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

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

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.

Role of Chitosan and Chitosan-Based Nanomaterials in Plant Sciences explores the physiological, morphological, biochemical and molecular regulation of chitosan and chitosan-based nanoparticles in plants in normal conditions, as well as during different stresses, and their probable mechanism of operation in the tolerance mechanism.

The book stimulates further research in the field of chitosan and will foster further interests for researchers, academicians and scientists worldwide. Nanotechnology is being used widely in all disciplines of science and technology, including plant sciences.

Chitosan has widely been reported as a beneficial organic compound for the growth and developments of plants and it plays a protective role for the plants against abiotic and biotic stresses. Yet there are very few books available that deal exclusively with Chitosan and Chitosan based nanoparticles impacts on plants respectively.

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...

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

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

JERUSALEM, Sept. 19, 2022 /PRNewswire/ -- The Hadassah Cancer Research Institute (HCRI) at the Hadassah University Medical Center in Jerusalem, announced today that it is leading CancerRNA (www.cancerna.info), a global consortium that aims to apply RNA-based therapeutics to successfully unlock anti-cancer immune responses. While RNA-based therapies, namely mRNA vaccines, shined during the pandemic and saved millions of lives, they have yet to be successfully tested in cancer therapies. The HCRI hosted the opening meeting and workshops of CancerRNA in Jerusalem this month to plan, collaborate and advance the aims of this groundbreaking international consortium to impact the future of cancer treatment.

The CanceRNA team, led by Professor Michal Lotem, MD, Head of HCRI, the Center for Melanoma and Cancer Immunotherapy, and Prof. Rotem Karni Department Chair at Biochemistry and Molecular Biology, Hebrew University-Hadassah Medical School, will focus on two main goals. First, will be harnessing the modulation of RNA processing to increase the immunogenicity of "cold" cancers which lack genomic mutations, to exploit abnormal transcripts and evoke immune response; and second, enhancing the activity of the immune system by retargeting immune effector cells, modulating RNA splicing of key immune receptors and developing personalized mRNA vaccines.

This multi-disciplined team is composed of international leaders in the fields of RNA research, clinicians and biotech-pharma experts in RNA processing, RNA drug design and delivery, biocomputing and immuno-oncology: Wolf Prize Laureate Prof. Lynne Maquat of the University of Rochester; Prof. Maria Carmo Fonseca of the University of Lisbon; Prof. Juan Valcarcel of the Center for Genomic Regulation in Barcelona; Prof. Tanja DeGruijl of the University of Amsterdam; Prof. Niels Schaft of the University of Erlangen; Erez Levanon of Bar Ilan University; Seth Salpeter of Immunyx; Pablo Menendez of Jose Carreras Leukemia Institute in Spain; Evelien Smits of the University of Brussels; and Regine Shevach, Simon Geissler and Daniel Helman of Merck.

"CanceRNA will initially focus on two cancer types, acute myeloid leukemia, relevant for pediatric cancer, and uveal melanoma, both of which harbor splicing factor mutations and that are generally refractory to immunotherapy," said Professor Lotem. "Our hope is to utilize RNA-based therapeutics to overcome what until now, have been key barriers to successful anti-cancer immune responses. "

"The combination of experts from all over Europe in the fields of RNA biology, immunology, bioinformatics and drug transport will propel the development of the next generation of immunotherapy cancer treatments," added co-CanceRNA leader, Professor Rotem Karni, Chair of the Biochemistry and Molecular Biology Department at the Hebrew University-Hadassah Medical School.

Visit http://www.cancerna.info, for more information on CanceRNA.

About CanceRNA:

CanceRNA aims to impact the future of cancer treatment by developing and validating novel RNA-based therapeutics. This three-year project comprises multi-disciplinary activities to assess in-vitro and in-vivo validation, bioinformatics, delivery, and safety based on new and effective modalities of immunotherapy for cancer treatment. The CanceRNA team of researchers and scientists will be harnessing the modulation of RNA processing to enhance the accessibility and immune susceptibility of the tumor and its microenvironment, while working to enhance the activity of the immune system by retargeting immune effector cells, modulating RNA splicing of key immune receptors and developing personalized mRNA vaccines. For more information, http://www.cancerna.info.

