Technologies CEO (Photo by Augustine Agado, Life Technologies)
San Diego is a hub for life science research. According to San Diego Regional EDC, the region is home to more than 600 life science companies and 80 research institutes, which employ more than 42,000 people. Much of this industry is located in California’s 49th Congressional District, represented by Congressman Darrell Issa, chairman of the House Oversight and Government Reform Committee. Last Friday, Rep. Issa sat down with many of San Diego’s life science leaders.
Neurons from a normal mouse (left) are longer and fuller than neurons from a mouse lacking SNX27 (right).
Researchers discover that the extra chromosome inherited in Down syndrome impairs learning and memory because it leads to low levels of SNX27 protein in the brain.
What is it about the extra chromosome inherited in Down syndrome—chromosome 21—that alters brain and body development? Researchers have new evidence that points to a protein called sorting nexin 27, or SNX27. SNX27 production is inhibited by a molecule encoded on chromosome 21. The study, published March 24 in Nature Medicine, shows that SNX27 is reduced in human Down syndrome brains. The extra copy of chromosome 21 means a person with Down syndrome produces less SNX27 protein, which in turn disrupts brain function. What’s more, the researchers showed that restoring SNX27 in Down syndrome mice improves cognitive function and behavior.
Beaker by the numbers:
Sanford-Burnham’s Beaker blog is 3 years old today!
On March 24, 2010, we published the very first blog post
Since then, we’ve published 538 posts - an average of one post every 2 days
19 regular and guest bloggers have contributed to Beaker
329,059 people have visited the site
Skeletal myospheres ("mini muscles") generated by adding MyoD and BAF60C to embryonic stem cells
To make “mini muscles” from stem cells, you need the protein BAF60C.
Pier Lorenzo Puri, Ph.D., and his team study what makes a muscle cell just that—a muscle cell. They’re especially interested in applying that information to regenerate new muscle for people with muscular dystrophy.
Last year, the team discovered that two proteins called MyoD and BAF60C work together to mark the DNA of precursor cells, setting them on a course to become muscle cells. When the MyoD/BAF60c complex receives the right signals, it unwinds the cell’s genome and begins the process of producing muscle-specific proteins. This chain of events eventually triggers these precursor cells—those that hang out in our normal muscle tissue—to mature into new muscle cells.
Siah2 levels (brown staining) are high in human castration-resistant prostate cancer (left), as compared to benign prostate growths (right)
Researchers discover that a protein called Siah2 helps prostate cancer cells resist hormone therapy—making it an attractive biomarker and therapeutic target.
Hormonal therapies can help control advanced prostate cancer for a time. However, for most men, at some point their prostate cancer eventually stops responding to further hormonal treatment. This stage of the disease is called androgen-insensitive or castration-resistant prostate cancer. In a study published March 18 in Cancer Cell, a research team found a mechanism at play in androgen-insensitive cells that enables them to survive treatment. They discovered that a protein called Siah2 keeps a portion of androgen receptors constantly active in these prostate cancer cells. Androgen receptors—sensors that receive and respond to the hormone androgen—play a critical role in prostate cancer development and progression.
3D structure of HNF-4α, a protein mutated in MODY1, a rare, inherited form of diabetes, reveals new pockets that could be targeted with therapeutic drugs
Researchers have determined the complete three-dimensional structure of a protein called HNF-4α. HNF-4α controls gene expression in the liver and pancreas, switching genes on or off as needed. People with mature onset diabetes of the young (MODY1), a rare form of the disease, have inherited mutations in the HNF-4α protein. This first-ever look at HNF-4α’s full structure, published today in Nature, uncovers new information about how it functions. The study also reveals new pockets in the protein that could be targeted with therapeutic drugs aimed at alleviating MODY1.
Michael Jackson, Ph.D., vice president of drug discovery and development in Sanford-Burnham's Conrad Prebys Center for Chemical Genomics (photo by Mark Dastrup)
We announced today that we’ve signed a new collaborative agreement with Mayo Clinic to build a pipeline of therapeutic drugs aimed at a variety of diseases with serious unmet medical needs. Under this agreement, Mayo Clinic scientists will work with researchers in our Conrad Prebys Center for Chemical Genomics (Prebys Center) to conduct early-stage drug discovery, including assay development, high-throughput screening, and lead identification.