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 Catalysts for climate protection
19.08.2019 | Fraunhofer-Institut für Grenzflächen- und Bioverfahrenstechnik IGB

nachricht From the tiny testes of flies, new insight into how genes arise
19.08.2019 | Rockefeller University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: A miniature stretchable pump for the next generation of soft robots

Soft robots have a distinct advantage over their rigid forebears: they can adapt to complex environments, handle fragile objects and interact safely with humans. Made from silicone, rubber or other stretchable polymers, they are ideal for use in rehabilitation exoskeletons and robotic clothing. Soft bio-inspired robots could one day be deployed to explore remote or dangerous environments.

Most soft robots are actuated by rigid, noisy pumps that push fluids into the machines' moving parts. Because they are connected to these bulky pumps by tubes,...

Im Focus: Vehicle Emissions: New sensor technology to improve air quality in cities

Researchers at TU Graz are working together with European partners on new possibilities of measuring vehicle emissions.

Today, air pollution is one of the biggest challenges facing European cities. As part of the Horizon 2020 research project CARES (City Air Remote Emission...

Im Focus: Self healing robots that "feel pain"

Over the next three years, researchers from the Vrije Universiteit Brussel, University of Cambridge, École Supérieure de Physique et de Chimie Industrielles de la ville de Paris (ESPCI-Paris) and Empa will be working together with the Dutch Polymer manufacturer SupraPolix on the next generation of robots: (soft) robots that ‘feel pain’ and heal themselves. The partners can count on 3 million Euro in support from the European Commission.

Soon robots will not only be found in factories and laboratories, but will be assisting us in our immediate environment. They will help us in the household, to...

Im Focus: Scientists create the world's thinnest gold

Scientists at the University of Leeds have created a new form of gold which is just two atoms thick - the thinnest unsupported gold ever created.

The researchers measured the thickness of the gold to be 0.47 nanometres - that is one million times thinner than a human finger nail. The material is regarded...

Im Focus: Study on attosecond timescale casts new light on electron dynamics in transition metals

An international team of scientists involving the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) in Hamburg has unraveled the light-induced electron-localization dynamics in transition metals at the attosecond timescale. The team investigated for the first time the many-body electron dynamics in transition metals before thermalization sets in. Their work has now appeared in Nature Physics.

The researchers from ETH Zurich (Switzerland), the MPSD (Germany), the Center for Computational Sciences of University of Tsukuba (Japan) and the Center for...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

The power of thought – the key to success: CYBATHLON BCI Series 2019

16.08.2019 | Event News

4th Hybrid Materials and Structures 2020 28 - 29 April 2020, Karlsruhe, Germany

14.08.2019 | Event News

What will the digital city of the future look like? City Science Summit on 1st and 2nd October 2019 in Hamburg

12.08.2019 | Event News

 
Latest News

Stanford builds a heat shield just 10 atoms thick to protect electronic devices

19.08.2019 | Information Technology

Researchers demonstrate three-dimensional quantum hall effect for the first time

19.08.2019 | Physics and Astronomy

Catalysts for climate protection

19.08.2019 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>