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Archive - 2018

November 13th

2018 Lasker-Koshland Special Achievement Award in Medical Science Goes to Yale’s Pioneering Woman Biochemist Joan Steitz for Leadership in RNA Biology & Scientific Mentorship, Especially for Women

The 2018 Lasker-Koshland Award for Special Achievement in Medical Science honors an individual whose lifetime contributions have engendered among her colleagues the deepest feelings of awe and respect. For four decades, Joan Argetsinger Steitz (Yale University) has provided leadership in biomedical science. She has made pioneering discoveries about RNA biology, generously mentored budding scientists, and vigorously and passionately supported women in science. She has generated a cascade of discoveries that have illuminated wide-ranging and unanticipated functions for RNA molecules within our cells, and has served as a role model in multiple ways, especially for rising female investigators. Dr. Steitz has campaigned for full inclusion of all members of the scientific community, fueled by the conviction that reaching this goal is necessary to ensure a robust and innovative scientific enterprise. When Steitz encountered the molecular basis of genetics in the early 1960s as an undergraduate lab technician, she was enchanted, but despite her passion and curiosity, she could not envision a future for herself as an academic researcher. The absence of female biology professors shrouded that potential career path. She did know that women could be physicians, so she decided to become a doctor. The summer before medical school, Steitz joined the lab of Joseph Gall (Albert Lasker Special Achievement Award in Medical Science, 2006), where she undertook her first independent project. Thrilled by the joy of discovery and the challenges of steering her own experiments, she could no longer resist the draw of research.

November 13th

2018 Lasker-Debakey Clinical Medical Research Award Given to John Glen for Scottish Veterinarian’s Discovery & Development of Propofol, a Widely Used Anesthetic

The 2018 Lasker-DeBakey Clinical Medical Research Award honors John B. (Iain) Glen (retired from AstraZeneca), a Scottish veterinarian who discovered and developed propofol, a chemical whose rapid action and freedom from residual effects have made it the most widely used agent for induction of anesthesia in patients throughout the world. In 2016, the World Health Organization (WHO) deemed propofol an “essential medicine” and at the time of that decision, more than 190 million people had received the drug. In 1972, Dr. Glen joined Imperial Chemistry Industries (ICI; through mergers, ICI eventually became AstraZeneca) to help find new short-acting intravenous anesthetics. Eventually he took charge of the enterprise. The type of drug he sought—an induction agent—is used to sedate people so they can then tolerate inhaled anesthetics that maintain unconsciousness for long procedures. Administration of these gases through a mask can cause discomfort, and some of them can provoke an initial feeling of suffocation. The gold standard induction agent at the time was called thiopentone, which induced anesthesia quickly, but had limitations. Most prominent among them is that it builds up in the body, so repeated use during surgery would cause patients to remain unconscious long afterward. Dr. Glen’s team wanted to find a medication that possesses the anesthetic power of thiopentone, but allows rapid recovery. In addition to serving as a new induction agent, such a drug might maintain sedation and thus provide an injected alternative to inhaled anesthetics. The group also aimed to reduce common unpleasant after-effects of anesthesia such as nausea and vomiting.

European Society for Medical Oncology Will Give 2018 Immuno-Oncology Award to Cornelis Melief for Development of New Therapeutic Cancer Vaccine Strategies

The European Society for Medical Oncology (ESMO) (http://www.esmo.org) has selected Professor Cornelis Melief to receive the 2018 ESMO Immuno-Oncology Award (http://www.esmo.org/Career-Development/Awards/ESMO-Award-for-Immuno-Onco...) in recognition of his life's work in studying the interactions of the immune system with cancer. The distinction will be officially presented to him at the opening keynote and award lecture of this year's ESMO Immuno-Oncology Congress in Geneva, Switzerland (13-16 December) (http://www.esmo.org/Conferences/ESMO-Immuno-Oncology-Congress-2018). Professors George Coukos and John Haanen, Scientific Co-Chairs of the upcoming Congress (http://www.esmo.org/Conferences/ESMO-Immuno-Oncology-Congress-2018/Congr...), commented on the reasons for this nomination: "Professor Melief dedicated his career to understanding how the immune system, specifically cytotoxic lymphocytes, interact with cancer, and used this knowledge for the development of new therapeutic cancer vaccine strategies," said Professor Coukos. After studying virally induced cancer in mice, he is currently involved in clinical trials with synthetic vaccines for the treatment of head and neck, as well as cervical cancer, associated with the human papilloma virus (HPV). "With this award we are recognizing him as a true pioneer in the field of cancer immunology, who has trained and inspired a whole generation of young scientists with his research," Professor Haanen added.

