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December 11th, 2020

High-Throughput Mapping of Phage Resistance Landscape of Bacteria Offers Avenue to Illuminating “Dark Matter” of Microorganism-Phage Interactions Throughout the Biological World

Scientists are continually searching for new and improved ways to deal with bacteria, be it to eliminate disease-causing strains or to modify potentially beneficial strains. And despite the numerous clever drugs and genetic engineering tools humans have invented for these tasks, those approaches can seem clumsy when compared to the finely tuned attacks waged by phages--the viruses that infect bacteria. Phages, like other parasites, are continually evolving ways to target and exploit their specific host bacterial strain, and in turn, the bacteria are continually evolving means to evade the phages. These perpetual battles for survival yield incredibly diverse molecular arsenals that researchers are itching to study, yet doing so can be tedious and labor-intensive. To gain insight into these defensive strategies, a team led by scientists at the Lawrence Berkeley National Laboratory (Berkeley Lab) has just developed an efficient and inexpensive new method. As reported online on October 13, 2020 in PLOS Biology (https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.30...), the team showed that a combination of three techniques can reveal which bacterial receptors phages exploit to infect the cell, as well as what cellular mechanisms the bacteria use to respond to a phage infection. The open-access article is titled “High-Throughput Mapping of the Phage Resistance Landscape in E. coli.” "Despite nearly a century of molecular work, the underlying mechanisms of phage-host interactions are only known for a few pairs, where the host is a well-studied model organism that can be cultured in a lab," said corresponding author Vivek Mutalik, PhD, a research scientist in Berkeley Lab's Environmental Genomics and Systems Biology (EGSB) Division.

December 10th

Genetics of Vascular Smooth Muscle Cells May Play Key Role in Coronary Artery Disease (CAD); Study Identifies One Gene (MIA3) with Protective Effect in CAD Plaque Formation

Researchers at the University of Virginia (UVA) have shed light on how our genes affect our risk for coronary artery disease, the most common form of heart disease. In addition to identifying gene variants that influence risk, they found that one gene in particular (MIA3) appears to have a protective effect. Doctors may be able to use the findings to identify people at high risk and to develop better treatments and preventative interventions. "Current drugs for coronary artery disease treat the risk factors, such as cholesterol or hypertension," said researcher Mete Civelek (photo), PhD, of UVA's Department of Biomedical Engineering and UVA's Center for Public Health Genomics. "Our studies used a genetic approach to identify the mechanisms in the wall of the blood vessels where the disease actually develops." Heart disease is the most common cause of death in the United States, killing one person every 36 seconds. About 18.2 million Americans have the form known as coronary artery disease, or CAD. The federal Centers for Disease Control and Prevention (CDC) estimates that more than 350,000 Americans died from CAD in 2017. Scientists have known that our risk for CAD is affected by diet, smoking, exercise, and other factors, including family history, but the role of our genes remains poorly understood. To better understand this, Dr. Civelek and his colleagues began by examining cells from 151 ethnically diverse heart donors. These cells, called vascular smooth muscle cells, can prove either beneficial or harmful in the buildup of fatty plaques inside our blood vessels. That buildup, known as atherosclerosis, causes CAD. The researchers examined the smooth muscle cells for 12 different characteristics that influence the stability of the plaque patches.

