Navigation Links
Carnegie Mellon researchers create fluorescent biosensor to aid in drug development

Researchers at Carnegie Mellon University have developed a new fluorescent biosensor that could aid in the development of an important class of drugs that target a crucial class of proteins called G protein-coupled receptors (GPCRs).

"Drugs that target GPCRs make up approximately 30 percent of all pharmaceuticals currently on the market, including some of the most prescribed drugs," said Jonathan Jarvik, the Carnegie Mellon professor who led the effort to develop the GPCR biosensor. "This prevalence makes assays for the receptors a billion dollar industry."

GPCRs are popular drug targets because of the pivotal role they play in cells' chemical communication circuits that are responsible for regulating functions critical to health, including circuits involved in heart and lung function, mood, cognition and memory, digestion and the inflammatory response. Found in the cell membrane, GPCRs interact with molecules responsible for cellular communication such as neurotransmitters and hormones. When one of the receptors encounters such a molecule, it relays a signal across the cell membrane that, in turn, initiates a response. After the response is triggered, the receptor retreats from the membrane into the cell's interior.

To create the GPCR biosensor, the research team used a new technology called fluoromodules. Invented by Carnegie Mellon's Molecular and Biosensor Imaging Center (MBIC), fluoromodules are probes that allow scientists to monitor the activities of individual proteins found in living cells in real-time. The probes are made up of two components: a fluorogen-activating protein (FAP) and a non-fluorescent dye called a fluorogen. The FAP is attached to the protein that is being studied, and the fluorogen is engineered to bind to the FAP. When the two meet, they cast off a glow that can be detected using a variety of methods, alerting researchers to the protein's location and activity. The FAP's fluorescence can be turned on and off by adding or removing the fluorogen, a characteristic that makes the fluoromodules more useful than other fluorescent proteins.

In the current study, which is published in the July issue of the Journal of Biomolecular Screening, Jarvik and colleagues engineered a fluoromodule that would readily determine when GPCR retreats from the cell membrane. The researchers genetically expressed a FAP fused to the beta2 adrenergic receptor (β2AR), a well-studied GPCR that is present in brain, heart, lung and other tissues. When the researchers introduced its associated membrane-impermeant fluorogen, it bound to the FAP-tagged GPCR on the cell surface, emitting a bright fluorescent glow. When the receptor was activated and had retreated into the cell, the fluorescence dimmed.

The new biosensor is notable, Jarvik said, because it looks directly at the receptor and provides what is known as a homogeneous, or mix-and-read, assay that can be scaled to screen large numbers of molecules to identify new drug leads.

The researchers are hopeful that this technology can be generalized across other receptors and cell-surface proteins, and are currently researching its broader applications.


Contact: Jocelyn Duffy
Carnegie Mellon University

Related biology news :

1. Carnegies Doug Koshland elected to National Academy of Sciences
2. Carnegies Chris Field elected to American Academy of Arts & Sciences
3. Carnegie Mellon researchers seek to control blood loss
4. Carnegie Mellons Sanna Gaspard named New Face of Engineering
5. Carnegie Mellon first to measure energy released from a virus during infection
6. Carnegie Mellons John Kitchin receives early career award
7. Carnegie Mellons Philip LeDuc discovers new protein function
8. Carnegie Mellon engineers develop machine that visually inspects and sorts strawberry plants
9. Carnegie Mellon researchers receive grant
10. Carnegie Mellon customizing electric cars for cost-effective urban commuting
11. Carnegie Mellon researchers to develop probes to study cellular GPS
Post Your Comments:
(Date:6/27/2016)... Research and Markets has announced the addition ... to their offering. The report ... to grow at a CAGR of 12.28% during the period 2016-2020. ... in-depth market analysis with inputs from industry experts. The report covers ... The report also includes a discussion of the key vendors operating ...
(Date:6/22/2016)... -- The American College of Medical Genetics and Genomics was once ... one of the fastest-growing trade shows during the Fastest 50 ... Las Vegas . Winners ... each of the following categories: net square feet of paid ... The 2015 ACMG Annual Meeting was ranked 23 out of ...
(Date:6/22/2016)... , June 22, 2016   Acuant ... and verification solutions, has partnered with RightCrowd ... solutions for Visitor Management, Self-Service Kiosks and ... products that add functional enhancements to existing ... corporations and venues with an automated ID ...
Breaking Biology News(10 mins):
(Date:6/27/2016)... , June 27, 2016  Alex,s Lemonade Stand ... that that it will open a state-of-the-art bioinformatics lab, ... cancer research. This announcement comes as Liz Scott ... the National Cancer Moonshot Summit in Washington, ... Biden as a participant and advocate of pediatric cancer ...
(Date:6/27/2016)... 2016  Global demand for enzymes is forecast ... to $7.2 billion.  This market includes enzymes used ... biofuel production, animal feed, and other markets) and ... Food and beverages will remain the largest market ... of products containing enzymes in developing regions.  These ...
(Date:6/27/2016)... 2016 /PRNewswire/ - BIOREM Inc. (TSX-V: BRM) ("Biorem" or "the ... major shareholders, Clean Technology Fund I, LP and Clean ... based venture capital funds which together hold approximately ... fully diluted, as converted basis), that they have entered ... equity holdings in Biorem to TUS Holdings Co. Ltd. ...
(Date:6/27/2016)... , June 27, 2016  Sequenom, Inc. (NASDAQ: ... enabling healthier lives through the development of innovative products ... the United States denied its ... the claims of Sequenom,s U.S. Patent No. 6,258,540 (",540 ... criteria established by the Supreme Court,s Mayo Collaborative Services ...
Breaking Biology Technology: