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Archive - Jul 23, 2019

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Chemists Find Simplest Organic Molecules Can Self-Assemble to Give Cell-Like Structures Under Early Earth Conditions

Before life began on Earth, the environment likely contained a massive number of chemicals that reacted with each other more or less randomly, and it is unclear how things as complex as cells could have emerged from such chemical chaos. Now, a team led by Tony Z. Jia, PhD, of the Earth-Life Science Institute (ELSI) at the Tokyo Institute of Technology and Kuhan Chandru, PhD, of the National University of Malaysia, has shown that simple α-hydroxy acids, like glycolic and lactic acid (which is used in common store-bought facial peels), spontaneously polymerize and self-assemble into polyester microdroplets when dried at moderate temperatures followed by rehydration, as might have happened along primitive beaches and river banks or in drying puddles. These form a new type of cell-like compartment which can trap and concentrate biomolecules like nucleic acids and proteins. These droplets, unlike most modern cells, are able to easily merge and reform and thus could have hosted versatile early genetic and metabolic systems potentially critical for the origins of life. The new work was published online on July 22, 2019 in PNAS in an article titled “Membraneless Polyester Microdroplets As Primordial Compartments at the Origins of Life.” Scientists from around the world are actively working to understand how life began. All modern Earth life, from bacteria to humans, is made up of cells. Cells are comprised of lipids, proteins, and nucleic acids, with the lipid forming the cell membrane, an enclosure that keeps the other components together and interfaces with the environment, exchanging food and waste. How molecular assemblages as complex as cells originally formed remains a mystery.

Molecular Sensor Scouts DNA Damage and Supervises Repair; Xeroderma Pigmentosa Connection

In the time it takes you to read this sentence, every cell in your body suffers some form of DNA damage. Without vigilant repair, cancer would run rampant, and now scientists at the University of Pittsburgh have gotten a glimpse of how one protein in particular keeps DNA damage in check. According to a study published online on July 22, 2019 in Nature Structural & Molecular Biology, a protein called UV-DDB--which stands for ultraviolet-damaged DNA-binding--is useful beyond safeguarding against the sun. This new evidence points to UV-DDB being a scout for general DNA damage and an overseer of the molecular repair crew that fixes it. The article is titled “Damage Sensor Role of UV-DDB During Base Excision Repair.” "If you're going to fix a pothole, you have to find it first. That's what UV-DDB does. It identifies DNA damage so that another crew can come in and patch and seal it," said study senior author Bennett Van Houten, PhD, Professor of Pharmacology and Chemical Biology at the Pitt School of Medicine and UPMC Hillman Cancer Center. Surveying 3 billion base pairs, packed into a nucleus just a few microns wide, is a tall order, Dr. Van Houten said. Not only is it a lot of material to search through, but it's wound up so tightly that many molecules can't access it. Keeping with the pothole analogy, one possible search strategy is to walk along the road, waiting to step in a hole. Another option is to fly around in a helicopter, but because molecules can't "see," this approach would require frequently landing to look for rough patches. To get around these shortcomings, UV-DDB combines both search strategies. "UV-DDB is like a helicopter that can land and then roll for a couple blocks," Dr. Van Houten said.

Exosomes May Have “Huge Relevance” to Treating & Diagnosing Developmental Brain Disorders; New Work at Scripps Suggests Cellular Cargo Transporters Play Profound Role in Creating Brain Cells & Circuits

Like overpacked suitcases unloaded from the underbelly of a jet, molecular satchels called exosomes are continuously deployed from all cells in the body—many brimming with an assortment of contents that another cell may unpack and use. By sending off these biological parcels, cells communicate with each other via shared proteins and genetic material. Once simply thought to be microscopic sacks of cellular “garbage,” exosomes are now understood to hold immense importance for our health. An outflowing of research in recent years has even shown they can transport molecules that are linked to the spread of cancer and neurodegenerative disorders such as Alzheimer’s. Yet, until recently, their role in brain development has remained a mystery. In new research published online on July 22, 2019 in PNAS, Hollis Cline (photo), PhD, and her colleagues at Scripps Research begin to close that knowledge gap by showing that exosomes are not only integral to the development of neurons and neural circuits, but they can restore health to brain cells affected by developmental disease. The open-access PNAS article is titled “Exosomes Regulate Neurogenesis and Circuit Assembly.” “During different stages of brain development, signaling between cells is absolutely essential,” says Dr. Cline, Co-Chair of the Department of Neuroscience at Scripps Research and Director of the Dorris Neuroscience Center at Scripps. “We found that exosomes are one of the ways cells communicate these signals.” Our bodies use spherical containers called “vesicles” to traffic different materials within and among cells. Exosomes are a type of vesicle tasked specifically with transporting various biological cargo—lipids, proteins, RNA,—from one cell to another. Dr.