Chemical engineers at the UCSB design molecular probe study disease

Current article ratings:
Patients / public:healthcare Prof:
Chemical engineers at the University of Santa Barbara expect that their new process create molecular probes you can eventually lead to the treatment of cancer and other diseases the development of new drugs.

Their work, reported in the journal chemistry & biology, published by cell press, describes how to visualize a new strategy for the development of molecular probes, fairs and learn more about the activities of enzymes, proteases, called on the surface of cancer cells.

Patrick Daugherty, senior author and Professor of chemical engineering at UCSB, explained that to understand the probes proteases tumor are involved in metastasis.

"Tumor metastases widely regarded as the most common cause of death for cancer patients,", said Daugherty. "It is not usually the primary tumor, the death caused." Metastasis is by Proteases, which teaches, we are studying. These proteases enable the tumor cells to separate and affect surrounding tissue, and then migrate from the primary tumor to distant locations. The tumor will fall apart not only. "There are many events that must occur for a tumor free cancer cells in the bloodstream that end up in other tissues such as liver or bone and can circulate."

The probes allows researchers, for the first time to directly measure the activity of a protease involved in metastasis. They did so by adding their probe into a bowl of tumor cells. You then evaluated the activity of the protease, the collagen - breaks down the single most common protein (percentage by mass) in the human body.

"We have immediate plans, to similar probes use to effectively metastatic HER2 positive tumors, one of the most widely used biomarker for breast cancer, are different," Daugherty said. "A significant proportion of patients have HER2-positive tumors, but we do not know which is these tumors, being still develops." "But our ability, these checkpoints can allows us to identify these HER2 positive tumors have to break the ability, that surrounding tissue, from the primary tumor and to establish a separate tumor elsewhere in the body."

The authors developed the molecular probe are detected by a single protease as by the many proteases that are present in human tissues. This is half of the probe. The other half of the control point uses an optical methods to measure the activity. This approach is dependent on the use of two engineered fluorescent proteins derived from marine organisms that absorb and rays of light in a process known as FRET, or Forster resonance energy transfer.

To prepare the probes, a gene that encodes the probe into the bacterium E. coli led the researcher. Then she produced and purified significant quantities of the probe. All information required for the inspection point by a DNA sequence encodes. The probes are easy and inexpensive to produce, as well as easily with other researchers.

In addition to the study of cancer, similarly constructed probes have implications for the study of Alzheimer's disease, arthritis and connective tissue diseases, bacterial infections, viruses, and many other diseases.

"The fact that you can generalize the concept and the way to many systems, make these checkpoints, makes it attractive," Daugherty said. "We randomly study the activity of the protease and a certain type of tumor cells that are derived from cancer patients." But you this could lead to hundreds of molecules and really a working understanding of how groups of proteases function together in biology cells develop. "

In patients with rheumatoid arthritis, it is, for example, increased production of proteases, including the studied of Daugherty's team. This protease mediates collagen breakdown and joint destruction. "If you have an enzyme, that collagen can chew and you have a lot of collagen in your joints, then you would expect that you would see by these proteases, faster removal of common", Daugherty said.

Daugherty's research group has created analog shown in the paper about 25 probes to the. You build a body of about 100 probes and will characterize use this Panel as different proteases function. This investigation may lead to new drug therapies for a variety of diseases.Daugherty's former graduate student, Abeer Jabaiah, a similar process is the first author on the paper on an other protease tumor metastases involved as postdoctoral fellow in Daugherty's lab is applied. Funding for this work by the national institutes of health by the National Cancer Institute provided's was Center of cancer nanotechnology excellence and the national heart, lung and Blood Institute program of excellence in nanotechnology.

Source:
Gail Gallessich
University of California - Santa Barbara