DNA Script Announces World's First Enzymatic Synthesis of a High-Purity 150-Nucleotide Strand of DNA; Results Outpace Historical Trend for Phosphoramidite Chemistry

On October 2, 2018, DNA Script, which describes itself as "the global leader in the development of enzymatic DNA synthesis," announced that it has successfully synthesized the world's first 150-nucleotide (nt) strand of DNA by de novo enzymatic synthesis. DNA Script's enzymatic approach reaches up to 99.5 percent efficacy for each nucleotide added, achieving parity with traditional chemical synthesis. DNA Script shared these results during a presentation at SynBioBeta 2018 (https://2018.synbiobeta.com/) — the premier conference for synthetic biology, held in San Francisco. "The technology developed by DNA Script is now on par with the performance of current commercial solutions done with the aid of phosphoramidite reagents. DNA Script is the first organization — commercial or academic — to demonstrate the feasibility of enzymatic DNA synthesis, proving the incredible potential of this nascent technology. In May, we announced a world-first with the enzymatic synthesis of a 50-nt strand of DNA, and we have been able to triple our performance in just four months. By 2019, we expect to be able to synthesize DNA strands several hundred nucleotides in length. The speed at which our enzymatic synthesis technique has progressed — from a single incorporation to 150 nt in just four years — significantly outperforms the historical trend for phosphoramidite chemistry." said Thomas Ybert, PhD, CEO, and Co-Founder of DNA Script. In the experiments routinely run by the R&D team at DNA Script, sequences of the four natural nucleotides are randomly generated in silico and then automatically synthesized in vitro on the hardware platform developed by the company, without any physical template. Dr. Ybert added: "This is only the beginning. Our goal is now to go way beyond chemistry.

DNA Script, Enzymatic DNA Synthesis Company, Creates US Subsidiary & Expands Executive Team in US

On November 8, 2018, DNA Script, which describes itself as "the global leader in the development of enzymatic DNA synthesis," announced the creation of DNA Script Inc., its US subsidiary. The company also announced the expansion of its executive team in the US. Dr. Jeffrey Jeddeloh was appointed VP of Business Development and Commercial Strategy to facilitate partnering and strategy implementation. Dr. Stephen Macevicz was named VP of Intellectual Property. The appointment of Dr. Christine Peponnet as VP of Technology Development will strengthen the company's growing research and development organization. "Last month, we announced a major technology milestone for the nascent field of enzymatic DNA synthesis: the world's first synthesis of a 150-nucleotide (nt) strand of DNA using enzymes with up to 99.5 percent efficacy for each nucleotide added — achieving parity with traditional chemical synthesis," said Thomas Ybert, PhD, CEO, and Co-Founder of DNA Script. "In the last year, the company has increased secured financing to $27 million, was granted two patents, filed five new patent applications, and grew its team to 35. This is only a beginning, as we intend to release the first commercial products to early adopters within 12 months. Given the importance of the US market for DNA Script, crossing the ocean and structuring our executive team with industry veterans is absolutely key." Dr. Jeddeloh, 49, joins DNA Script as VP of Business Development and Commercial Strategy, bringing more than 20 years of experience commercializing technology and business leadership in the genomics and molecular biology tools space. He joined Roche after the NimbleGen Systems acquisition in 2007.

