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Archive - Nov 4, 2012

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New Method Empowers Fluorescent Technology

The ability of fluorescence microscopy to study labeled structures like cells has now been empowered to deliver greater spatial and temporal resolutions that were not possible before, thanks to a new method developed by Beckman Institute faculty member Dr. Gabriel Popescu and Dr. Ru Wang from his research group. Using this method, the researchers were able to study the critical process of cell transport dynamics at multiple spatial and temporal scales and reveal, for the first time, properties of diffusive and directed motion transport in living cells. Dr. Popescu leads the Quantitative Light Imaging Laboratory at Beckman, while Dr. Wang of the lab is first author on the paper reporting the method online on November 2, 2012 in Physical Review Letters. The new approach, called dispersion-relation fluorescence spectroscopy (DFS), labels molecules of interest with a fluorophore whose motion, the researchers write, “gives rise to spontaneous fluorescence intensity fluctuations that are analyzed to quantify the governing mass transport dynamics. These data are characterized by the effective dispersion relation.” That ability to study the directed and diffusive transport characteristics of cellular dispersion through a wide range of temporal and spatial scales is more comprehensive than using just fluorescence microscopy. It provides more information than existing methods, such as fluorescence correlation spectroscopy (FCS), which is widely used for studying molecular transport and diffusion coefficients at a fixed spatial scale.

New Means to Kill Malaria Parasiste

Malaria causes up to 3 million deaths each year, predominantly afflicting vulnerable people such as children under five and pregnant women, in tropical regions of Africa, Asia, and Latin America. Treatments are available for this disease, but the Plasmodium parasite is fast becoming resistant to the most common drugs, and health authorities say they desperately need new strategies to tackle the disease. This new potential treatment uses molecules that interfere with an important stage of the parasite's growth cycle and harnesses this effect to kill them. The impact is so acute it kills ninety per cent of the parasites in just three hours and all those tested in laboratory samples of infected human blood cells, within twelve hours. The research was carried out by chemists at Imperial College London and biological scientists from the research institutions Institut Pasteur and CNRS in France. Their work was published in the the October 9, 2012 issue of PNAS. Lead researcher Dr. Matthew Fuchter, from Imperial College London, said: "Plasmodium falciparum causes 90 per cent of malaria deaths, and its ability to resist current therapies is spreading dramatically. Whilst many new drugs are in development, a significant proportion are minor alterations, working in the same way as current ones and therefore may only be effective in the short term. We believe we may have identified the parasite’s 'Achilles' Heel, using a molecule that disrupts many vital processes for its survival and development." The research has identified two chemical compounds that affect Plasmodium falciparum's ability to carry out transcription, the key process that translates genetic code into proteins. These compounds are able to kill the parasite during the long period of its complex life cycle while it inhabits the blood-stream.

Whitehead Scientists Identify Major Flaw in Standard Approach to Global Gene Expression Analysis

Whitehead Institute researchers report that common assumptions employed in the generation and interpretation of data from global gene expression analyses can lead to seriously flawed conclusions about gene activity and cell behavior in a wide range of current biological research. "Expression analysis is one of the most commonly used methods in modern biology," says Whitehead Member Dr. Richard Young. "So we are concerned that flawed assumptions may affect the interpretation of many biological studies." Much of today's interpretation of gene expression data relies on the assumption that all cells being analyzed have similar total amounts of messenger RNA (mRNA), the roughly 10% of a cell's RNA that acts as a blueprint for protein synthesis. However, some cells, including aggressive cancer cells, produce several times more mRNA than other cells. Traditional global gene expression analyses have typically ignored such differences. "We've highlighted this common assumption in gene expression analysis that potentially affects many researchers," says Dr. Tony Lee, a scientist in Dr. Young's lab and a corresponding author of the article published in the October 26, 2012 issue of Cell. "We provided a concrete example of the problem and a solution that can be implemented by investigators." Members of the Dr. Young lab recently uncovered the flaw while investigating genes expressed in cancer cells expressing high levels of c-Myc, a gene regulator known to be highly expressed in aggressive cancer cells. When comparing cells with high and low c-Myc levels, they were surprised to find very different results using different approaches to gene expression analysis.