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Archive - 2018 - Story

February 12th

Researchers in Sweden Create Gold-Treated DNA Wires 100 Times More Sensitive Than Other Biosensors

On February 12, 2018, scientists in Sweden reported a nanoengineering innovation that offers hope for treatment of cancer, infections, and other health problems –i.e., conductive wires of DNA enhanced with gold which could be used to electrically measure hundreds of biological processes simultaneously. While DNA nanowires have been in development for some time, the method developed at KTH Royal Institute of Technology and Stockholm University produces a unique three-dimensional biosensor for better effectiveness than flat, two-dimensional sensors. “Our geometry makes it much easier to measure several biomolecules simultaneously, and is also 100 times more sensitive,” says KTH Professor Wouter van der Wijngaart. “This is the first out-of-plane metallic nanowire formation based on stretching of DNA through a porous membrane,” Professor van der Wijngaart says. The DNA nanowires, treated with gold to make them conductive, are created only in the presence of specific biomarker molecules in the patient sample and transmit evidence of the biomarker presence, even when such molecules are low in concentration. The conductive wires short-circuit both sides of the membrane, which makes them easy to detect. To make the wires, the team first captured molecules, on the surface of a porous membrane, which were designed to only bind with specific biomarker molecules in the sample. Such molecular binding events then trigger the formation of long DNA wires that are drawn through the pores by vacuum drying. Then the membrane is treated with a solution of nanometer-sized gold particles, which can only bind to DNA molecules in a certain sequence, Professor van der Wijngaart says. The researchers published their results online on February 12, 2018 in Microsystems and Nanoengineering (Nature Publishing Group).

February 11th

Bonnie J. Addario Lung Cancer Foundation Awards $100,000 to Winners of “Lung Cancer Early Detection Challenge: Concept to Clinic”—Crowdsourcing Challenge Designed to Accelerate Delivery of Artificial Intelligence (AI) to the Clinic

On February 6, 2018, the Bonnie J. Addario Lung Cancer Foundation (ALCF), headquartered in San Carlos, California, announced that Willi Gierke, an IT systems engineering student, will receive more than $30,000 as the leader in points in the “Lung Cancer Early Detection Challenge: Concept to Clinic.” Gierke, a master’s student at the Hasso Plattner Institute in Potsdam, Germany, and more than 600 contributors from around the world have been working in a collaborative fashion to create open-source software with the goal of building out artificial intelligence (AI) that will help lung cancer patients live longer. “The focus of the challenge was to make artificial intelligence advances useful, not just for data scientists interested in cutting-edge methods, but for clinicians working on the front lines of lung cancer detection and the patients they serve,” said Bonnie J. Addario, a 14-year lung cancer survivor and ALCF founder. “My hope is that the winners of this challenge continue the momentum of this exciting project to help radiologists detect lung cancer earlier and save lives.” During the challenge, run by DrivenData ( in partnership with ALCF, contributors used input from patients and radiologists to build out state-of-the-art algorithms applied to the detection and assessment of individual nodules from CT scans. Throughout the competition, a technical panel of experts awarded points and prizes to data scientists, engineers, User Interface (UI) developers, and coders based on how valuable their submissions were to the project in the different areas of need: AI-powered prediction models, back-end engineering, front-end design implementation, and community development.

Scientists ID Biomarkers for Cancer Survival Protein HSP70; Will Enable Studies of Small Molecules That Inhibit Hsp70 In Artificial Environments and Begin Testing Ways to Develop These Molecules into Cancer Therapeutics

