In pharmaceutical production, identifying enzyme catalysts that help improve the speed and efficiency of the process can be a major boon. Figuring out exactly why a particular enzyme works so well is an altogether different quest.
Take the cholesterol-lowering drug simvastatin. First marketed commercially as Zocor, the statin drug has generated billions of dollars in annual sales. In 2011, UCLA scientists and colleagues discovered that a mutated enzyme could help produce the much sought-after pharmaceutical far more efficiently than the chemical process that had been used for years — and could do it better than the natural, non-mutated version of the enzyme. But no one quite knew why, until another team of UCLA researchers cracked the mystery. (more…)
ForscherInnen an den Max F. Perutz Laboratories (MFPL) der Universität Wien und der Medizinischen Universität Wien ist ein Durchbruch für das Platynereis-Modellsystem gelungen: Zum ersten Mal beschreiben sie eine Methode, mit der spezifische und vererbbare Mutationen in dieser Spezies erzeugt werden können. Damit rückt dieser marine Wurm in eine exzellente Position, um die Forschung in den Bereichen Neurobiologie, Chronobiologie, evolutionäre Entwicklungsbiologie und Meeresbiologie voranzutreiben. Die Studie sowie ein Überblicksartikel zu den genetischen Methoden, die für Platynereis dumerilii zur Verfügung stehen, sind nicht nur Mai-Highlights des renommierten Fachjournals Genetics, ihnen wurde auch das Titelbild der aktuellen Ausgabe gewidmet.
Auf molekularer Ebene wissen wir von vielen faszinierenden biologischen Phänomenen noch viel zu wenig. Der unscheinbare marine Borstenwurm Platynereis dumerilii stellt für die Erforschung dieser Phänomene einen interessanten Modellorganismus dar: Evolutionär gesehen entwickelte er sich sehr langsam und ist so bestens geeignet, um Vorläufergene und Zelltypen zu analysieren. Er besitzt ein Hormonsystem, das mit jenem der Wirbeltiere vergleichbar ist und er kann große Teile seines Körpers regenerieren. Zudem wird seine Fortpflanzungszeit durch mehrere Uhren gesteuert – ein Merkmal, das wahrscheinlich auch viele andere Organismen aufweisen. Diese Charakteristika machen den Borstenwurm ideal für die Evolutionsforschung, die Chronobiologie und für viele weitere Forschungsgebiete. Da es jedoch bislang keine geeigneten molekularbiologischen Werkzeuge gab, war es sehr schwierig, die Funktionen der Platynereis-Gene in vivo zu analysieren. (more…)
Protein versperrt Zugang zum Zellkern, um Erbgut zu schützen
MolekularbiologInnen der Max F. Perutz Laboratories der Universität Wien und der Medizinischen Universität Wien zeigen in Zusammenarbeit mit Kollegen von der ETH Zürich, wie das Eindringen doppelsträngiger RNA wie beispielsweise viralen Erbgutes in den Zellkern verhindert wird. Während der Immunantwort auf eine Virusinfektion wandert das körpereigene Protein ADAR1 aus dem Kern ins Zytoplasma der Zelle, wo es die Virus-RNA so verändert, dass sich damit keine neuen Viren bilden können. Wie dabei jedoch verhindert wird, dass ADAR1 die virale RNA in den Zellkern bringt – wichtig für den Schutz des menschlichen Erbguts – war bisher völlig unklar. In ihrer Studie in PNAS Plus geben die Wiener und Züricher WissenschaftlerInnen eine erste Antwort auf diese Frage. (more…)
With advancing age, highly-evolved brain circuits become susceptible to molecular changes that can lead to neurofibrillary tangles — a hallmark of Alzheimer’s Disease, Yale researchers report the week of March 17 in the Proceedings of the National Academy of Sciences.
The findings not only help to explain why age is such a large risk factor for Alzheimer’s, but why the higher brain circuits regulating cognition are so vulnerable to degeneration while the sensory cortex remains unaffected. (more…)
Berkeley Researchers Show Expanded Role for Guide RNA in Cas9 Interactions with DNA
The potential is there for bacteria and other microbes to be genetically engineered to perform a cornucopia of valuable goods and services, from the production of safer, more effective medicines and clean, green, sustainable fuels, to the clean-up and restoration of our air, water and land. Cells from eukaryotic organisms can also be modified for research or to fight disease. To achieve these and other worthy goals, the ability to precisely edit the instructions contained within a target’s genome is a must. A powerful new tool for genome editing and gene regulation has emerged in the form of a family of enzymes known as Cas9, which plays a critical role in the bacterial immune system. Cas9 should become an even more valuable tool with the creation of the first detailed picture of its three-dimensional shape by researchers with the Lawrence Berkeley National Laboratory (Berkeley Lab) and the University of California (UC) Berkeley. (more…)
Researchers have sequenced the entire messenger RNA – the “genetic photocopies” – contained in the nucleus of a single cell, a long-anticipated step toward better cancer diagnostics and other medical applications.
Researchers have successfully isolated and sequenced the entire messenger RNA – the “genetic photocopies” – contained in the nucleus of a single brain cell. This research, published in the journal Proceedings of the National Academy of Sciences, will help researchers better understand how organs function in health and disease and provide another stepping stone toward personalized medicine. (more…)
Baltimore, MD— One classical question in developmental biology is how different tissue types arise in the correct position of the developing embryo. While one signaling pathway that controls this process has been well described, unexpected findings from a team led by Carnegie’s Steven Farber reveal the importance of polyunsaturated fatty acid metabolism in this process. It is published online December 12 in Developmental Cell.
Fatty acids serve as sources of energy, the building materials of cellular membranes, and as signals for sending messages between cells. Enzymes are needed to activate free fatty acids so that they are useful for cellular processes. The enzymes that perform this function are called acyl-CoA synthetases, often shortened to ACS. (more…)
A study in Nature Communications finds that an enzyme that edits RNA may loosen the genome’s control over invasive snippets of DNA that affect how genes are expressed. In fruit flies, that newly understood mechanism appears to contribute to differences among individuals such as eye color and life span.
PROVIDENCE, R.I. [Brown University] — The story of why we are all so different goes well beyond the endless mixing and matching of DNA through breeding. A new study in the journal Nature Communications, for instance, reports a new molecular mechanism of individual variation found in fruit flies that uses components operating in a wide variety of species, including humans. (more…)
