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Archive - Oct 24, 2015

New Method May Revolutionize Drug Design; Allows Real-Time Detection of Small Molecule-Membrane Protein Binding Kinetics on Single Intact Cells with No Molecular Labeling; Faster, More Precise, Cheaper Kinetics Measurements

Most pharmaceutical drugs consist of small molecules that target a class of proteins found on the surfaces of cell membranes. Studying these subtle interactions is essential for the design of effective drugs, but the task is extremely challenging. Now, Nongjian Tao, Ph.D., and his colleagues at Arizona State University's (ASU’s) Biodesign Institute describe a new method for examining small molecules and their communication with membrane proteins. The research will allow scientists and clinicians to study these interactions at an astonishingly minute scale with unprecedented precision. The new work has broad implications for basic research into biological function at the cellular level, as well as providing an efficient platform for new drug design, which can be carried out more rapidly and precisely, at lower cost. The method permits the first direct, real-time measurement of the binding kinetics of small molecules with membrane proteins on intact cells, without the use of molecular labeling. The study was published in an open-access article in the October 23, 2015 issue of Science Advances. The article is titled “Kinetics of Small Molecule Interactions with Membrane Proteins in Single Cells Measured with Mechanical Amplification.” "Most drugs are small molecules and most drug targets are membrane proteins," says Dr. Tao, who directs ASU’s Biodesign Center for Bioelectronics and Biosensors, which focuses on developing new detection technologies.

New Histone Function Identified: Histone H1 Couples Initiation and Amplification of Ubiquitin Signaling after DNA Damage; Finding May Improve Understanding of DNA Protection & Repair and Spawn New Disease Treatments

Researchers at the University of Copenhagen in Denmark, together with colleagues at the Netherlands Cancer Institute, have identified a previously unknown function of histone H1, one of the five known histones, which allows for an improved understanding of how cells protect and repair DNA damages. This knowledge may eventually result in better treatments for diseases such as cancer. "I believe that there's a lot of work ahead. It's like opening a door onto a previously undiscovered territory filled with lots of exciting knowledge. The histones are incredibly important to many of the cells' processes, as well as their overall well-being," says Dr. Niels Mailand from the Novo Nordisk Foundation Centre for Protein Research at the Faculty of Health and Medical Science. The findings were published online on October 21, 2015 in Nature. The article is titled “Histone H1 Couples Initiation and Amplification of Ubiquitin Signaling after DNA Damage.” Specifically, the researchers concluded that their results “identify histone H1 as a key target of [the E3 ubiquitin ligase RNF8 and the E2 ubiquitin-conjugating enzyme UBC13] RNF8–UBC13 in double-strand break (DSB) signalling and expand the concept of the histone code by showing that post-translational modifications of linker histones can serve as important marks for recognition by factors involved in genome stability maintenance, and possibly beyond.” Histones enable the tight packaging of DNA strands within cells. The strands are approximately two meters in length and the cells are usually approximately 100,000 times smaller. Generally speaking, there are five types of histones. Four of these types are so-called “core” histones, and they are placed like beads on the DNA strands, which are curled up like a ball of yarn within the cells.