2018 Lasker Award for Basic Medical Research Goes to Grunstein & Allis for Discovering How Gene Expression Is Influenced by Histone Modification

The 2018 Albert Lasker Basic Medical Research Award honors two scientists for discoveries that have elucidated how gene expression is influenced by chemical modification of histones, the proteins that package DNA within chromosomes. This prestigious award, often a prelude to the NobelPrize, was announced on September 11, 2018. Through tour-de-force genetic studies in yeast, Michael Grunstein (University of California, Los Angeles) demonstrated that histones dramatically influence gene activity within living cells and laid the groundwork for understanding the pivotal role of particular amino acids in this process. C. David Allis (Rockefeller University) uncovered an enzyme that attaches a specific chemical group to a particular amino acid in histones, and this histone-modifying enzyme turned out to be an established gene co-activator whose biochemical capabilities had eluded researchers. Grunstein and Allis unveiled a previously hidden layer of gene control and broke open a new field. In the late 1800s, Albrecht Kossel discovered proteins called histones in goose blood cells. These abundant proteins, he showed, associate with nucleic acid to form a conglomerate called chromatin. Until the 1940s, many scientists thought that histones, not DNA, constituted the inherited material in eukaryotes, organisms whose cells contain nuclei. By the 1960s, however, DNA had stolen the genetic-code limelight. Still, histones were plentiful and their partnership with the all-important genes intrigued investigators. Perhaps, evidence suggested, the proteins stifle the production of RNA from DNA, a process called transcription. In this view, stripping histones from eukaryotic DNA would allow the molecular apparatus that synthesizes RNA to adhere to its template and do its job.

November 12th

Carnegie Mellon Scientists Overcome Major Obstacles to Realizing Enormous Potential of PNAs; Synthetic Molecules Can Invade Double-Stranded DNA or RNA Under Physiological Conditions; Potentially Powerful Gene Editing/Therapy Tools

Carnegie Mellon University researchers have developed a synthetic molecule that can recognize and bind to double-stranded DNA or RNA under normal physiological conditions. The molecule could provide a new platform for developing methods for the diagnosis and treatment of genetic conditions. Their findings were published online on November 7, 2018 in Communications Chemistry, a new Nature journal. The open-access article is titled “Shape Selective Bifacial Recognition of Double Helical DNA.” The work was carried out by an international team of experts, including Carnegie Mellon Professor of Chemistry Danith Ly, PhD, an expert in peptide nucleic acid (PNA) design; Chemistry postdoc Shivaji Thadke, PhD; and Chemistry graduate student Dinithi Perera; Chemistry Professor and Director of Carnegie Mellon’s nuclear magnetic resonance (NMR) Facility Roberto Gil, PhD, and Arnab Mukherjee, PhD, a computer scientist at The Indian Institute of Science Education and Research at Pune. "Since the double-helical structure of DNA was first elucidated by Watson and Crick, scientists have been trying to design molecules that can bind to DNA and allow one to control the flow of genetic information," said Dr. Ly. "This is the first bifacial molecule that can invade double-stranded DNA or RNA under biologically relevant conditions." DNA, which contains all of an organism's genetic information, is made up of two strands of nucleotides. The nucleotides connect with each other using hydrogen bonds, forming a helical chain of Watson-Crick base pairs. While these base pairs provide a relatively simple code to our genetic information, getting into the double helix to change the code is difficult due to the strong bonds between the base-pairs.