December 10th

Gene from Ancient Bacterium Helps Ticks Spread Lyme Disease

One of the reasons ticks spread Lyme disease so well goes back to a unique evolutionary event. In an article published in the December 10, 2020 issue of Cell, researchers report that an antibacterial enzyme in ticks, Dae2, protects them from bacteria found on human skin, while still allowing them to harbor Borrelia burgdorferi, the bacterium that causes Lyme disease. Ticks acquired the gene for this enzyme 40 million years ago from an unknown species of ancient bacterium through horizontal gene transfer. The open-access Cell article is titled "Ticks Resist Skin Commensals with Immune Factor of Bacterial Origin." Bacteria exchange DNA with each other all the time, but what's remarkable is that 40 million years ago a gene in bacteria jumped across kingdoms all the way into ticks," says senior author Seemay Chou, PhD, a Professor of Biochemistry at University of California San Francisco (UCSF). "The ticks effectively stole a page out of the bacteria's playbook, repurposing their arsenal to use against them." The relationship between ticks and the Lyme bacterium is an example of symbiosis, where two species live in harmony with one another, and often, one organism benefits from the other without harming it. But Dr. Chou's team found that ticks have a more adversarial relationship with with bacteria found on human skin, and ticks use Dae2--the enzyme stolen from ancient bacteria--as a defense agent to keep them safe. Because the ticks are so well protected against human skin bacteria, they can spread Lyme disease far and wide. However, without Dae2, the whole system falls apart. "When we blocked the enzyme, we found that ticks were actually dying from these bacteria." says Dr. Chou.

Subcompartments Discovered in Peroxisomes; Finding “Requires Us to Rethink Everything We Thought We Knew About Peroxisomes,” Lab Leader Says

In his first year of graduate school, Rice University biochemist Zachary Wright discovered something hidden inside a common piece of cellular machinery that's essential for all higher order life from yeast to humans. What Wright saw in 2015 --subcompartments inside organelles called peroxisomes is described in a study published online on December 4, 2020 in Nature Communications. The open-access article is titled “Peroxisomes Form Intralumenal Vesicles with Roles in Fatty Acid Catabolism and Protein Compartmentalization in Arabidopsis” (https://www.nature.com/articles/s41467-020-20099-y). "This is, without a doubt, the most unexpected thing our lab has ever discovered," said study co-author Bonnie Bartel, PhD, Wright's PhD advisor and a member of the National Academy of Sciences. "This requires us to rethink everything we thought we knew about peroxisomes." Dr.Bartel is the Ralph and Dorothy Looney Professor of BioSciences at Rice. Peroxisomes (https://en.wikipedia.org/wiki/Peroxisome)--are compartments where cells turn fatty molecules into energy and useful materials, like the myelin sheaths that protect nerve cells. In humans, peroxisome dysfunction has been linked to severe metabolic disorders, and peroxisomes may have wider significance for neurodegeneration, obesity, cancer, and age-related disorders. Much is still unknown about peroxisomes, but their basic structure--a granular matrix surrounded by a sack-like membrane--wasn't in question in 2015. Dr. Bartel said that's one reason Wright's discovery was surprising. "We're geneticists, so we're used to unexpected things. But usually they don't come in Technicolor," she said, referring to another surprising aspect of Wright's find: beautiful color images that show both the walls of the peroxisome subcompartments and their interiors.

December 9th

Neuropeptide Discoveries in Cockroach Could Be Targets for Someday Defeating Dreaded Pest

Cockroaches are notorious for their abilities to survive and reproduce, much to humanity's chagrin. In addition to scurrying around at night, feeding on human and pet food, and generating an offensive odor, the pests can transmit pathogens and cause allergic reactions. Now, in an article published online on November 9, 2020 in the American Chemical Society’s Journal of Proteome Research, scientists have reported identifying 36 neuropeptides produced by the American cockroach (Periplaneta americana) that could someday be targeted by new, more selective and effective pesticides. The article is titled “Genomics- and Peptidomics-Based Discovery of Conserved and Novel Neuropeptides in the American Cockroach.” Neuropeptides are small proteins produced by neurons or endocrine cells that send messages to other cells. In insects, neuropeptides often act as neurotransmitters, hormones, or growth factors, influencing an organism's development, growth, metabolism, behavior, and reproduction. Therefore, disrupting these processes by targeting neuropeptides or their receptors is a potential new approach to pest control. Recently, Na Li, PhD, of the Guangdong Provincial Key Laboratory of Insect Developmental Biology and Applied Technology, Institute of Insect Science and Technology, School of Life Sciences, South China Normal University, Guangzhou, China, and colleagues determined the genome sequence of P. americana. In the current work, they wanted to use this sequence, combined with peptide analysis, to characterize the neuropeptides of the American cockroach and study how their expression varies by tissue, developmental stage, and sex.

