UMass researchers use FRET to study protein misfolding diseases, receive NIH grant

Three University of Massachusetts-Amherst (UMass Amherst) scientists will study folding and misfolding of secretory proteins in the cell’s protein factory, the endoplasmic reticulum, where misfolding can lead to diseases such as cystic fibrosis and liver cirrhosis. They have also received a four-year, $1.2 million EUREKA grant from the U.S. National Institutes of Health (NIH) to complete this work.

Anne Gershenson and her biochemistry and molecular biology colleagues Daniel Hebert and Lila Gierasch begin pilot studies this month using fluorescence resonance energy transfer (FRET) to observe how individual secretory proteins fold; not only in real cells, but in real time. For this work, they will also use a powerful, new super-resolution fluorescence microscope built by UMass Amherst physicist Jennifer Ross and her students. It provides a clear view of individual molecules with far more precision than was possible using traditional light microscopy.

In using FRET, two differently colored fluorescent dyes that are sensitive to each other, a donor and an acceptor, are introduced into the protein chain as it is made. When these are farther apart in a not-yet-folded protein, the donor emits greener fluorescence. As the protein folds and the two dyes get closer together on the three-dimensional structure, their proximity results in emission of a redder fluorescence. Spectroscopically analyzing the fluorescence allows investigators to precisely track donor-to-acceptor distance changes.

Click to Enlarge

Fluorescence microscope image shows isolated endoplasmic reticula. The cartoon illustrates the proposed experiments by Anne Gershenson and colleagues where FRET (green and red dyes) will be used to monitor the protein structure (blue chain) while it is synthesized and folds inside a single endoplasmic reticulum. (Image courtesy Anne Gershenon)

Further, by introducing the FRET donor and acceptor molecules at slightly different parts of the protein chains in each of hundreds of experiments, Gershenson and colleagues will be able to map protein changes associated with folding in situ, in real time.

“Once we get the system operating with good fluorescence and we become adept at incorporating the FRET dyes, our method should prove useful to other researchers for studying a wide variety of other proteins which are involved in many other disease processes,” she says. “That’s the big promise of this approach, and the challenge.”

Over the three years of the program, NIH has awarded 56 grants totaling $67.4 million to support these highly innovative research projects, which promise big scientific payoffs. Awards announced total $25.2 million to 21 institutions.

Posted by Lee Mather

Follow us on Twitter

Subscribe now to BioOptics World Magazine; It’s free!

Get All the BioOptics World News Delivered to Your Inbox

Subscribe to BioOptics World Magazine or email newsletter today at no cost and receive the latest news and information.

 Subscribe Now
Related Articles

New bioimaging technique offers clear view of nervous system

Scientists at Ludwig-Maximilians University have developed a technique for turning the body of a deceased rodent entirely transparent, revealing the central nervous system in unprecedented clarity....

Fluorescent jellyfish proteins light up unconventional laser

Safer lasers to map your cells could soon be in the offing -- all thanks to the humble jellyfish. Conventional lasers, like the pointer you might use to entertain your cat, produce light by emittin...

Fluorescence microscopy helps provide new insight into how cancer cells metastasize

By using fluorescence microscopy, scientists have discovered an alternate theory on how some cancer cells metastasize.

In vivo imaging method visualizes bone-resorbing cell function in real time

In vivo imaging can visualize sites where osteoclasts (bone-resorbing cells) were in the process of resorbing bone.


Neuro15 exhibitors meet exacting demands: Part 2

Increasingly, neuroscientists are working with researchers in disciplines such as chemistry and p...

Why be free?

A successful career contributed to keeping OpticalRayTracer—an optical design software program—fr...

LASER Munich 2015 is bio-bent

LASER World of Photonics 2015 included the European Conferences on Biomedical Optics among its si...

White Papers

Understanding Optical Filters

Optical filters can be used to attenuate or enhance an image, transmit or reflect specific wavele...

How can I find the right digital camera for my microscopy application?

Nowadays, image processing is found in a wide range of optical microscopy applications. Examples ...



Twitter- BioOptics World

Copyright © 2007-2016. PennWell Corporation, Tulsa, OK. All Rights Reserved.PRIVACY POLICY | TERMS AND CONDITIONS