A recent study from the University of Michigan (U-M) Life Sciences Institute and the University of California, San Francisco (UCSF), has opened new options to further develop a potential cancer-fighting therapy, clearing an early hurdle in the lengthy drug-discovery process. The findings, published online on December 18, 2017 in the Journal of Biological Chemistry (JBC), reveal new ways to measure the activity of a protein that is associated with poor prognosis in cancer patients -- heat shock protein 70 (Hsp70) (image) -- and remove a barrier to developing potential Hsp70-based therapies. The article is titled “X-Linked Inhibitor of Apoptosis Protein (XIAP) is a Client of Heat Shock Protein 70 (Hsp70) and a Biomarker of Its Inhibition.” The significance of these findings led the study to be chosen as the JBC Editors' Pick for the upcoming February 16, 2018 issue. This honor is reserved for the top 2 percent of the more than 6,600 papers published in the journal each year, in terms of the overall importance of the research. When Hsp70 is present at increased levels, cancer cells are more likely to survive and become resistant to chemotherapeutics. Conversely, when this protein is inhibited in cells, tumor cells are less able to divide, and they eventually die. Because of its apparent role in cancer cell survival, researchers are interested in developing drugs that block the protein's activity. But these efforts have been hindered by a lack of Hsp70 biomarkers -- measurable surrogates that scientists can evaluate to ensure the compounds they are testing really do what they are supposed to do. Scientists have found some small molecules that affect Hsp70 in an artificial environment, where they can directly measure Hsp70 activity.

February 10th

Undergraduate Student Uncovers 22 Genes Associated with Glioblastoma; Findings Suggest Disease-Specific Regulatory Mechanism

When Leland Dunwoodie, an undergraduate researcher in biochemistry, approached his primary investigator about wanting to start research on "some human stuff" in the spring of 2016, he didn't imagine it would lead to the discovery of 22 genes that are implicated in glioblastoma, the most aggressive type of brain cancer. "I definitely didn't come to Clemson thinking about brain cancer research," Dunwoodie said. "I was working on a project with grapes and other plants. I told Dr. (Alex) Feltus that I wanted to do some human stuff, and he said, 'That's cool - pick an organ.' " After consulting with his family - should he study the brain or the heart? - Dunwoodie decided on the brain, and specifically on brain cancer. A prior summer internship at the Van Andel Institute in Michigan had spurred his interest in cancer research. Fast-forward two years later to an online January 13, 2018 publication in the journal Oncotarget, Dunwoodie's study is the first to describe glioblastoma-specific gene co-expression relationships among a group of 22 specific genes. The article is titled “Discovery and Validation of a Glioblastoma Co-Expressed Gene Module.” Heard of in the news as the disease afflicting Senator John McCain and Beau Biden, the late son of U.S. Vice President Joe Biden, glioblastoma is highly malignant and is characterized by its lethality. Patients with glioblastoma have a median survival time of only 14.6 months after diagnosis. "Like many other tumors, diseases, and complex traits, glioblastoma is controlled by a variety of genetic and epigenetic factors," Dunwoodie said. "If there was one master-regulator of these cancers, we'd say, 'We're going to drug that, and we're going to save millions of lives every year,' but there are more things going on in glioblastoma than we can presently identify."

February 9th

Stem Cell Research Provides Hope for Tasmanian Devils with Deadly, Transmissible Cancer

Morris Animal Foundation-funded researcher Dr. Deanne Whitworth, and her colleagues at the University of Queensland in Australia, have taken the first step toward developing an effective treatment for devil facial tumor disease (DFTD), which is decimating Tasmanian devils in the wild. The team's findings were published in the January 15, 2018 issue of Stem Cells and Development. The article is titled “Induced Pluripotent Stem Cells from a Marsupial, the Tasmanian Devil (Sarcophilus harrisii): Insight into the Evolution of Mammalian Pluripotency.” The University of Queensland team has been exploring the possibility of using stem-cell therapy to eradicate tumor cells from Tasmanian devils suffering from DFTD, a deadly transmissible cancer unique to this species. But first they had to find ways to grow and maintain marsupial stem cells, a feat that has not been achieved until now. Dr. Whitworth and her team successfully generated induced pluripotent Tasmanian devil stem cells in the laboratory. The team generated the cells as a first step toward developing a novel and effective treatment for devil facial tumor disease. "Since its discovery in 1996, DFTD has decimated 95 percent of the devil population," said Dr. Whitworth. "It is estimated that within 20 to 30 years, the devil will be extinct in the wild. Our work is moving us closer to finding a strategy to prevent the spread of DFTD and to cure animals already infected with the disease." Induced pluripotent stem cells are cells that have been reprogrammed back to an embryonic stem-cell-like state. The generation of these special cells from humans and other mammals has paved the way for the expanding field of stem cell research and new therapies.

