'Looking' At Eyeless From Two Directions

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'Looking' At Eyeless From Two Directions

http://www.medicalnewstoday.com/medicalnews.php?newsid=39170

HOUSTON -- (March, 2006) - When Dr. Rui Chen, assistant professor in

the Baylor College of Medicine Human Genome Sequencing Center, sought

to understand further the protein called Eyeless, he faced a dilemma.

Eyeless is a transcription factor, which means one of its major

activities is to turn off or turn on other genes that have an effect

on eye development later in the process. It is so powerful that when

it is inserted into almost any tissues of the fruit fly, eyes grow -

often in unexpected places.

Because Eyeless is a critical factor in the development of eyes in

fruit flies or Drosophila, (a common model organism for studying how

different organs grow), understanding the genes it affects could

offer key clues into how the organs for sight actually develop in

fruit flies and ultimately people.

One method for locating these genes is called a microarray, a tiny

DNA chip used to identify specific sequences of genetic material. A

microarray can provide hundreds of candidate genes - too many to be

useful. Another method is to use bioinformatics and computers to

predict where transcription factors bind, but this can give thousands

of candidate genes. Again, that's too much information to be

valuable.

Chen, however, took a different tack. He used both methods. Then he

dealt with only the genes and binding sequences that were found by

both. Of the 300 genes found by microarray and 10,000 or more by the

binding site technique, only 21 were found by both.

Because 11 of these were known to play a key role in eye development,

he knew he was on the right track. A report of his work appears

online today in the journal Genome Research.

" The reason I like this project is that it provides the possibility

of doing this in almost any species, " said Chen. " It's a combination

of genomic and biologic techniques. "

" Finding specific targets of a transcription factor is the Holy Grail

for many biologists, " said Dr. Graeme Mardon, senior co-author and a

professor in the Program in Developmental Biology at BCM. In this

case, he said, the researchers have shown that the genes they found

are, in fact, targets of the Eyeless protein.

" We are now in the process of knocking out hundreds of genes

predicted to be targets of this retinal network, " said Mardon. " This

has opened the door to determining what are the critical targets of

this gene for eye development. Others can use similar methods to do

the same thing. "

Eventually, he said, the technique could be used to identify genes

that are involved in similar processes that go wrong, leading to

diseases. This will identify the areas where things go wrong so that

researchers can target proposed therapies and drugs in the future.

In their area, the technique speeds the process of identifying those

genes that are really important in identifying the genes critical to

development of the eye.

" It also gives you a global picture of what the transcription factor

does, " said Chen. " This is also a molecular screen " that will be

valuable in studying mammals.

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Funding for this project came from the National Eye Institute, the

Retina Research Foundation, the Curtis & Doris K. Hankamer Foundation

and The and Janice McNair Foundation.