About the Hadassah Cancer Research Institute:

Hadassah Cancer Research Institute (HCRI) is a translational research arm of Hadassah Medical Organization and Sharett Cancer Center in Jerusalem. Discoveries made in HCRI labs are a driver of clinical progress and beyond. With advanced labs focused on excellence areas of research in: Immuno Oncology, Cancer Epigenetics, Early Cancer Detection, Cell Therapy, Bioinformatics and a Biobank, our physicians and researchers are developing a multi-disciplined, multi-institution approach to discovering the next-generation treatments to fight cancer.

For additional information on the Hadassah Cancer Research Institute and CanceRNA, contact:

Amalia Herszkowicz, Chief Operating Officer, HCRI, Communication Officer, CanceRNAHadassah Cancer Research Institute (HCRI)[emailprotected]

View original content:https://www.prnewswire.com/news-releases/breakthrough-rna-based-anti-cancer-immunotherapy-treatments-being-developed-by-global-consortium-led-by-the-hadassah-cancer-research-institute-301627084.html

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Breakthrough RNA-Based Anti-Cancer Immunotherapy Treatments Being Developed by Global Consortium led by the Hadassah Cancer Research Institute -...

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

About the position

The postdoctoral fellowshipposition is atemporaryposition where the main goal is to qualify for work in senior academic positions.

We are seeking candidates with strong interest in bioengineering holding a PhD degree (or having submitted the PhD thesis) in biotechnology, biochemistry or related fields.

The research activities will be part of the PolySpore project funded by the NovoNordisk Foundation. In the project we will develop novel biological and hybrid materials as well as new data-storage concepts using bacterial spores. The researcher will work on genetically optimizing and manipulating spores of the Gram-positive bacterium Bacillus subtilis to present and produce load bearing proteins and characterize the resulting product, as well as to work on light driven catalysis using enzymes and upconverting nanoparticles.

Some aspects of the project are examined in collaboration with partners from France and Lithuania.

Your immediate leader is Assoc.Prof. Johannes Kabisch.

Duties of the position

Requiredselectioncriteria

The appointment is to be made in accordance withRegulations on terms of employment for positions such as postdoctoral fellow, Ph.D Candidate, research assistant and specialist candidate.

Preferred selection criteria

Personal characteristics

Emphasis will be placed on personal and interpersonal qualities.

Weoffer

Salary and conditions

As a Postdoctoral Fellow (code 1352) you are normally paid from gross NOK 563 500 per annum before tax, depending on qualifications and seniority. From the salary, 2 % is deducted as a contribution to the Norwegian Public Service Pension Fund

The period of employment is 2,5 years.

The engagement is to be made in accordance with the regulations in force concerningState Employees and Civil Servants, and the acts relating to Control of the Export of Strategic Goods, Services and Technology. Candidates who by assessment of the application and attachment are seen to conflict with the criteria in the latter law will be prohibited from recruitment to NTNU.

After the appointment you must assume that there may be changes in the area of work.

The position is subject to external funding.

It is a prerequisite you can be present at and accessible to the institution on a daily basis.

About the application

The application and supporting documentation to be used as the basis for the assessment must be in English.

Publications and other scientific work must follow the application.Please note that applications are only evaluated based on the information available on the application deadline. You should ensure that your application shows clearly how your skills and experience meet the criteria which are set out above.

If, for any reason, you have taken a career break or have had an atypical career and wish to disclose this in your application, the selection committee will take this into account, recognizing that the quantity of your research may be reduced as a result.

The application must include :

If all,or parts,of your education has been taken abroad, we also ask you to attach documentation of the scope and quality of your entire education.Description of the documentation required can befoundhere. If you already have a statement from NOKUT,pleaseattachthisas well.

