Friday, April 22, 2011

Worm Studies Shed Light on Human Cancers

Research in the worm is shedding light on a protein associated with a number of different human cancers, and may point to a highly targeted way to treat them.
 University of Wisconsin-Madison scientists were studying a worm protein called TFG-1, which is present in many cell types but whose exact role had never been understood. The scientists discovered that the protein controls key aspects of the movement, or secretion, of growth factors out of cells.
"TFG-1 has never been implicated in the secretory process before," says Dr. Anjon Audhya, an assistant professor of biomolecular chemistry in the School of Medicine and Public Health. "It turns out that humans carry a very similar protein, and we think it plays the same role in humans as in worms."
Reviewing the scientific literature, the researchers found that the gene encoding TFG in humans is fused to at least three other genes implicated in anaplastic large cell lymphoma, papillary thyroid carcinoma and extraskeletal chondrosarcoma. The fusions occur when two broken or rearranged pieces of DNA combine to form a "chimeric" gene with completely distinct properties.
Audhya's studies of TFG-1 in the worm led him to develop a model that explains how TFG fusions may stimulate cancer in humans. As reported in the current issue of Nature Cell Biology (Advanced Online Publication), he proposes that abnormal levels of growth factor secretion may produce a rich micro-environment that helps tumors form and thrive. "We think certain properties of TFG lead it to be a very effective precursor oncogene," he says.
Normally, a growth factor primed to leave a cell is encompassed by a sac, or vesicle, and then transported from one structure inside the cell to another -- endoplasmic reticulum (ER) to Golgi -- before it leaves the cell and discharges into the extracellular space.
Through their genetic studies, the Wisconsin researchers found that TFG-1 in the worm controls vesicle formation and secretion out of the ER.
"We found TFG-1 lies at the interface between the ER and the Golgi, in a scaffolding structure called the ER exit site, where it regulates the formation of vesicles carrying their critical cargo," Audhya says.
The research revealed the precise location where TFG-1 does its work and the mechanism by which it spurs unchecked activity.
The scientists demonstrated that human TFG also functions at ER exit sites, which contain a characterized scaffolding protein called Sec16, and likely regulates secretion of multiple cargoes out of cells.
"In the case of one fusion gene, TFG-NTRK-1, the concentrated non-stop activity of NTRK-1 at ER exit sites may cause the first steps that can transform a normal cell into a cancer cell," Audhya says.
The TFG fusions offer a direct target for future "designer" therapies.
"If you identified patients who have fusion genes that express chimeric proteins, you could create a drug that affects only those proteins," he says, adding that TFG fusions leading to chimeric proteins do not exist in healthy people.
Excited about the possibility that their basic science investigations may be applied to several areas of clinical medicine, the researchers have also begun studying TFG as it relates to B-cell development and the secretion of antibodies

Functioning Synapse Created Using Carbon Nanotubes: Devices Might Be Used in Brain Prostheses or Synthetic Brains

Engineering researchers the University of Southern California have made a significant breakthrough in the use of nanotechnologies for the construction of a synthetic brain. They have built a carbon nanotube synapse circuit whose behavior in tests reproduces the function of a neuron, the building block of the brain.
The team, which was led by Professor Alice Parker and Professor Chongwu Zhou in the USC Viterbi School of Engineering Ming Hsieh Department of Electrical Engineering, used an interdisciplinary approach combining circuit design with nanotechnology to address the complex problem of capturing brain function.
In a paper published in the proceedings of the IEEE/NIH 2011 Life Science Systems and Applications Workshop in April 2011, the Viterbi team detailed how they were able to use carbon nanotubes to create a synapse.
Carbon nanotubes are molecular carbon structures that are extremely small, with a diameter a million times smaller than a pencil point. These nanotubes can be used in electronic circuits, acting as metallic conductors or semiconductors.
"This is a necessary first step in the process," said Parker, who began the looking at the possibility of developing a synthetic brain in 2006. "We wanted to answer the question: Can you build a circuit that would act like a neuron? The next step is even more complex. How can we build structures out of these circuits that mimic the function of the brain, which has 100 billion neurons and 10,000 synapses per neuron?"
Parker emphasized that the actual development of a synthetic brain, or even a functional brain area is decades away, and she said the next hurdle for the research centers on reproducing brain plasticity in the circuits.
The human brain continually produces new neurons, makes new connections and adapts throughout life, and creating this process through analog circuits will be a monumental task, according to Parker.
She believes the ongoing research of understanding the process of human intelligence could have long-term implications for everything from developing prosthetic nanotechnology that would heal traumatic brain injuries to developing intelligent, safe cars that would protect drivers in bold new ways.
Source: daily science web