Non-Hallucinogenic Analog of Psychedelic Ibogaine May Have Potential to Treat Addiction, Depression, Other Psychiatric Disorders

A non-hallucinogenic version of the psychedelic drug ibogaine, with potential for treating addiction, depression, and other psychiatric disorders, has been developed by researchers at the University of California (UC), Davis, and colleagues. A paper describing the work was published online on December 9, 2020 in Nature. The article is titled “A Non-Hallucinogenic Psychedelic Analogue with Therapeutic Potential.” "Psychedelics are some of the most powerful drugs we know of that affect the brain," said David Olson, PhD, Assistant Professor of Chemistry at UC Davis and senior author on the paper. "It's unbelievable how little we know about them." Ibogaine is extracted from the plant Tabernanthe iboga (image). There are anecdotal reports that it can have powerful anti-addiction effects such as reducing drug cravings and preventing relapse. But there are also serious side-effects, including hallucinations and cardiac toxicity, and the drug is a Schedule 1 controlled substance under U.S. law. Dr. Olson's laboratory at UC Davis is one of a few in the U.S. licensed to work with Schedule 1 substances. His group set out to create a synthetic analog of ibogaine which retained therapeutic properties without the undesired effects of the psychedelic compound. Dr. Olson's team worked through a series of similar compounds by swapping out parts of the ibogaine molecule. They engineered a new, synthetic molecule which they named tabernanthalog or TBG. Unlike ibogaine, the new molecule is water-soluble and can be synthesized in a single step. Experiments with cell cultures and zebrafish show that it is less toxic than ibogaine, which can cause heart attacks and has been responsible for several deaths.

Targeting T Cell Protein (OCA-B) Might Prevent Type 1 Diabetes, Study Suggests

Researchers at the University of Utah School of Medicine have identified a potential new therapeutic target for the treatment of patients with type 1 diabetes. The study, which was published December 9, 2020 in the Journal of Experimental Medicine (JEM), reveals that inhibiting a protein called OCA-B protects mice from type 1 diabetes by limiting the activity of immune cells that would otherwise destroy the pancreas' insulin-producing β cells (https://rupress.org/jem/article/218/3/e20200533/211581/Targeting-transcr...). The open-access article is titled “Targeting Transcriptional Coregulator OCA-B/Pou2af1 Blocks Activated Autoreactive T Cells in the Pancreas and Type 1 Diabetes.” Type 1 diabetes is an autoimmune disease in which the body's immune system mistakenly attacks pancreatic β cells, cutting off the production of insulin. Patients require life-long insulin therapy to maintain appropriate blood glucose levels. At present, there are no treatments that can prevent the immune system from targeting β cells while preserving its ability to fight infection. White blood cells called T cells can recognize specific molecules produced by invading bacteria and viruses. When T cells encounter these molecules, known as antigens, they turn on hundreds of genes that allow them to fight the infection. A protein called OCA-B binds to many of these genes and helps ensure that they can easily be reactivated if the T cells reencounter the same antigens at a later date. In many autoimmune diseases, T cells mistakenly recognize and respond to antigens produced by normal, healthy cells.

December 8th

Hopkins Scientists Develop Potential Antibiotic for Deadly Drug-Resistant Pathogen (M. abscessus) Related to Tuberculosis Pathogen; M. abscessus Often Lethal in Cystic Fibrosis & Other Lung Ailments

