Compiled by BioPhotonics staff
WALTHAM, Mass. – A new laser-based
microscopy method allows scientists to decipher basic biology and understand how
diseases related to cellular micromachines occur.
The microscope, developed at Brandeis University, uses lasers
to study the splicing of pre-messenger RNA molecules, an essential process in creating
proteins to sustain advanced organisms such as humans. The splicing process is carried
out by cellular micromachines called spliceosomes. By understanding how the process
works, the researchers hope to find therapies that fix the splicing process in cases
where it does not work properly. Their work appears in the March 11, 2011, issue
of Science (doi: 10.1126/science.1198830).
A custom microscope developed at Brandeis University uses lasers
emitting various wavelengths to illuminate biomolecules and study the assembly of
spliceosomes. Each fluorescent biomolecule is “turned on” by a different
laser, allowing different molecules to be identified and studied simultaneously.
Courtesy of Diana Katherine Hunt.
Because genomic DNA resembles a zip file, which carries a large
amount of information in a small amount of space, splicing a gene allows scientists
to decompress the information so the cell can read it before a particular protein
is made. Scientists have found that the regions of a gene that do not code for proteins,
called introns, often interrupt the regions that do, called exons. They had to remove
the introns so the remaining pieces could be spliced together to form appropriate
To make this happen, a collaboration of scientists from Brandeis,
the University of Massachusetts Medical School and Columbia University spent more
than five years creating a specialized light microscope to watch single protein
molecules and to develop a methodology for studying the proteins in their complex
To view the spliceosome in the act of splicing, the scientists
tagged single yeast components with fluorescent dyes and placed the sample in the
microscope. A laser was used to light up the individual tagged molecules, making
it possible to watch the various stages of the splicing process.
The researchers are also studying the process by which an RNA
copy is made, known as transcription, and processes by which cells change their
shape and move. Their findings can be generally applied to a range of biological
problems that previously were difficult to study.