Using multiphoton fluorescence microscopy, a technique pioneered at Cornell by physicist Watt W. Webb, researchers have for the first time been able to watch chromosomes change their form in order to activate their genes to synthesize key proteins in fruit fly cells. The advance could be a significant step toward understanding the basic processes that underlie gene expression.
The discovery was the result of cross-disciplinary collaboration between Webb and John Lis, Cornell's Barbara McClintock Professor of Molecular Biology and Genetics. Jie Yao, who recently earned his Ph.D. at Cornell, initiated and facilitated the work.
"This technology will revolutionize the way we see gene expression in organisms," said Lis. "We're watching transcription in real time in living cells."
The research was described in the Aug. 31 issue of the journal Nature.
The team's experiments focused on gene regulatory mechanisms: specifically, what happens in a cell's nucleus when an external stimulus (heat) prompts specific genes to activate, and how those activated genes direct the production of proteins that protect the fly against the stress of heating.
"Whenever a cell is stressed -- bingo, it will produce proteins that will help the cell resist stress," said Webb, Cornell professor of applied physics and the S.B. Eckert Professor in Engineering. The process is triggered by a molecule called heat shock factor (HSF), which interacts with genes to cue the synthesis of new proteins. But this well-known process had never been seen in living cells.
Yao used multiphoton microscopy (MPM) to image living salivary gland tissue of Drosophila (fruit flies). Unlike other methods, which lack penetrating power and can damage the specimen, MPM delivers crisp, clear images, even in thicker tissue samples like Drosophila salivary glands.
The research was ultimately possible thanks to the unique composition of the fruit flies' polytene cells -- giant, multistranded chromosomes with hundreds of sets of the genome instead of the usual two sets in conventional cells. This enlarges the usual nuclear dimensions by about 10 times, making them large enough to image the detail.
The results were stunning. "Within two weeks we had spectacular pictures," said Lis. The images included pictures of the genes (hsp70 genes) that protect flies from the effects of extreme heat. By cranking up the heat, the researchers could activate these genes, and by using fruit flies specifically bred to carry fluorescent proteins on HSF, they could watch the transcription factors in action.
"This is the first time ever that anyone has been able to see in detail, at native genes in vivo, how a transcription factor is turned on, and how it then is activated," said Webb.
Using another method that Webb engineered at Cornell, called fluorescence recovery after photobleaching, the researchers also discovered that HSF activators bind to hsp70 genes much longer than previously thought before being replaced with new HSFs, which raises new questions about the mechanisms of gene transcription.
The technique also may offer a new tool for researchers across the biological sciences. Webb says it marks the success of an interdisciplinary trend that offers new potential for researchers in a variety of fields.
"Interaction between the physical sciences and the life sciences is very powerful," said Webb. "And it's becoming more powerful as a tool for advancing our understanding of the life sciences."
Better understanding transcription in lower organisms will help understand the processes in higher organisms, Yao added. "We hope to push the limits to human cells. That's the goal in the next 20 years."
Press Relations Office | EurekAlert!
Mass spectrometry sheds new light on thallium poisoning cold case
14.12.2018 | University of Maryland
Protein involved in nematode stress response identified
14.12.2018 | University of Illinois College of Agricultural, Consumer and Environmental Sciences
The more objects we make "smart," from watches to entire buildings, the greater the need for these devices to store and retrieve massive amounts of data quickly without consuming too much power.
Millions of new memory cells could be part of a computer chip and provide that speed and energy savings, thanks to the discovery of a previously unobserved...
What if, instead of turning up the thermostat, you could warm up with high-tech, flexible patches sewn into your clothes - while significantly reducing your...
A widely used diabetes medication combined with an antihypertensive drug specifically inhibits tumor growth – this was discovered by researchers from the University of Basel’s Biozentrum two years ago. In a follow-up study, recently published in “Cell Reports”, the scientists report that this drug cocktail induces cancer cell death by switching off their energy supply.
The widely used anti-diabetes drug metformin not only reduces blood sugar but also has an anti-cancer effect. However, the metformin dose commonly used in the...
A research team from the University of Zurich has developed a new drone that can retract its propeller arms in flight and make itself small to fit through narrow gaps and holes. This is particularly useful when searching for victims of natural disasters.
Inspecting a damaged building after an earthquake or during a fire is exactly the kind of job that human rescuers would like drones to do for them. A flying...
Over the last decade, there has been much excitement about the discovery, recognised by the Nobel Prize in Physics only two years ago, that there are two types...
12.12.2018 | Event News
10.12.2018 | Event News
06.12.2018 | Event News
14.12.2018 | Power and Electrical Engineering
14.12.2018 | Physics and Astronomy
14.12.2018 | Physics and Astronomy