Nanotechnology Now

Our NanoNews Digest Sponsors

Heifer International

Wikipedia Affiliate Button

Home > Press > Chemical Engineers at UCSB Design Molecular Probes to Study Disease

Enhanced detection of
endogenous protease activity.
Image: Abeer Jabaiah
Enhanced detection of endogenous protease activity. Image: Abeer Jabaiah

Abstract:
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.

Chemical Engineers at UCSB Design Molecular Probes to Study Disease

Santa Barbara, CA | Posted on April 6th, 2011

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.

####

For more information, please click here

Contacts:
Gail Gallessich

(805) 893-7220

George Foulsham

(805) 893-3071

Copyright © UCSB

If you have a comment, please Contact us.

Issuers of news releases, not 7th Wave, Inc. or Nanotechnology Now, are solely responsible for the accuracy of the content.

Bookmark:
Delicious Digg Newsvine Google Yahoo Reddit Magnoliacom Furl Facebook

Related News Press

News and information

Basque researchers turn light upside down February 23rd, 2018

Stiffness matters February 23rd, 2018

Imaging individual flexible DNA 'building blocks' in 3-D: Berkeley Lab researchers generate first images of 129 DNA structures February 22nd, 2018

'Memtransistor' brings world closer to brain-like computing: Combined memristor and transistor can process information and store memory with one device February 22nd, 2018

Chemistry

Ultra-efficient removal of carbon monoxide using gold nanoparticles on a molecular support: New method and mechanism for state-of-the-art gas purification February 9th, 2018

Fast-spinning spheres show nanoscale systems' secrets: Rice University lab demonstrates energetic properties of colloids in spinning magnetic field February 7th, 2018

New filters could enable manufacturers to perform highly-selective chemical separation January 23rd, 2018

Nanowrinkles could save billions in shipping and aquaculture Surfaces inspired by carnivorous plants delay degradation by marine fouling January 17th, 2018

Govt.-Legislation/Regulation/Funding/Policy

Imaging individual flexible DNA 'building blocks' in 3-D: Berkeley Lab researchers generate first images of 129 DNA structures February 22nd, 2018

'Memtransistor' brings world closer to brain-like computing: Combined memristor and transistor can process information and store memory with one device February 22nd, 2018

Arrowhead Receives Regulatory Clearance to Begin Phase 1 Study of ARO-AAT for Treatment of Alpha-1 Liver Disease February 22nd, 2018

Computers aid discovery of new, inexpensive material to make LEDs with high color quality February 20th, 2018

Molecular Nanotechnology

Moving nanoparticles using light and magnetic fields January 25th, 2018

Piecework at the nano assembly line: Electric fields drive nano-motors a 100,000 times faster than previous methods January 22nd, 2018

'Gyroscope' molecules form crystal that's both solid and full of motion: New type of molecular machine designed by UCLA researchers could have wide-ranging applications in technology and science January 16th, 2018

Going swimmingly: Biotemplates breakthrough paves way for cheaper nanobots: By using bacterial flagella as a template for silica, researchers have demonstrated an easier way to make propulsion systems for nanoscale swimming robots November 30th, 2017

Nanomedicine

Stiffness matters February 23rd, 2018

Histology in 3-D: New staining method enables Nano-CT imaging of tissue samples February 22nd, 2018

Imaging individual flexible DNA 'building blocks' in 3-D: Berkeley Lab researchers generate first images of 129 DNA structures February 22nd, 2018

Arrowhead Receives Regulatory Clearance to Begin Phase 1 Study of ARO-AAT for Treatment of Alpha-1 Liver Disease February 22nd, 2018

Discoveries

Basque researchers turn light upside down February 23rd, 2018

Histology in 3-D: New staining method enables Nano-CT imaging of tissue samples February 22nd, 2018

Developing reliable quantum computers February 22nd, 2018

Imaging individual flexible DNA 'building blocks' in 3-D: Berkeley Lab researchers generate first images of 129 DNA structures February 22nd, 2018

Announcements

Basque researchers turn light upside down February 23rd, 2018

Stiffness matters February 23rd, 2018

Histology in 3-D: New staining method enables Nano-CT imaging of tissue samples February 22nd, 2018

Developing reliable quantum computers February 22nd, 2018

NanoNews-Digest
The latest news from around the world, FREE



  Premium Products
NanoNews-Custom
Only the news you want to read!
 Learn More
NanoStrategies
Full-service, expert consulting
 Learn More











ASP
Nanotechnology Now Featured Books




NNN

The Hunger Project