Syndicate content

Archive - Feb 2018

Date

February 17th

Dynamic Ligand Discrimination Shown in Notch Signaling Pathway

Multicellular organisms like ourselves depend on a constant flow of information between cells, coordinating their activities in order to proliferate and differentiate. Deciphering the language of intercellular communication has long been a central challenge in biology. Now, Caltech scientists have discovered that cells have evolved a way to transmit more messages through a single pathway, or communication channel, than previously thought, by encoding the messages rhythmically over time. The work, conducted in the laboratory of Michael Elowitz (photo), PhD, Professor of Biology and Bioengineering, Howard Hughes Medical Institute Investigator, and Executive Officer for Biological Engineering, is described in a paper in the February 8, 2018 issue of Cell. The open-access paper is titled "Dynamic Ligand Discrimination in the Notch Signaling Pathway." In particular, the scientists studied a key communication system called "Notch," which is used in nearly every tissue in animals. Malfunctions in the Notch pathway contribute to a variety of cancers and developmental diseases, making it a desirable target to study for drug development. Cells carry out their conversations using specialized communication molecules called ligands, which interact with corresponding molecular antennae called receptors. When a cell uses the Notch pathway to communicate instructions to its neighbors--telling them to divide, for example, or to differentiate into a different kind of cell--the cell sending the message will produce certain Notch ligands on its surface. These ligands then bind to Notch receptors embedded in the surface of nearby cells, triggering the receptors to release gene-modifying molecules called transcription factors into the interior of their cell.

February 13th

ASHG Disappointed by Proposed NIH Budget for FY 2019

On February 13, 2018, The American Society of Human Genetics (ASHG) announced that it is disappointed by the Administration’s proposed Fiscal Year 2019 National Institutes of Health (NIH) budget released on February 12, 2018. This budget would impose cuts to the budgets of most NIH institutes and centers, including those institutes supporting most genetics research. “NIH funding is the lifeblood of genetics research in the United States,” said ASHG President David L. Nelson, PhD. “It connects our nation to global collaborations that are advancing science and improving health. Because of crucial federal support for such research, we are making remarkable progress in understanding how the human genome operates and how this knowledge can enhance patient care. Yet there are still fundamental questions that researchers are working to answer, which will pave the way for better health for future generations,” he added. “Whether for pioneering projects like the All of Us Research Program or for innovative investigator-initiated research, this investment is essential for discovering breakthrough diagnostics and treatments. We are heartened that there is broad bipartisan consensus in Congress to increase federal funding for biomedical research, and we thank and look forward to working with Congressional leaders to support sustained investment.”

[Press release]

Huntington’s Disease Provides Potentially Powerful New Cancer Weapon; Small Interfering RNAs (siRNAs) Based on Huntingtin Trinucleotide Repeats (TNRs) Are Highly Toxic to Cancer Cells

Patients with Huntington’s disease, a fatal genetic illness that causes the breakdown of nerve cells in the brain, have up to 80 percent less cancer than the general population. Northwestern Medicine scientists have discovered why Huntington’s is so toxic to cancer cells and have harnessed some of the disease’s characteristics for a novel approach to treat cancer, according to a new study published online on February 12, 2018 in EMBO Reports. The article is titled “Small Interfering RNAs Based on Huntingtin Trinucleotide Repeats Are Highly Toxic to Cancer Cells.” Huntington’s is caused by a prominent trinucleotide repeat (TNR) expansion in the numbers of the CAG triplets in the huntingtin (HTT) gene responsible, when mutated, for Huntington's disease (HD). Pathology is caused by protein and RNA generated from the TNR regions, including small interfering RNA (siRNA)‐sized repeat fragments. The HTT gene is present in every cell and the defect that causes the disease is also highly toxic to tumor cells. These siRNAs from the mutated huntingtin gene attack genes in the cell that are critical for survival. Nerve cells in the brain are vulnerable to this form of cell death, however, cancer cells appear to be much more susceptible. “This molecule is a super assassin against all tumor cells,” said senior author Marcus Peter, PhD, the Tom D. Spies Professor of Cancer Metabolism and of Medicine in the Division of Hematology and Oncology. “We’ve never seen anything this powerful against cancer cells.” The researchers showed that siRNAs based on the CAG TNR are toxic to cancer cells by targeting genes that contain long reverse complementary TNRs in their open reading frames. Of the 60 siRNAs based on the different TNRs, the six members in the CAG/CUG family of related TNRs are the most toxic to both human and mouse cancer cells.

February 12th

Machine-Learning Algorithm Uses Time-Series Data to Reveal Underlying Gene Regulatory Networks in Cells

Biologists have long understood the various parts within the cell. But how these parts interact with and respond to each other is largely unknown. "We want to understand how cells make decisions, so we can control the decisions they make," said Northwestern University's Neda Bagheri (photo), PhD. "A cell might decide to divide uncontrollably, which is the case with cancer. If we understand how cells make that decision, then we can design strategies to intervene." To better understand the mysterious interactions that occur inside cells, Dr. Bagheri and her team have designed a new machine learning algorithm that can help connect the dots among the genes' interactions inside cellular networks. Called "Sliding Window Inference for Network Generation," or SWING, the algorithm uses time-series data to reveal the underlying structure of cellular networks. Supported by the National Science Foundation, the National Institutes of Health, and Northwestern's Biotechnology Training Program, the research was published online on February 12, 2018 in PNAS. Justin Finkle and Jia Wu, graduate students in Dr. Bagheri's laboratory, served as co-first authors of the paper, which is titled “Windowed Granger Causal Inference Strategy Improves Discovery of Gene Regulatory Networks.” In biological experiments, researchers often perturb a subject by altering its function and then measure the subject's response. For example, researchers might apply a drug that targets a gene's expression level and then observe how the gene and downstream components react. But it is difficult for those researchers to know whether the change in genetic landscape was a direct effect of the drug or the effect of other activities taking place inside the cell.

National Alliance for Hispanic Health Brings NIH's All of Us Journey to Oregon State University Feb 15

Oregon State University and the National Alliance for Hispanic Health will host the National Institutes of Health's All of Us Journey (https://www.joinallofus.org/journey) on Thursday, February 15, 2018. The traveling, hands-on exhibit raises awareness about the All of Us Research Program (https://allofus.nih.gov/)—an ambitious effort to gather data from 1 million or more people living in the United States to accelerate precision medicine research and improve health. "We are glad the National Alliance for Hispanic Health recognizes our region as an important stop on the national tour and they are taking on a national effort to focus on the Hispanic population. If you look at most biomedical, behavioral, or social science research, it doesn't involve the Hispanic population," said Javier Nieto, Dean of the College of Public Health and Human Sciences at Oregon State. "Most clinical trials and large population health studies do not include Hispanic participants. It is our duty to figure out how we can better their lives through science." Campus and community members are invited to come learn about the NIH’s All of Us program and get information on healthy living and preventing disease. Corvallis is one stop on the All of Us Journey's 37-week national tour. "All of Us is so important to shaping the future of health in the United States," said Dr. Jane L. Delgado, President and CEO of the National Alliance for Hispanic Health, the nation's leading Hispanic health advocacy group.

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 (https://www.drivendata.org/) 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.