Navigation Links
Fluorescent proteins illuminating biomedical research

January 25, 2009 (Bronx, NY) Remarkable new tools that spotlight individual cellular molecules are transforming biomedical research. Scientists at the Gruss Lipper Biophotonics Center at the Albert Einstein College of Medicine of Yeshiva University have spearheaded their use in a series of papers, including one published today in the online version of Nature Methods.

These new tools are photoactivatable fluorescent proteins (PAFPs) and other advanced fluorescent proteins (FPs), several of which have been developed by Vladislav Verkhusha, Ph.D., associate professor of anatomy & structural biology at Einstein, and a member of the Biophotonics Center. PAFPs and FPs allow scientists to noninvasively visualize the structures and processes in living cells at the molecular level. It is now possible, for example, to follow cancer cells as they seek out blood vessels and spread throughout the body or to watch how cells manage intracellular debris, preventing premature aging.

These new fluorescent proteins add considerably to the biomedical imaging revolution started by the 1992 discovery that the gene for a green fluorescent protein (GFP) found in a jellyfish could be fused to any gene in a living cell. When the target gene is expressed, GFP lights up (fluoresces), creating a visual marker of gene expression and protein localization, via light (optical) microscopy. Three scientists won The 2008 Nobel Prize in Chemistry for their GFP-related discoveries. Fluorescent proteins of other colors have since been found in marine organisms such as corals.

While this form of imaging is invaluable, it is limited by the inherent nature of optical microscopy, which cannot image details of objects smaller than 200 nanometers or so. However, many cellular structures, which could hold the key to managing or curing disease, are a small fraction of that size ─ just a few nanometers or more.

Using a sophisticated combination of lasers, computers, and highly sensitive digital cameras, scientists have been able to surmount the barriers of optical imaging. The first generation of these new imaging devices, collectively known as super-resolution (SR) fluorescence microscopes, were able to capture images as small as 15 to 20 nanometers the scale of single molecules. But this could be done only in non-living cells. The addition of PAFPs, more versatile versions of FPs, made it possible to do real-time SR fluorescence microscopy in living cells. Last month, Nature Methods selected SR fluorescence microscopy as the 2008 Method of the Year.

Dr. Verkhusha has developed a variety of PAFPs and FPs for use in imaging mammalian cells, expanding the applications of fluorescence microscopy. Among these are PAFPs that can be turned on and off with a pulse of light, FPs that can fluoresce in different colors, and FPs that have better resolution for deep-tissue imaging.

Most recently, Dr. Verkhusha developed a red PAFP called PAmCherry1, which has faster photoactivation, improved contrast, and better stability compared to other PAFPs of its type. "PAmCherry1 will allow improvements in several imaging techniques, notably two-color SR fluorescence microscopy, in which two different molecules or two biological processes can be viewed simultaneously in a single cell," explains Dr. Verkhusha. The findings were published today in the online version of Nature Methods.

Several studies have employed Dr. Verkhusha's PAFPs, revealing new insights into a variety of biological processes. For example, one of his PAFPs was used to capture the first nanoscale images of the orientation of molecules within biological structures. "Such images could be useful in studying protein-protein interactions, the growth and collapse of intracellular structures, and many other biological questions," says Dr. Verkhusha. The results were published in November 2008 in Nature Methods.

In yet another Nature Methods study, also published in November 2008, Dr. Verkhusha contributed a novel PAFP to a new method of viewing individual breast cancer cells for several days at a time, providing new details on how cancer cells invade surrounding tissue and reach blood vessels, a process called metastasis. "Mapping the fate of tumor cells in different regions of a tumor was not possible before the development of the photoswitching technology," explains John Condeelis, Ph.D., co-chair and professor of anatomy and structural biology and co-director of the Gruss Lipper Biophotonics Center.

In addition, Dr. Verkhusha has developed new types of fluorescent proteins for use in conventional fluorescent microscopy. These new fluorescent proteins, called fluorescent timers (FTs), can change their color from blue to red over a matter of hours. "These FTs will enable scientists to study the trafficking of cellular proteins and to provide accurate insight into the timing of intracellular processes, such as activation or inhibition of gene expression or protein synthesis," says Dr. Verkhusha.

Together with another Einstein scientist, Ana Maria Cuervo, M.D., Ph.D., associate professor of developmental & molecular biology, anatomy & structural biology, and medicine, Dr. Verkhusha employed the FTs to demonstrate for the first time how a protein called LAMP-2A, which scavenges cellular debris, is transported to intracellular organelles called lysosomes, where the debris is digested. Understanding this process, which maintains the health of cells and organs, may lead to treatments to keep elderly people's organs in prime condition. The findings were published in the January 11 issue of Nature Chemical Biology.


Contact: Michael Heller
Albert Einstein College of Medicine

Related biology news :

1. Carnegie Mellon scientists develop fluorescent proteins for live cell imaging, biosensor design
2. Fluorescent cells give early warning for eye disease
3. Fluorescent nano-barcodes could revolutionize diagnostics
4. Fantastic photographs of fluorescent fish
5. Researchers create new class of fluorescent dyes to detect reactive oxygen species in vivo
6. Researchers identify proteins involved in new neurodegenerative syndrome
7. NIH awards researcher $1.5 million new innovator grant for fruit-fly studies of prion proteins
8. Depression, aging, and proteins made by a virus may all play role in heart disease
9. New approach builds better proteins inside a computer
10. Legionnaires bacterial proteins work together to survive
11. Proteins pack tighter in crowded native state
Post Your Comments:
(Date:9/30/2015)... YORK , Sept. 30, 2015  The global glucose ... billion for 2015. So says a new report on the ... diabetes management segment dominate the market, followed by continuous glucose ... publisher. Kalorama reports on the market for these products in its ... ...
(Date:9/28/2015)... Sept. 28, 2015 CLEAR, the ... its expedited traveler service is coming to ... travel, bringing a frictionless experience, serious speed ... "CLEAR offers our travelers an expedited ... said Jim Smith , Executive Director, ...
(Date:9/28/2015)... According to a new market ... (Scanner & Others), Application (Access Control & Others), Industry ... Geography Global - Forecast to 2020", published by MarketsandMarkets, the ... Million by 2020, at a CAGR of 23.40% between ... data T ables and 66 Figures ...
Breaking Biology News(10 mins):
(Date:10/13/2015)... Oct. 13, 2015 Applied BioMath ( ... decision points throughout the drug invention process, announced that ... 2015 on October 20-22, 2015 in Boston ... Co-Founder, President, and CEO of Applied BioMath, will present ... research to clinical trials" on Wednesday October 21st 2015 ...
(Date:10/13/2015)... October 13, 2015      Q ... company, has entered into a strategic relationship with Wombat ... and Paris, France based strategic ... --> This collaborative arrangement gives Q BioMed ... advisory team as well as long established pharmaceutical industry ...
(Date:10/13/2015)... ... ... Clinovo recently appointed Jeff Parr and Ed Donaldson to its Business Development Management ... Jeff Parr has spent the past decade providing quality management software and consulting services ... Sciex to name a few. He is based in Salt Lake City, a ...
(Date:10/12/2015)... THOUSAND OAKS, Calif. and BRUSSELS ... and UCB (Euronext Brussels: UCB) today presented additional findings from ... trial. 1 The findings were presented today in an ... Mineral Research (ASBMR) 2015 Annual Meeting in Seattle ... 2 --> The small exploratory sub-study ...
Breaking Biology Technology: