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Archive - Aug 23, 2013

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New Approach Provides Unprecedented Control of Genome Editing in Flies; Promises Insight into Human Development, Disease

In an era of widespread genetic sequencing, the ability to edit and alter an organism's DNA is a powerful way to explore the information within and how it guides biological function. A paper from the University of Wisconsin–Madison (UW-Madison) published as an open-access article in the August 2013 issue of the journal GENETICS takes genome editing to a new level in fruit flies, demonstrating a remarkable level of fine control and, importantly, the transmission of those engineered genetic changes through generations. Both features are key for driving the utility and spread of an approach that promises to give researchers new insights into the basic workings of biological systems, including embryonic development, nervous system function, and the understanding of human disease. "Genome engineering allows you to change gene function in a very targeted way, so you can probe function at a level of detail" that wasn't previously possible, says Dr. Melissa Harrison, an assistant professor of biomolecular chemistry in the UW–Madison School of Medicine and Public Health and one of the three senior authors of the new study. Disrupting individual genes has long been used as a way to study their roles in biological function and disease. The new approach, based on molecules that drive a type of bacterial immune response, provides a technical advance that allows scientists to readily engineer genetic sequences in very detailed ways, including adding or removing short bits of DNA in chosen locations, introducing specific mutations, adding trackable tags, or changing the sequences that regulate when or where a gene is active. The approach used in the new study, called the CRISPR RNA/Cas9 system, has developed unusually quickly.

Gold Standard for Damage-Free Delivery of Drugs or Biosensors to Cell Interior

Cells are very good at protecting their precious contents — and, as a result, it’s very difficult to penetrate their membrane walls to deliver drugs, nutrients, or biosensors without damaging or destroying the cell. One effective way of doing so, discovered in 2008, is to use nanoparticles of pure gold, coated with a thin layer of a special polymer. But nobody knew exactly why this combination worked so well, or how it made it through the cell wall. Now, researchers at MIT and the Ecole Polytechnique de Lausanne in Switzerland have figured out how the process works, and the limits on the sizes of particles that can be used. Their analysis was published online on August 5, 2013 in the journal Nano Letters, in a paper by graduate students Reid Van Lehn, Prabhani Atukorale, Yu-Sang Yang, and Randy Carney, and professors Alfredo Alexander-Katz, Darrell Irvine, and Francesco Stellacci. Until now, says Van Lehn, the paper’s lead author, “the mechanism was unknown. … In this work, we wanted to simplify the process and understand the forces” that allow gold nanoparticles to penetrate cell walls without permanently damaging the membranes or rupturing the cells. The researchers did so through a combination of lab experiments and computer simulations. The team demonstrated that the crucial first step in the process is for coated gold nanoparticles to fuse with the lipids — a category of natural fats, waxes, and vitamins — that form the cell wall. The scientists also demonstrated an upper limit on the size of such particles that can penetrate the cell wall — a limit that depends on the composition of the particle’s coating. The coating applied to the gold particles consists of a mix of hydrophobic and hydrophilic components that form a monolayer — a layer just one molecule thick — on the particle’s surface.