Category Archives: Biochemistry

DUBLIN--(BUSINESS WIRE)--The "Role of Chitosan and Chitosan-Based Nanomaterials in Plant Sciences. Nanomaterial-Plant Interactions" book from Elsevier Science and Technology has been added to ResearchAndMarkets.com's offering.

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Key Topics Covered:

For more information about this book visit https://www.researchandmarkets.com/r/mbi2dq

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Role of Chitosan and Chitosan-Based Nanomaterials in Plant Sciences: Nanomaterial-Plant Interactions - The Physiological, Morphological, Biochemical...

New research provides fresh insight into how an important class of molecules are created and moved in human cells.

For years, scientists knew that mitochondria specialized structures inside cells in the body that are essential for respiration and energy production were involved in the assembly and movement of iron-sulfur cofactors, some of the most essential compounds in the human body. But until now, researchers didnt understand how exactly the process worked.

New research, published in the journal Nature Communications, found that these cofactors are moved with the help of a substance called glutathione, an antioxidant that helps prevent certain types of cell damage by transporting these essential iron cofactors across a membrane barrier.

Mechanism of cluster transport by Atm1.

Glutathione is especially useful as it aids in regulating metals like iron, which is used by red blood cells to make hemoglobin, a protein needed to help carry oxygen throughout the body, said James Cowan, co-author of the study and a distinguished university professor emeritus in chemistry and biochemistry at Ohio State.

Iron compounds are critical for the proper functioning of cellular biochemistry, and their assembly and transport is a complex process, Cowan said. We have determined how a specific class of iron cofactors is moved from one cellular compartment to another by use of complex molecular machinery, allowing them to be used in multiple steps of cellular chemistry.

Iron-sulfur clusters are an important class of compounds that carry out a variety of metabolic processes, like helping to transfer electrons in the production of energy and making key metabolites in the cell, as well as assisting in the replication of our genetic information.

But when these clusters don't work properly, or when key proteins cant get them, then bad things happen, Cowan said.

If unable to function, the corrupted protein can give rise to several diseases, including rare forms of anemia, Friedreichs ataxia (a disorder that causes progressive nervous system damage), and a multitude of other metabolic and neurological disorders.

So to study how this essential mechanism works, researchers began by taking a fungus called C. thermophilum, identifying the key protein molecule of interest, and producing large quantities of that protein for structural determination. The study notes that the protein they studied within C. thermophilum is essentially a cellular twin of the human protein ABCB7, which transfers iron-sulfur clusters in people, making it the perfect specimen to study iron-sulfur cluster export in people.

By using a combination of cryo-electron microscopy and computational modeling, the team was then able to create a series of structural models detailing the pathway that mitochondria use to export the iron cofactors to different locations inside the body. While their findings are vital to learning more about the basic building blocks of cellular biochemistry, Cowan said hes excited to see how their discovery could later advance medicine and therapeutics.

By understanding how these cofactors are assembled and moved in human cells, we can lay the groundwork for determining how to prevent or alleviate symptoms of certain diseases, he said. We can also use that fundamental knowledge as the foundation for other advances in understanding cellular chemistry.

This article was republished with permission from The Ohio State University. Read the original.

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How a complex molecule moves iron through the body - ASBMB Today

McMaster researchers have discovered a previously unknown bacteria-killing toxin that could pave the way for a new generation of antibiotics.

The study, led by John Whitney at the Michael G. DeGroote Institute for Infectious Disease Research, shows that the bacterial pathogen Pseudomonas aeruginosa, known to cause hospital-acquired infections such as pneumonia, secretes a toxin that has evolved to kill other species of bacteria.

Courtesy of Blake Dillon/McMaster University

John Whitney (right) and Nathan Bullen have studied this toxin for nearly three years.

For Whitney, the key aspect of his discovery is not just that this toxin kills bacteria, but how it does so.

This research is significant, because it shows that the toxin targets essential RNA molecules of other bacteria, effectively rendering them non-functional, says Whitney, an associate professor in the department of biochemistry and biomedical sciences.

Like humans, bacteria require properly functioning RNA in order to live.

First study author Nathan Bullen, a graduate student in biochemistry and biomedical sciences, describes it as a total assault on the cell because of the number of essential pathways depend on functional RNAs.

Whitney and Bullen, together with colleagues at Imperial College London and the University of Manitoba, have studied this toxin for nearly three years to understand exactly how it functions at a molecular level.

This is the graphical abstract for the team's paper, "An ADP-ribosyltransferase toxin kills bacterial cells by modifying structured non-coding RNAs."

The breakthrough, published in the journalMolecular Cell, was achieved by Bullen after rigorous experimentation on common targets of toxins, such as protein and DNA molecules, before eventually testing the toxin against RNA.

This discovery breaks well-established precedents set by protein-targeting toxins secreted by other bacteria, such as those that cause cholera and diphtheria.

