Genomics: "Master switches" for muscular dystrophy?
Informatics: A weekend project grows up
In the 1980s, Louis Kunkel, PhD, director of Children's Hospital Boston's Program in Genomics, led the way in understanding the basis for muscular disorders by identifying the gene that causes Duchenne/Becker muscular dystrophy. Yet while scientists continue to link specific genes to muscular dystrophy and related disorders of muscle weakness and wasting, their understanding of these disorders is far from complete. It's largely unknown how the genes cause disease, and more importantly, how to translate the discoveries into treatments.
For instance, while scientists know that muscular dystrophy begins with mutations that cause small sections of muscle to die, they don't know what additional genes are involved in the subsequent, debilitating muscle loss.
Now, Kunkel and Iris Eisenberg, PhD, post-doctoral fellow in Genomics, offer the first study of microRNAs—tiny snippets of code that influence gene activity—in muscular disorders. Going after microRNAs, which have only recently been discovered, may uncover new genes and pathways involved in these devastating disorders and supply promising targets for stopping muscle loss.
As reported online in the Proceedings of the National Academy of Sciences on October 17, the researchers studied muscle samples from 88 people with 10 different types of muscle loss. Using gene chips, they compared microRNAs in wasting versus healthy human muscle, and found that 185 microRNAs are either too abundant or too scarce in wasting muscle. They then made lists of genes and pathways the microRNAs may control. Since microRNAs can regulate many genes at once, Eisenberg believes they may help orchestrate the tissue death, inflammatory response and other major degenerative processes that lead to muscle wasting.
The researchers will next validate which genes and events the microRNAs actually control in living muscle cells, and investigate whether restoring a healthy balance of microRNAs could be efficient therapy for muscle wasting, as flipping the master switch is more efficient than turning out lights, one by one.
Methicillin-resistant Staph. aureus (MRSA) is among the nearly 200 diseases tracked by HealthMap. This map displays reported U.S. outbreaks of this difficult-to-treat infection as of mid-November.
HealthMap, a Web-based, automated system that monitors disease outbreaks worldwide, began as a weekend project for John Brownstein, PhD, and Clark Freifeld of the Children's Hospital Informatics Program (CHIP). Then, Google.org, Google's philanthropic arm, caught wind of HealthMap and offered $450,000 in grant support—positioning it to become the world's top real-time emerging-disease surveillance site.
Launched in 2006, HealthMap (www.healthmap.org) is accessible to anyone with an Internet connection, public health professionals and visitors alike. Its automated text processing system scans for close to 200 infectious disease categories, from E. coli to Ebola, as well as foodborne, veterinary and agricultural outbreaks. Users can get a quick global view or drill down on local hotspots, clicking on the map for the original reports.
Under the grant, official as of October 1, HealthMap will broaden its reach, hiring translators to mine for data not just in English and Spanish, but in French, Italian, Russian, Chinese and, eventually, Arabic. It will monitor not just news reports and official alerts, like those from the World Health Organization, but also blogs, email listservs and online chat rooms, to detect outbreaks at the earliest possible stage. "Chat rooms provided some of the earliest indications of the 2002’Äì03 SARS outbreak in China," notes Brownstein.
Google's support will also help HealthMap strengthen its filters, screening out "false alarms." A new postdoctoral fellow with expertise in machine learning, Freifeld will help upgrade HealthMap's artificial intelligence tools to capture truly relevant health data. "Once we start monitoring chat rooms and blogs, this system will have to handle a significant amount of noise," he says.
HealthMap has some 50,000 Web users and provides direct feeds to the U.S. Departments of Defense and Health and Human Services. A long-term goal is to open HealthMap to outside infectious-disease experts who can add and edit information, similar to the Wikipedia model.