Scientists from Johns Hopkins University and Medicine have developed a possible new antibiotic for a pathogen that is notoriously resistant to medications and frequently lethal for people with cystic fibrosis and other lung ailments. The pathogen, called Mycobacterium abscessus, is related to a better-known bacterium that causes tuberculosis and leprosy, but has recently emerged as a distinct species presenting most often as a virulent lung infection. The team of scientists from the Hopkins Krieger School of Arts & Sciences' Department of Chemistry and the School of Medicine's infectious diseases department published its findings online on December 7, 2020 in Communications Biology. The open-access article is titled “Development of a Penem Antibiotic Against Mycobacteroides abscessus.” The team has developed one of the first potential treatments of a bacterium that has no FDA-approved treatments and a cure rate less than 50%. Before the new antibiotic, called T405, can move closer to becoming a clinical treatment, researchers need to improve its pharmacological potency using a preclinical animal model of the infection. "People die of this in our hospitals every week," said Craig Townsend, PhD, a Professor of Chemistry, who served as a principal investigator on the study, along with Gyanu Lamichhane, PhD, an Associate Professor of Medicine. "The data we have is very promising." Despite years of urgent calls for more studies to understand M. abscessus bacteria and to explore possible treatments, researchers have been wary of experimenting with the most dangerous member of its Non-Tuberculosis Mycobacteria (NTM) family. "It's still considered an emerging disease," Dr. Lamichhane said. "There are now more NTM than tuberculosis cases in the United States.

December 4th

Europe’s EVerZom Raises $1.4 Million to Industrialize Its Exosome Biomanufacturing Platform; Paris Company’s Ambition Is to Transform Regenerative Medicine and Biotherapeutics Using These “Super” Biological Nanoparticles

On December 1, 2020, EVerZom (http://www.everzom.com), a biopharmaceutical company specialized in the bioproduction of exosomes and headquartered in Paris, France, announced that it has raised €1.1 million (~$1.48 million) in funding from institutional and private investors to develop its exosome bioproduction platform. This funding will speed up the platform development and scale-up, with the objective to allow routine clinical grade production by 2022. Exosomes are biological nanoparticles released by cells as an intercellular communication system to transport biomolecules. Exosomes have the ability to deliver therapeutics or regenerate tissue in several pathologies, including osteoarthritis, heart failure, and liver and kidney diseases, conditions which impact more than 150 million patients worldwide. Exosomes are now considered one of the safest and most promising future regenerative therapy solutions. They are also easy to store and have a low immunogenic profile, thus reinforcing their potential. Increasingly, academic and industrial players are working on the therapeutic potential of exosomes. The main obstacle to the translation of exosomes into clinical development is industrial manufacturing, while maintaining robust quality and reproducibility. EVerZom's proprietary innovation consists in applying turbulence stimulation on cells to trigger massive exosome release. This approach enables the production of ten times more exosomes ten times more rapidly than classical methods. The technology is being developed and already implemented in GMP-certified systems, simplifying the clinical transfer. This technology and the know-how developed around exosomes allows EVerZom to offer a scalable and reproducible exosome production process with robust quality controls.

November 28th

Early Detection of Over 50 Cancers Via One-Draw Blood Test--GRAIL and UK Government Partner to Make Revolutionary GRAIL “Galleri” Test Available to Patients; Potential to Reduce UK Cancer Deaths by 20%; Planned Commercially Availability in USA in 2021

On November 26, 2020, GRAIL, Inc. (https://grail.com/), a California-based healthcare company whose mission is to detect cancer early, when it has a much greater likelihood of being be cured, announced a partnership with the United Kingdom’s (UK) National Health Service (NHS) to help transform cancer outcomes by making GRAIL’s multi-cancer early detection blood test, Galleri™ (https://grail.com/galleri/), available to UK patients starting in 2021. The commercial partnership program aims to confirm Galleri’s clinical and economic performance in the NHS system as a precursor to its routine use by the NHS. The partnership program will involve approximately 165,000 people in the UK and includes two groups. The first will include 140,000 people over the age of 50 without any suspicion of cancer, and the second will include 25,000 people aged 40 and above with suspicious signs or symptoms of cancer. Based on data from this program, access to the test could be expanded to approximately one million people across 2024 and 2025 and may be rolled out to a larger population thereafter. In a clinical validation study in the U.S., an earlier version of Galleri detected over 50 types of cancer with a low false-positive rate of less than 1% through a single blood draw. Modeling data show that adding Galleri to existing standard of care has the potential to decrease the number of cancers diagnosed at late stage by nearly half, which could reduce the total number of cancer deaths in the UK by approximately one-fifth. “Every year, nearly 200,000 people in the UK die from cancer. Many of these people are diagnosed too late for treatment to be effective,” said Lord David Prior, Chair of NHS England.