Researchers say that this development holds great potential for future research that could eventually lead to new innovations that combat infection-causing bacteria.

Whitney says future antibiotic development can build on the newly discovered vulnerability.

This article was republished with permission from the Institute for Infectious Disease Research at McMaster University. Read the original.

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Researchers discover toxin that kills bacteria in unprecedented ways - ASBMB Today

The Decipher genomic classifier (GC) has demonstrated the ability to predict prostate cancer outcomes independently. Researchers sought to verify the GC in a randomized phase III trial of dose-escalated salvage radiotherapy (SRT) following radical prostatectomy.

In a phase III trial of 350 men with biochemical recurrence after radical prostatectomy who were randomly assigned to 64 Gy or 70 Gy without concurrent hormonal therapy or pelvic nodal RT, a clinical-grade whole-transcriptome assay was performed on radical prostatectomy samples obtained from patients enrolled in Swiss Group for Clinical Cancer Research (SAKK) 09/10. A predetermined statistical strategy was created to determine how the GC will affect clinical results. The main outcome was biochemical development; the secondary outcomes were clinical development and delay in hormone treatment. Age, T-category, Gleason score, post radical prostatectomy persistent prostate-specific antigen (PSA), PSA at randomization, and randomization arm were all adjusted in multivariable analyses to take competing hazards into account.

With a median follow-up of 6.3 years, the analytic cohort of 226 patients was typical of the whole experiment (interquartile range 6.1-7.2 years). The GC (high versus low-intermediate) was independently correlated with biochemical progress (subdistribution hazard ratio (sHR) 2.26, 95% CI1.42-3.60; P<0.001), clinical progress (HR 2.29, 95% CI 1.32-3.98; P=0.003), and hormone therapy use (sHR 2.99, 95% CI 1.55-5.76; P=0.001). Compared to GC low-intermediate patients, GC high patients had 5-year independence from biochemical advancement of 45% as opposed to 71%. Both the general cohort and individuals with lower vs. higher GC scores did not benefit from the dose increase.

The predictive value of the GC has been proven in this investigation, which is the first modern randomized controlled trial in patients treated with early SRT without concomitant hormone treatment or pelvic nodal RT. High-GC patients were more than twice as likely to develop biochemical and clinical progression and undergo salvage hormone treatment than lower-GC patients, independent of common clinicopathologic factors and RT dosage. These findings support the therapeutic utility of Decipher GC for individualized concurrent systemic treatment in the context of postoperative salvage.

Reference: annalsofoncology.org/article/S0923-7534(22)01205-4/fulltext

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Decipher GC Validation in Patients Receiving SRT Without Hormone Therapy after Radical Prostatectomy - Physician's Weekly

image:Pierre-Andre Jacinthe of Indiana University Purdue University Indianapolis (IUPUI) Selected as AAAS S&T Policy Fellow view more

Credit: IUPUI School of Science

The American Association for the Advancement of Science (AAAS) is pleased to announce the 50th class of the Science & Technology Policy Fellowships (STPF), who will help inform actionable, science-based policies throughout the U.S. government. Among the 300 highly trained scientists and engineers selected, Dr. Pierre-Andre Jacinthe, a professor of soil biogeochemistry in the Department of Earth Sciences at IUPUI, will spend a year serving at the U.S. Agency for International Development (USAID) in the Bureau for Resilience and Food Security (BFS). The Bureau leads the implementation of Feed the Future, the U.S. Governments program to sustainably reduce global hunger, malnutrition and poverty through agriculture-led economic growth.

Climate change poses a real challenge to food production systems, and more so in the resource-poor regions of the world, Jacinthe said. Feed the Future has a special focus on these vulnerable communities and strives for the emergence of sustainable production systems that are resilient to climate-related stresses. I am both excited and honored to have the opportunity to contribute to the BFS mission.

Fellows like Dr. Jacinthe will learn first-hand about federal policymaking and implementation, while the U.S. government benefits from the contributions of highly trained scientists and engineers.

AAAS policy fellows have been demonstrating excellence in science policy for the past half-century defining what it means to be a scientist and engineer in the policymaking realm, said Rashada Alexander, Ph.D., STPF director and alumna fellow. In our 50th year of partnership with the U.S. government and many esteemed scientific societies and supporters, we are excited to usher in the newest class and follow their important contributions to policy, science and society.

The STPF program supports evidence-based policymaking by leveraging the knowledge and analytical mindset of science and engineering experts, and trains leaders for a strong U.S. science and technology enterprise. Fellows represent a full spectrum disciplines, backgrounds and career stages.