Liver Cells with Whole Genome Duplications Protect Against Cancer in Mice

Researchers at the Children's Medical Center Research Institute (CRI) at the University of Texas (UT) Southwestern have discovered that cells in the liver with whole genome duplications, known as polyploid cells, can protect the liver against cancer. The study, published online on February 8, 2018 in Developmental Cell, addresses a long-standing mystery in liver biology and could stimulate new ideas to prevent cancer. The article is titled “The Polyploid State Plays a Tumor-Suppressive Role in the Liver.” Most human cells are diploid, carrying only one set of matched chromosomes that contain each person's genome. Polyploid cells carry two or more sets of chromosomes. Although rare in most human tissues, these cells are prevalent in the hearts, blood, and livers of mammals. Polyploidization also increases significantly when the liver is exposed to injury or stress from fatty liver disease or environmental toxins that could cause liver cancer later in life. It is unknown, however, whether these increases in polyploidization have functional importance. Previous research into the exact function of polyploid liver cells has been limited, in part because it has been difficult to change the number of sets of chromosomes in a cell, or ploidy, without introducing permanent mutations in genes that may also affect other cellular activities, such as division, regeneration, or cancer development. Because of this, there were many ideas as to why the liver is polyploid, but little experimental evidence. CRI researchers have discovered a new approach. "Our lab has developed new methods to transiently and reversibly alter ploidy for the first time. This was an important advance because it allowed us to separate the effects of ploidy from the effects of genes that change ploidy.

New Study Provides First 3D Visualization of Dynein-Dynactin Complex Bound to Microtubules

On the cellular highway, motor proteins called dyneins rule the road. Dyneins "walk" along structures called microtubules to deliver cellular cargo, such as signaling molecules and organelles, to different parts of a cell. Without dynein on the job, cells cannot divide and people can develop neurological diseases. Now, a new study, which was published on February 7, 2018 in Nature Structural & Molecular Biology, provides the first three-dimensional (3D) visualization of the dynein-dynactin complex bound to microtubules. The article is titled “Cryo-Electron Tomography Reveals That Dynactin Recruits a Team of Dyneins for Processive Motility.” The study leaders from The Scripps Research Institute (TSRI) report that a protein called dynactin hitches two dyneins together, like a yoke locking together a pair of draft horses. "If you want a team of horses to move in one direction, you need to line them up," says Gabriel C. Lander, PhD, a TSRI Associate Professor and senior author of the study. "That's exactly what dynactin is doing to dynein molecules." Understanding how the dynein-dynactin complex is assembled and organized provides a critical foundation to explain the underlying causes of several dynein-related neurodegenerative diseases such as spinal muscular atrophy (SMA) and Charcot-Marie-Tooth (CMT) disease. Researchers knew that dynactin is required for dynein to move cargo, but they struggled to get a complete picture of how the different parts of the complex worked together. "We knew that dynein only becomes active when it binds with a partner called dynactin. The problem was that, historically, it was difficult to solve this structure because it is very flexible and dynamic," explains Danielle Grotjahn, a TSRI graduate student and co-first author of the study.

