Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Carnegie Mellon fluorescent biosensor reveals mechanism critical to immune system amplification

24.04.2012
Using a new fluorescent biosensor they developed, researchers at Carnegie Mellon University have discovered how a key set of immune cells exchange information during their coordinated assault on invading pathogens.

The immune cells, called dendritic cells, are harnessed by cancer vaccines and other therapeutics used to amplify the immune system. The finding, published online March 29 in the journal Angewandte Chemie, marks the first time that scientists have visualized how antigens are transferred in the immune system between dendritic cells.

"Knowing the mechanism behind what's going on in these dendritic cells — how they are talking to each other in order to amplify the immune response — is of fundamental significance," said Marcel P. Bruchez, associate professor of biological sciences and chemistry in the Mellon College of Science.

Dendritic cells are specialized immune cells that search for and capture foreign micro-organisms like bacteria, allergens or viruses. The cells engulf the invading organism and break it down into pieces. The dendritic cell then places these pieces, called antigens, on its cell surface.

When a dendritic cell presents antigens on its surface, it instructs other immune cells to multiply and scour the body in search of the harmful micro-organisms. Dendritic cells also can share antigens with other dendritic cells to boost immune cell activation. While scientists knew that antigens from one dendritic cell could show up in another dendritic cell, they didn't know how those antigens got there.

To determine the precise mechanism by which dendritic cells transfer antigens to each other, the research team used a new pH-biosensor developed at Carnegie Mellon's Molecular and Biosensor Imaging Center (MBIC). The biosensor is made up of two components: a fluorogen activating peptide (FAP), which is genetically expressed in a cell and tagged to a protein of interest, and a dye called a fluorogen, which either glows red or green depending on the pH level of its environment.

"All routes into the cell have characteristic pH profiles," Bruchez said. "Our pH-biosensor allows us to determine whether the tagged protein — in this case a surrogate antigen — is moving through neutral compartments into the cell, or through acidic compartments into the cell. Those sorts of things determine whether the antigen enters the cell through an active endocytic process, a phagocytic process, or a caveolar uptake process."

In the current study, researchers tagged a surrogate antigen on the surface of a dendritic cell with the FAP. They added the pH sensitive dye, causing the FAP antigen to glow green, an indication of a neutral pH. As the antigen and its bound dye passed to a separate dendritic cell, the antigen/FAP complex glowed red, indicating it used an acidic pathway to enter the new cell. This change in pH from neutral to acidic reveals that antigens are passed between cells through an active endocytic process.

"Once it's nibbled by the acceptor cell, the antigen goes through this endocytic pathway where it can potentially then be reprocessed and re-displayed on the surface of the receptor cell," Bruchez said.

The new biosensor's activity is novel, Bruchez said, because it binds to its target with nanomolar affinity, becomes fluorescently activated, and then is carried into the cell under endocytic conditions, reporting on the pH as it goes. The researchers are hopeful that this technology is the first in a platform of targetable environmental sensors. The current biosensor can read out pH, but this approach could be extended to measure calcium or other ion fluctuations in living cells. According to Bruchez, there are many ways that this basic chemical concept can be extended.

In addition to Bruchez, the authors include Anmol Grover, Brigitte F. Schmidt and Alan S. Waggoner from CMU's Molecular Biosensor and Imaging Center, and Russell D. Salter and Simon C. Watkins from the University of Pittsburgh School of Medicine, which has a longstanding program studying dendritic cell biology and vaccine design.

This research was funded by the National Institutes of Health (NIH). MBIC is one of the NIH's National Technology Centers for Networks and Pathways. For more information, visit: http://www.mbic.cmu.edu/.

About Carnegie Mellon University: Carnegie Mellon (www.cmu.edu) is a private, internationally ranked research university with programs in areas ranging from science, technology and business, to public policy, the humanities and the arts. More than 11,000 students in the university's seven schools and colleges benefit from a small student-to-faculty ratio and an education characterized by its focus on creating and implementing solutions for real problems, interdisciplinary collaboration and innovation. A global university, Carnegie Mellon's main campus in the United States is in Pittsburgh, Pa. It has campuses in California's Silicon Valley and Qatar, and programs in Asia, Australia, Europe and Mexico. The university is in the midst "Inspire Innovation: The Campaign for Carnegie Mellon University," which aims to build its endowment, support faculty, students and innovative research, and enhance the physical campus with equipment and facility improvements.

Jocelyn Duffy | EurekAlert!
Further information:
http://www.cmu.edu
http://www.mbic.cmu.edu

More articles from Life Sciences:

nachricht New eDNA technology used to quickly assess coral reefs
18.04.2019 | University of Hawaii at Manoa

nachricht New automated biological-sample analysis systems to accelerate disease detection
18.04.2019 | Polytechnique Montréal

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Explosion on Jupiter-sized star 10 times more powerful than ever seen on our sun

A stellar flare 10 times more powerful than anything seen on our sun has burst from an ultracool star almost the same size as Jupiter

  • Coolest and smallest star to produce a superflare found
  • Star is a tenth of the radius of our Sun
  • Researchers led by University of Warwick could only see...

Im Focus: Quantum simulation more stable than expected

A localization phenomenon boosts the accuracy of solving quantum many-body problems with quantum computers which are otherwise challenging for conventional computers. This brings such digital quantum simulation within reach on quantum devices available today.

Quantum computers promise to solve certain computational problems exponentially faster than any classical machine. “A particularly promising application is the...

Im Focus: Largest, fastest array of microscopic 'traffic cops' for optical communications

The technology could revolutionize how information travels through data centers and artificial intelligence networks

Engineers at the University of California, Berkeley have built a new photonic switch that can control the direction of light passing through optical fibers...

Im Focus: A long-distance relationship in femtoseconds

Physicists observe how electron-hole pairs drift apart at ultrafast speed, but still remain strongly bound.

Modern electronics relies on ultrafast charge motion on ever shorter length scales. Physicists from Regensburg and Gothenburg have now succeeded in resolving a...

Im Focus: Researchers 3D print metamaterials with novel optical properties

Engineers create novel optical devices, including a moth eye-inspired omnidirectional microwave antenna

A team of engineers at Tufts University has developed a series of 3D printed metamaterials with unique microwave or optical properties that go beyond what is...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Revered mathematicians and computer scientists converge with 200 young researchers in Heidelberg!

17.04.2019 | Event News

First dust conference in the Central Asian part of the earth’s dust belt

15.04.2019 | Event News

Fraunhofer FHR at the IEEE Radar Conference 2019 in Boston, USA

09.04.2019 | Event News

 
Latest News

New automated biological-sample analysis systems to accelerate disease detection

18.04.2019 | Life Sciences

Explosion on Jupiter-sized star 10 times more powerful than ever seen on our sun

18.04.2019 | Physics and Astronomy

New eDNA technology used to quickly assess coral reefs

18.04.2019 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>