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Archive - Feb 26, 2017

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New Structural Studies Reveal Workings of a Molecular Pump That Ejects Cancer Drugs

Sometimes cells resist medication by spitting it back out. Cancer cells, in particular, have a reputation for defiantly expelling the chemotherapy drugs meant to kill them. Researchers at The Rockefeller University have shed new light on a molecular pump that makes this possible, by determining its three-dimensional structure, down to the level of atoms. “This molecular machine ejects numerous anticancer agents, as well as other drugs. However, no one understood how it can recognize and remove such an impressive variety of substances,” says lead researcher Dr. Jue Chen, the William E. Ford Professor and head of the Laboratory of Membrane Biology and Biophysics at The Rockefeller. “By examining how this drug resistant pump binds to its cargo before transporting it, we have found an answer,” she adds. The new structures, described online on February 23, 2017 in Cell, could help to guide the development of more effective treatments for cancer and other disorders. The Cell article is titled “Structural Basis of Substrate Recognition by the Multidrug Resistance Protein MRP1.” Known as MRP1, the pump in question was identified in drug-resistant lung cancer cells in 1992. While some cancer cells express an unusual abundance of this protein, it is also common within normal cells. It’s a part of the barrier that protects the brain from infection, and helps export hormones, immune signaling compounds, and other cargo, including unwanted foreign substances. Unfortunately for modern medicine, MRP1 often mistakes useful chemicals, including opiates, antidepressants, and antibiotics, for potentially harmful ones in need of removal. Proteins charged with transportation across a cell’s membrane tend to be picky, accepting only particular types of cargo, in some cases a single molecule.

Research Explains Why Some Individuals Can Have Life-Threatening Illness from Common, Usually Harmless Bacterium; Defect in Innate Immunity Can Be Serious If Not Compensated for by Adaptive Immune Response

As much as we try to avoid it, ¬we are constantly sharing germs with those around us. But even when two people have the same infection, the resulting illnesses can be dramatically different—mild for one person, severe or even life-threatening for the other. Now, new research from The Rockefeller University offers insights into how these differences can arise. Dr. Jean-Laurent Casanova, head of Rockefeller’s St. Giles Laboratory of Human Genetics of Infectious Diseases and Howard Hughes Medical Institute Investigator, led a team of researchers to uncover how two different conditions—a genetic immunodeficiency and delayed acquired immunity—can combine to support a life-threatening infection. In the research, published online on February 23, 2017 in Cell. The Cell article is titled “Human Adaptive Immunity Rescues an Inborn Error of Innate Immunity.” Dr. Casanova and his team focused on the case of an otherwise healthy young girl who developed a life-threatening infection from a very common strain of bacterium. Most of us carry this microbe, known as Staphylococcus aureus, on our skin and in our nostrils. It can cause minor infections (often referred to as “staph infections”), but in some people, it results in severe disease. The Cell article is titled “Human Adaptive Immunity Rescues an Inborn Error of Innate Immunity.” The young girl’s illness was mysterious: she had no known risk factors that would lead her to develop the acute form of the disease, and none of her family members had contracted it. So, Dr. Casanova and his team set out to define the underlying cause of her disease by searching her DNA for mutations that might make her more susceptible to staph disease.

Study Offers Guidance on How to Protect Olive Trees from Being Ravaged by Deadly Bacterial Pathogen

Expert ecologists at the UK-based Centre for Ecology & Hydrology (CEH) have devised a scientific model which could help predict the spread of the deadly Xylella fastidiosa which is threatening to destroy Europe's olive trees. The CEH scientists have created a model which is able to qualitatively and quantitatively predict how the deadly bacterial pathogen may spread, as well as offer guidance on how buffer zones should be arranged to protect uninfected olive trees. The research, published online on February 23, 2017 in the journal Biological Invasions, highlights how Xylella fastidiosa is influenced by a range of insects - including spittlebugs - and the rate at which these vectors contribute to the potential spread of the disease across Europe and beyond. Xylella fastidiosa was once restricted to the Americas, but was discovered near Lecce, Italy, in 2013. Since the initial outbreak, it has invaded over 23,000 hectares of olives in the Apulian Region of southern Italy, and is of great concern throughout the olive production areas of the Mediterranean basin. The new open-access article is titled “Modelling the Spread and Control of Xylella fastidiosa in the Early Stages of Invasion in Apulia, Italy.” The study modelled control zones currently employed in Apulia, Italy, and found that increasing buffer widths decreased infection risk beyond the control zone, but may not stop the spread completely. This was due to the ability of the disease-spreading insects to transport themselves between sites. Lead author Dr. Steven White, a Theoretical Ecologist at the Centre for Ecology & Hydrology, said the model indicates the importance of control strategies reducing the risk of the disease-spreading insects infecting healthy trees through the use of wider buffer zones.