In a study available online and appearing in the April 12 edition of the journal Nature, researchers at UT Southwestern Medical Center describe how they used a library of small RNA molecules — the first used by a university research center — to identify the genes.
“Chemotherapy is a very blunt instrument,” he said. “It makes people sick, and its effects are very inconsistent. Identifying genes that make chemotherapy drugs more potent at lower doses is a first step toward alleviating these effects in patients.”
The current study tested only isolated cancer cells, so further studies will be needed to determine whether blocking the genes in living animals has the same effect.
The findings were made possible because of a technology that allows scientists to rapidly test how cells react when a given gene is turned off, or “silenced.” The so-called high-throughput employs a series of small plastic dishes, each with 96 wells. Using a robot, researchers place small bits of RNA that can block the function of one gene into each well on the plate. Next, non-small-cell lung cancer cells are placed in each well with the RNA.
The tiny bits of RNA used are called small interfering RNA, or siRNA. In this experiment, four siRNAs targeting a single gene were placed in each well. Overall, the researchers used 84,508 different siRNAs.
Next, the drug paclitaxel was added to each well for two days. By examining the survival of the cells in each well, the researchers determined which genes were involved in affecting the cells’ sensitivity to the drug.
All told, the experiment took more than 150,000 individual pipetting steps over seven weeks to test the drug.
The researchers then re-tested the six genes that showed the most dramatic effect with paclitaxel and tried the same test using the chemotherapy drugs vinorelbine (Navelbine) and gemcitabine (Gemzar), but the results were not as dramatic as those seen for paclitaxel. “Our studies using additional drugs indicate that the genes we uncovered are highly specific for paxlitaxel,” said Dr. Angelique Whitehurst, postdoctoral researcher in cell biology and lead author of the study.
“Being able to do this in human cells, and being able to do it fast — this is very powerful,” Dr. White said. “The idea of the screen was to be able to take advantage of the new generation of technology to silence any gene we want. That’s the power of a genome-wide screen — you go in without any expectations and let the data tell you what’s important.”
The siRNA library was developed by Dharmacon Pharmaceuticals and is commercially available. UT Southwestern is the first academic research institution to publish a study using the library, Dr. White said.
Other UT Southwestern researchers involved in the study were Brian Bodemann, medical and graduate student; Jessica Cardenas, student research assistant; Dr. Luc Girard, assistant professor of pharmacology in the Nancy B. and Jake L. Hamon Center for Therapeutic Oncology Research; Dr. Michael Peyton, research scientist in the Hamon Center; Dr. John Minna, professor of internal medicine and director of the Hamon Center; Dr. Carolyn Michnoff, former instructor of biochemistry; Dr. Weihua Hao, software systems specialist in biochemistry; Dr. Michael Roth, professor of biochemistry; and Dr. Xian-Jin Xie, associate professor of clinical sciences. Dr. Deborah Ferguson of Reata Pharmaceuticals also contributed to the study.
The work was supported by the National Cancer Institute, The Robert A. Welch Foundation, Susan G. Komen Foundation, and the Department of Defense.
Aline McKenzie | EurekAlert!
Resolving the mystery of preeclampsia
21.10.2016 | Universitätsklinikum Magdeburg
New potential cancer treatment using microwaves to target deep tumors
12.10.2016 | University of Texas at Arlington
Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.
"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...
In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.
A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...
By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.
"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...
COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.
In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...
'Ferroelectric' materials can switch between different states of electrical polarization in response to an external electric field. This flexibility means they show promise for many applications, for example in electronic devices and computer memory. Current ferroelectric materials are highly valued for their thermal and chemical stability and rapid electro-mechanical responses, but creating a material that is scalable down to the tiny sizes needed for technologies like silicon-based semiconductors (Si-based CMOS) has proven challenging.
Now, Hiroshi Funakubo and co-workers at the Tokyo Institute of Technology, in collaboration with researchers across Japan, have conducted experiments to...
14.10.2016 | Event News
14.10.2016 | Event News
12.10.2016 | Event News
21.10.2016 | Health and Medicine
21.10.2016 | Information Technology
21.10.2016 | Materials Sciences