Codiak BioSciences Presents First Data on exoSTING—Company’s Proprietary Engineered Exosome, Incorporating a STING Agonist, Generated Potent, Targeted, and Sustained Antitumor Immunity

On November 6, 2018, Codiak BioSciences, Inc., a leading exosome therapeutics company, announced results from preclinical studies demonstrating the potential of Codiak's proprietary engineered exosome therapeutic, exoSTING. exoSTING is composed of precision engineered exosomes loaded with a potent small molecule STING (stimulator of interferon genes) agonist. The precision engineering of exoSTING provides for selective, preferential STING delivery to antigen presenting cells (APCs). In these preclinical studies, exoSTING generated potent, targeted, and sustained antitumor immunity - including in metastatic tumors - without systemic elevation of toxic cytokines. These data were presented on Saturday, November 10th at the 33rd Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (https://www.sitcancer.org/events/event-description?CalendarEventKey=a48f...) in Washington, DC, in a poster entitled, "Selective Delivery of Exosome-Mediated STING Agonist to Antigen Presenting Cells Results in Significantly Improved Potency and Reduced Toxicity" (#P618 ). "These studies highlight the unique profile of exoSTING to selectively activate the STING pathway in tumor-resident APCs, without toxic systemic cytokine elevation," said Douglas Williams, PhD, President and CEO of Codiak. "The potent T cell-mediated antitumor immune responses elicited with very low doses of STING agonists are the result of the rational drug design of exoSTING created using our proprietary exosome engineering platform, engEX™. In contrast with free STING agonists, exoSTING is highly potent, is not compromised by systemic cytokine production, and preserves the viability of T cells and antigen presenting cells, thereby markedly improving the therapeutic window.

Researchers Find New Pathway to Regulate Immune Response, Control Diseases; They Show That lncRNA HOTAIR Regulates LPS-Induced Cytokine Expression & Inflammatory Response in Macrophages

Researchers at The University of Texas at Arlington (UTA) have found a potential new pathway to regulate immune response and potentially control inflammatory diseases of the central nervous system such as meningitis and sepsis. "We need to know what turns on inflammatory response to bacterial infection to be able to modulate the process," said Subhrangsu Mandal, PhD, the UTA Associate Professor of Chemistry who led the research. "If we can do so, we can control inflammatory diseases of the central nervous system that have been hard to treat up to now, such as sepsis and meningitis, as well as cancer and muscular dystrophy, which can also be seen a kind of inflammation," he added. The research findings of Dr. Mandal’s team were published online on October 23, 2018 in Scientific Reports. The open-access article is titled “LncRNA HOTAIR Regulates Lipopolysaccharide-Induced Cytokine Expression and Inflammatory Response in Macrophages.” The researchers have found that the long non-coding RNA (lncRNA) molecule HOTAIR present in white blood cells has the capacity to signal these cells to activate immune response in the presence of bacteria. RNA is present in all living cells. Its primary role is to carry instructions from DNA. "Knowing that HOTAIR has a role in the signaling pathway also means that we can use it as a biomarker for bacterial infection," Dr. Mandal added.

November 11th

POTION Project Will Study Scent of Emotion; Planned Five-Year Project Has 6.5 Million Euros in Funding

What does fear smell like? And happiness? When we feel emotions do we emit substances specific to that particular emotional state which can be “smelled” by our peers? This is certainly true of animals, but for human beings, it has yet to be proven. Enzo Pasquale Scilingo, PhD, Professor of Electronic and Information Bioinformation at the Department of Information Engineering (DII) of the University of Pisa, who heads the Computational Physiology group at the Research Center “E. Piaggio,” is coordinating a project the aim of which is to study whether the emotions we feel lead us to emit specific molecules, identifiable through the sense of smell, by analyzing sweat. The project called POTION has been awarded over 6,500,000 euros, for a period of five years during which time Professor Scilingo will coordinate a consortium of 10 international partners from 8 different countries, each with a scientific profile which is complementary, multidisciplinary and of consolidated experience in the research sector referred to in the themes of the project. A team from the Department of Chemistry and Industrial Chemistry of the University of Pisa, coordinated by Professor Fabio di Francesco, will also be taking part in the project. Their task will be to identify and synthesize the molecules in question, using the most advanced analytical techniques. “POTION aims to study the human capacity to transmit emotions and influence social behaviour through body odor: chemosignals,” explains Professor Scilingo. “When we feel emotions such as happiness and fear, the human body produces chemosignals that are released through sweat and which could be emotionally contagious the moment they are perceived by others.