Syndicate content

Archive - May 5, 2013 - Story

Portable Device Provides Rapid, Accurate Diagnosis of TB, Other Bacterial Infections

A handheld diagnostic device that Massachusetts General Hospital (MGH) investigators first developed to diagnose cancer has been adapted to rapidly diagnose infections by Mycobacterium tuberculosis (TB) and other important infectious bacteria. Two papers, one appearing in the journal Nature Communications, and the other in Nature Nanotechnology describe portable devices that combine microfluidic technology with nuclear magnetic resonance (NMR) to not only diagnose these important infections, but also determine the presence of antibiotic-resistant bacterial strains. "Rapidly identifying the pathogen responsible for an infection and testing for the presence of resistance are critical not only for diagnosis but also for deciding which antibiotics to give a patient," says Ralph Weissleder, M.D., Ph.D., director of the MGH Center for Systems Biology (CSB) and co-senior author of both papers. "These described methods allow us to do this in two to three hours, a vast improvement over standard culturing practice, which can take as much as two weeks to provide a diagnosis." Investigators at the MGH CSB previously developed portable devices capable of detecting cancer biomarkers in the blood or in very small tissue samples. Target cells or molecules are first labeled with magnetic nanoparticles, and the sample is then passed through a micro NMR system capable of detecting and quantifying levels of the target. But initial efforts to adapt the system to bacterial diagnosis had trouble finding antibodies – the detection method used in the earlier studies – that would accurately detect the specific bacteria. Instead the team switched to targeting specific nucleic acid sequences. The system described in the Nature Communications paper, published online on April 23, 2013, detects DNA from the tuberculosis bacteria in small sputum samples.

Platyfish Genome Sequenced

The sequence and analysis of the platyfish genome was published in the May 2013 issuee of Nature Genetics. The work represents the first genome sequence of a poeciliid fish and provides insights into evolutionary adaptation in this freshwater fish as well as a potential model for cancer research. Dr. Wesley Warren of the Genome Institue, the Washington University School of Medicine, and an international group of colleagues report the sequencing. The authors use this as a model to examine the evolution of a number of traits, including a live-bearing reproductive mode, pigmentation patterns, cancer, and behavioral traits. They identify a gene implicated in both pigmentation patterning and melanoma development in the platyfish. They also find evidence for selection of genes associated with viviparity—the development of the embryo inside the body of the mother, eventually leading to a live birth. In addition, they identify selective retention of duplicate genes implicated in cognition during the evolution of teleost fish, suggesting a model for the evolution of behavioral complexity in fish. [Press release] [Nature Genetics abstract]

BAF Protein Complex May Play Role in Preventing Many Forms of Cancer

Researchers at the Stanford University School of Medicine have identified a group of proteins that are mutated in about one-fifth of all human cancers. This finding suggests that the proteins, which are members of a protein complex that affects how DNA is packaged in cells, normally work to suppress the development of tumors in many types of tissues. The broad reach of the effect of mutations in the complex, called BAF, rivals that of another well-known tumor suppressor called p53. It also furthers a growing notion that these so-called chromatin-regulatory complexes may function as much more than mere cellular housekeepers. "Although we knew that this complex was likely to play a role in preventing cancer, we didn't realize how extensive it would be," said postdoctoral scholar Cigall Kadoch, Ph.D. "It's often been thought that these complexes play supportive, maintenance-like roles in the cell. But this is really changing now." Dr. Kadoch shares lead authorship of the study with postdoctoral scholar Diana Hargreaves, Ph.D. Gerald Crabtree, M.D., professor of developmental biology and of pathology, is the senior author of the study, which was published online on May 5, 2013 in Nature Genetics. Chromatin-regulatory complexes work to keep DNA tightly condensed, while also granting temporary access to certain portions for replication or to allow the expression of genes necessary for the growth or function of the cell. Members of Dr. Crabtree's laboratory have been interested in BAF complexes and their function for many years. Recently, they reported in the journal Nature that switching subunits within these complexes can convert human fibroblasts to neurons, which points to their instructive role in development and, possibly, cancer.