We are incredibly proud of Dr. Jacinthe and his remarkable accomplishment of being selected as an AAAS Science & Technology Policy Fellow, said John DiTusa, dean of the IUPUI School of Science. This is a wonderful recognition of the quality of his previous work in the field of biogeochemistry of soils as a faculty member of the School of Science. I know Dr. Jacinthes important work with the BFS on the impact of climate change on soil biochemistry and on food production will lead to crucial scientific contributions for policy development worldwide and inform future exploration.

The 2022-23 fellowship class is sponsored by AAAS, the Moore Foundation and partner societies. Of the 300 fellows chosen, 31 will serve in Congress, one will serve at the Federal Judicial Center, and 268 will serve in the executive branch among 19 federal agencies or departments.

After the fellowship, many remain in the policy arena working at the federal, state, regional or international level, while others pursue careers in academia, industry or the nonprofit sector.

Founded in 1973, the STPF program will turn 50 in 2023. AAAS will celebrate this milestone as STPF establishes a formal alumni network about 4,000 strong to stimulate and support collaboration among alumni fellows to further the STPF mission to connect evidence-based decision-making with public policy.

Visit http://www.aaas.org/stpf to learn more about the AAAS S&T Policy Fellowships.

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

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Pierre-Andre Jacinthe of Indiana University Purdue University Indianapolis (IUPUI) selected as AAAS S&T Policy Fellow - EurekAlert

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Atavistik Bio, a pre-clinical biotechnology company that is leveraging their scalable and systematic platform to identify novel regulatory sites on proteins to restore function in disease, announced the formation of its Scientific Advisory Board (SAB) comprised of distinguished leaders in protein sciences, inborn errors of metabolism, and cancer.

We are proud and honored to have these accomplished scientific leaders join our Scientific Advisory Board, said Marion Dorsch, President and CSO of Atavistik Bio. Together, they bring a wealth of knowledge and experience for Atavistik Bio as we leverage our powerful screening and analytics platforms to unlock the potential of protein-metabolite interactions with the goal to bring transformative therapies to patients. Atavistik Bio looks forward to the input of these outstanding scientists and their contribution to our research and development efforts. Feedback and collaboration with our SAB will be critical to advance our efforts to develop therapies to patients in need. It is a very exciting time for all of us at Atavistik Bio.

The founding members of the Atavistik Bio Scientific Advisory Board are:

Dr. Ralph DeBerardinis is Chief of Pediatric Genetics and Metabolism at UT Southwestern Medical Center (UTSW) and Director of the Genetic and Metabolic Disease Program at Childrens Medical Center Research Institute at UTSW (CRI). His laboratory studies the role of altered metabolic pathways in human diseases, including cancer and pediatric inborn errors of metabolism. Work from the DeBerardinis laboratory has produced new insights into disease mechanisms in numerous metabolic diseases, including by defining unexpected fuel preferences in human cancer and uncovering new metabolic vulnerabilities in cancer cells. Dr. DeBerardinis is a Howard Hughes Medical Institute Investigator and has received numerous awards including the William K. Bowes, Jr. Award in Medical Genetics, the National Cancer Institutes Outstanding Investigator Award, The Academy of Medicine, Engineering & Science of Texass Edith and Peter ODonnell Award in Medicine, and the Paul Marks Prize for Cancer Research from Memorial Sloan Kettering Cancer Center. He has been elected to the National Academy of Medicine and the Association of American Physicians.

Dr. DeBerardinis received a BS in Biology from St. Josephs University in Philadelphia before earning MD and PhD degrees from the University of Pennsylvanias School of Medicine. He completed his medical residency and post-doctoral training at The Childrens Hospital of Philadelphia (CHOP) in Pediatrics, Medical Genetics and Clinical Biochemical Genetics.

Dr. Jared Rutter is a Distinguished Professor of Biochemistry and holds the Dee Glen and Ida Smith Endowed Chair for Cancer Research at the University of Utah where he has been on the faculty since 2003. His laboratory has identified the functions of several previously uncharacterized mitochondrial proteins, including the discovery of the long-sought mitochondrial pyruvate carrier. This knowledge has demonstrated that this critical metabolic step is impaired in a variety of human diseases, including cancer and cardiovascular disease. In addition, the Rutter lab is taking multiple approaches to understand how metabolic state influences cell fate and cell behavior decisions. Dr. Rutter has been an Investigator of the Howard Hughes Medical Institute since 2015 and serves as co-Director of the Diabetes and Metabolism Center at the University of Utah and co-Leader of the Nuclear Control of Cell Growth and Differentiation at Huntsman Cancer Institute.

Dr. Rutter performed undergraduate studies at Brigham Young University and received his PhD from the University of Texas Southwestern Medical Center in 2001, working with Dr. Steve McKnight. After receiving his PhD, he spent 18 months as the Sara and Frank McKnight Independent Fellow of Biochemistry before joining the faculty at the University of Utah.