Clock Protein Rev-erbα Represses Transcription by Loosening Chromosome Loops

It is well known that the human body functions on a 24-hour, or circadian, schedule. The up-and-down daily cycles of a long-studied clock protein called Rev-erb coordinates the ebb and flow of gene expression by tightening and loosening loops in chromosomes, according to new research from the Perelman School of Medicine at the University of Pennsylvania. The findings were published online on February 8, 2018 in Science. The article is titled “Rev-erbα Dynamically Modulates Chromatin Looping to Control Circadian Gene Transcription.” Over the last 15-plus years, a team led by the new study's senior author Mitchell A. Lazar, MD, PhD, Director of Penn's Institute for Diabetes, Obesity, and Metabolism, has been teasing out the versatile role of Rev-erb in maintaining daily cycles of the body's molecular clock, metabolism, and even brain health. "Many studies, including this one, point to a link between the human internal clock and such metabolic disorders as obesity and diabetes," Dr. Lazar said. "Proteins such as Rev-erb are the gears of the clock and understanding their role is important for investigating these and many other diseases." Human physiology works on a 24-hour cycle of gene expression (when the chromosome coding region is translated by RNA and then transcribed to make protein) and is controlled by the body's molecular clock. Core clock proteins activate or repress protein complexes that physically loop one part of a chromosome to become adjacent to a distant part of the same chromosome. The Penn team showed that daily oscillations of Rev-erb control gene expression in the mouse liver via interactions between on-and-off regions on the same chromosome.

Scientists Describe On-Off Switch for Inflammasomes; Finding May Advance Understanding of Inflammation in Many Diseases, Including Alzheimer’s

A discovery by Queensland scientists in Australia could be the key to stopping damage caused by uncontrolled inflammation in a range of common diseases including liver disease, Alzheimer's, and gout. University of Queensland (UQ) researchers have uncovered how an inflammation process automatically switches off in healthy cells, and are now investigating ways to stop it manually when it goes awry. UQ's Institute for Molecular Bioscience (IMB) researcher Associate Professor Kate Schroder (photo) said this inflammation pathway drove many different diseases. "Now that we understand how this pathway naturally turns off in health, we can investigate why it doesn't turn off in disease -- so it's very exciting," Dr. Schroder said. Her work at IMB's Centre for Inflammation and Disease Research focuses on inflammasomes, which are machine-like protein complexes at the heart of inflammation and disease. "These complexes form when an infection, injury, or other disturbance is detected by the immune system, and they send messages to immune cells to tell them to respond," Dr. Schroder said. "If the disturbance can't be cleared, such as in the case of amyloid plaques in Alzheimer's, these molecular machines continue to fire, resulting in neurodegenerative damage from the sustained inflammation." Dr. Schroder's team, led by Dr. Dave Boucher, discovered that inflammasomes normally work with an in-built timer switch, to ensure they only fire for a specific length of time once triggered. "The inflammasome initiates the inflammation process by activating a protein that functions like a pair of scissors, and cuts itself and other proteins," Dr. Schroder said.

February 8th

A Possible Mechanism by Which Viruses Can Establish Chronic Infections; Some Viruses Drive Production of Cytokine That Inhibits Function of CD8+ T-Cells

How do viruses that cause chronic infections, such as those caused by HIV or hepatitis c virus, manage to outsmart their hosts' immune systems? The answer to that question has long eluded scientists, but new research from McGill University has uncovered a molecular mechanism that may be a key piece of the puzzle. The discovery could provide new targets for treating a wide range of diseases. Fighting off infections depends largely on our bodies' capacity to quickly recognize infected cells and destroy them, a job carried out by a class of immune cells known as CD8+ T-cells. These soldiers get some of their orders from chemical mediators known as cytokines that make them more or less responsive to outside threats. In most cases, CD8+ T-cells quickly recognize and destroy infected cells to prevent the infection from spreading. "When it comes to viruses that lead to chronic infection, immune cells receive the wrong set of marching orders, which makes them less responsive," says Martin Richer, PhD, an Assistant Professor at McGill's Department of Microbiology & Immunology and senior author of the study, published online on January 23, 2018 Immunity. The article is titled “Interleukin-10 Directly Inhibits CD8+ T Cell Function by Enhancing N-Glycan Branching to Decrease Antigen Sensitivity.” The research, conducted in Dr. Richer's lab by graduate student Logan Smith, revealed that certain viruses persist by driving the production of a cytokine (IL-10, image shown here) that leads to modification of glycoproteins on the surface of the CD8+ T-cells, making the cells less functional. That maneuver buys time for the pathogen to outpace the immune response and establish a chronic infection. Importantly, this pathway can be targeted to restore some functionality to the T-cells and enhance the capacity to control infection.