Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Chemical engineers at UCSB design molecular probe to study disease

07.04.2011
Chemical engineers at UC Santa Barbara expect that their new process to create molecular probes may eventually result in the development of new drugs to treat cancer and other illnesses.

Their work, reported in the journal Chemistry & Biology, published by Cell Press, describes a new strategy to build molecular probes to visualize, measure, and learn about the activities of enzymes, called proteases, on the surface of cancer cells.

Patrick Daugherty, senior author and professor of chemical engineering at UCSB, explained that the probes are effective at understanding proteases involved in tumor metastasis.

"Tumor metastasis is widely regarded as the cause of death for cancer patients," said Daugherty. "It's not usually the primary tumor that causes death. Metastasis is mediated by proteases, like the one we are studying here. These proteases can enable tumor cells to separate and degrade surrounding tissue, and then migrate to sites distant from the primary tumor. The tumor doesn't just fall apart. There are many events that must occur for a tumor to release cancerous cells into the blood stream that can circulate and end up in other tissues such as liver or bone."

The probes allowed the researchers, for the first time, to measure directly the activity of a protease involved in metastasis. They did this by adding their probe into a dish of tumor cells. They then measured the activity of this protease that breaks down collagen –– the single most abundant protein (by mass) in the human body.

"We have immediate plans to use similar probes to effectively distinguish metastatic HER2 positive tumors, one of the most commonly used biomarkers of breast cancer," said Daugherty. "A significant fraction of patients have HER2 positive tumors but we don't know which of those tumors is going to metastasize yet. But our ability to make these probes can allow us to identify which of those HER2 positive tumors have the ability to break down that surrounding tissue, to detach from the primary tumor, and to establish a separate tumor somewhere else in the body."

The authors designed the molecular probe to be recognized by a single protease rather than by the many proteases that are present in human tissues. That is half of the probe. The other half of the probe involves an optical technique used to measure activity. This approach relies upon the use of two engineered fluorescent proteins, derived from marine organisms, that absorb and emit light in a process called FRET, or Forster resonance energy transfer.

To prepare the probes, the researchers introduced a gene that encodes the probe into the bacteria E. coli. Then they produced and purified significant quantities of the probe. All of the information needed for the probe is encoded by a DNA sequence. The probes are easy and inexpensive to produce, as well as easily shared with other researchers.

In addition to studying cancer, similarly constructed probes have ramifications for studying 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 you make these probes, to many systems, makes it attractive," said Daugherty. "We happen to study the activity of this protease and a certain type of tumor cells that are derived from cancer patients. But you could apply this to hundreds of molecules and really develop a working understanding of how groups of proteases function together in cell biology."

In individuals with rheumatoid arthritis, for example, there is increased production of proteases, including the one studied by Daugherty's team. This protease mediates collagen breakdown and joint destruction. "If you've got an enzyme that can chew up collagen and you've got lots of collagen in your joints, then you would expect that you would see more rapid degradation of the joint by those proteases," said Daugherty.

Daugherty's research group has created approximately 25 probes analogous to the one presented in the paper. They are building a panel of about 100 probes and will use this panel to characterize how different proteases function. This investigation could lead to new drug therapies for a variety of diseases.

The first author on the paper is Daugherty's former graduate student, Abeer Jabaiah, who is applying a similar process to another protease involved in tumor metastasis as a postdoctoral fellow in Daugherty's lab. Funding for this work was provided by the National Institutes of Health through the National Cancer Institute's Center of Cancer Nanotechnology Excellence and the National Heart, Lung, and Blood Institute's Program of Excellence in Nanotechnology.

Gail Gallessich | EurekAlert!
Further information:
http://www.ucsb.edu

More articles from Life Sciences:

nachricht Symbiotic bacteria: from hitchhiker to beetle bodyguard
28.04.2017 | Johannes Gutenberg-Universität Mainz

nachricht Nose2Brain – Better Therapy for Multiple Sclerosis
28.04.2017 | Fraunhofer-Institut für Grenzflächen- und Bioverfahrenstechnik IGB

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Fighting drug resistant tuberculosis – InfectoGnostics meets MYCO-NET² partners in Peru

28.04.2017 | Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

 
Latest News

Wireless power can drive tiny electronic devices in the GI tract

28.04.2017 | Medical Engineering

Ice cave in Transylvania yields window into region's past

28.04.2017 | Earth Sciences

Nose2Brain – Better Therapy for Multiple Sclerosis

28.04.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>