Karen Allen, Ph.D. is Professor and Chair of Chemistry at Boston University. For over 25 years, she has led research teams at Boston University, in the Departments of Physiology and Biophysics at the School of Medicine, and Chemistry. She is also a Professor of Material Science and Engineering and on the faculty of the Bioinformatics program at Boston University. The structure-aided design approach in the Allen lab encompasses the use of macromolecular X-ray crystallography, small-angle X-ray scattering, molecular modeling, and kinetics.

Karen received her B.S. degree in Biology, from Tufts University and her Ph.D. in Biochemistry from Brandeis University in the laboratory of the mechanistic enzymologist, Dr. Robert H. Abeles. Following her desire to see enzymes in action she pursued X-ray crystallography during postdoctoral studies as an American Cancer Society Fellow in the laboratory of Drs. Gregory A. Petsko and Dagmar Ringe.

Kivanc Birsoy, Ph.D. is a Chapman-Perelman Associate Professor at Rockefeller University. His research at Rockefeller focuses on how cancer cells rewire their metabolic pathways to adapt to environmental stresses during tumorigenesis and other pathological states. He is the recipient of numerous awards, including the Leukemia and Lymphoma Society Special Fellow award, Margaret and Herman Sokol Award, NIH Career Transition Award, Irma Hirschl/Monique Weill-Caulier Trusts Award, Sidney Kimmel Cancer Foundation Scholar Award, March of Dimes Basil OConnor Scholar Award, AACR NextGen award for Transformative Cancer Research, Searle Scholar, Pew-Stewart Scholarship for Cancer Research and NIH Directors New Innovator Award.

Kivanc received his undergraduate degree in Molecular Genetics from Bilkent University in Turkey in 2004 and his Ph.D. from the Rockefeller University in 2009, where he studied the molecular genetics of obesity in the laboratory of Jeffrey Friedman. In 2010, he joined the laboratory of David Sabatini at the Whitehead Institute of Massachusetts Institute of Technology (MIT) where he combined forward genetics and metabolomics approaches to understand how different cancer types rewire their metabolism to adapt nutrient deprived environments.

Benjamin Cravatt, Ph.D. is the Gilula Chair of Chemical Biology and Professor in the Department of Chemistry at The Scripps Research Institute. His research group develops and applies chemical proteomic technologies for protein and drug discovery on a global scale and has particular interest in studying biochemical pathways in cancer and the nervous system. His honors include a Searle Scholar Award, the Eli Lilly Award in Biological Chemistry, a Cope Scholar Award, the ASBMB Merck Award, the Wolf Prize in Chemistry, and memberships in the National Academy of Sciences, National Academy of Medicine, and American Academy of Arts and Sciences. Ben is a co-founder of several biotechnology companies, including Activx Biosciences (acquired by Kyorin Pharmaceuticals), Abide Therapeutics (acquired by Lundbeck Pharmaceuticals), Vividion Therapeutics (Acquired by Bayer Pharmaceuticals), Boundless Bio, Kisbee Therapeutics, and Kojin Therapeutics.

Ben obtained his undergraduate education at Stanford University, receiving a B.S. in the Biological Sciences and a B.A. in History. He then received a Ph.D. from The Scripps Research Institute (TSRI) in 1996, and joined the faculty at TSRI in 1997.

The SAB will be co-chaired by Dr. DeBerardinis and Dr. Rutter, the scientific founders of Atavistik Bio, and work closely with the company to advance their leading-edge metabolite protein screening platform discovery programs. Im delighted to be appointed Co-Chair of Atavistik Bios Scientific Advisory Board, and to be part of such a distinguished group of experts, said Dr. DeBerardinis. Together we aim to guide Atavistik Bio through the development of its pipeline while maximizing the potential of the companys technology platform, stated Dr. Rutter.

About Atavistik Bio

Atavistik Bio is a pre-clinical biotechnology company that is harnessing the power of protein-metabolite interactions to add a new lens to drug discovery with the aim of transforming the lives of patients. By leveraging its optimized Atavistik Metabolite Protein Screening (AMPS) platform and computational approaches, Atavistik Bio aims to evaluate metabolite-protein interactions by screening proteins with their proprietary metabolite library to determine where binding sites with biological relevance might exist. This will enable Atavistik Bio to build an extensive protein-metabolite database map (the Interactome) to reveal unique insights into the crosstalk between metabolite-protein pathways that were previously thought to be unrelated. Utilizing advanced informatics tools, deep expertise in chemistry and computationally rich structure-based drug design, Atavistik Bio will be able to identify and understand the role of these interactions across important biological and disease-relevant pathways to drive the discovery of novel therapeutics with an initial focus on inborn errors of metabolism and cancer. Atavistik Bio is located in Cambridge, Massachusetts. For more information, visit http://www.atavistikbio.com.

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Atavistik Bio Announces Formation of Scientific Advisory Board - Business Wire