Joint works will be considered. If it is difficult to identify your contribution to joint works, you must attach a brief description of your participation.

In the evaluation of which candidate is best qualified, emphasis will be placed on education, experienceand personal and interpersonalqualities.Motivation,ambitions,and potential will also countin the assessment ofthe candidates.

NTNU is committed to following evaluation criteria for research quality according toThe San Francisco Declaration on Research Assessment - DORA.

General information

Working at NTNU

NTNU believes that inclusion and diversity is a strength. We want our faculty and staff to reflect Norways culturally diverse population and we continuously seek to hire the best minds. This enables NTNU to increase productivity and innovation, improve decision making processes, raise employee satisfaction, compete academically with global top-ranking institutions and carry out our social responsibilities within education and research. NTNU emphasizes accessibility and encourages qualified candidates to apply regardless of gender identity, ability status, periods of unemployment or ethnic and cultural background.

The city of Trondheimis a modern European city with a rich cultural scene. Trondheim is the innovation capital of Norway with a population of 200,000.The Norwegian welfare state, including healthcare, schools, kindergartens and overall equality, is probably the best of its kind in the world. Professional subsidized day-care for children is easily available. Furthermore, Trondheim offers great opportunities for education (including international schools) and possibilities to enjoy nature, culture and family life and has low crime rates and clean air quality.

As an employeeatNTNU, you mustat all timesadhere to the changes that the development in the subject entails and the organizational changes that are adopted.

A public list of applicants with name, age, job title and municipality of residence is prepared after the application deadline. If you want to reserve yourself from entry on the public applicant list, this must be justified. Assessment will be made in accordance withcurrent legislation. You will be notified if the reservation is not accepted.

If you have any questions about the position, please contact Assoc.Prof. Johannes Kabisch, email: johannes.kabisch@ntnu.no.

If you think this looks interesting and in line with your qualifications, please submit your application electronically via jobbnorge.no with your CV, diplomas and certificates attached. Applications submitted elsewhere will not be considered.Upon request, you must be able to obtain certified copies of your documentation.

Application deadline: 17.10.2022

NTNU

NTNU - knowledge for a better world

The Norwegian University of Science and Technology (NTNU) creates knowledge for a better world and solutions that can change everyday life.

Department of Biotechnology and Food Science

Our activities contribute to increased exploitation of existing and new ingredients for sustainable food production as well as next-generation energy solutions and medical technology. We educate graduates for a wide range of careers in industry, public administration and academia.The Department of Biotechnology and Food Scienceis one of eight departments in theFaculty of Natural Sciences.

Deadline17th October 2022EmployerNTNU - Norwegian University of Science and TechnologyMunicipalityTrondheimScopeFulltimeDuration TemporaryPlace of service Glshaugen

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Postdoctoral Fellowship in Synthetic Biology job with NORWEGIAN UNIVERSITY OF SCIENCE & TECHNOLOGY - NTNU | 309904 - Times Higher Education

DPPH scavenging and metal chelating activity of sage

In order to support the protective role of sage against uranyl acetate toxicity, DPPH scavenging and metal chelating activities, which indicate antioxidant activity, were investigated and the results are given in Fig.2. DPPH is a stable free radical in aqueous solutions, and the decrease in the absorbance of the DPPH radical indicates antioxidant activity. Sage was determined to exhibit a dose-dependent increasing DPPH scavenging effect. DPPH scavenging activities of 200mg/mL sage, BHA and BHT were determined as 72.9%, 67.9% and 89.1%, respectively. The metal chelating activities of sage and standards were determined by evaluating their ability to compete with ferrozine for the ferrous ions. A dose-dependent increasing activity was also obtained in metal chelating activity. Metal chelating activities of 200mg/mL sage, BHA and BHT were determined as 82.8%, 76.3% and 88.5%, respectively. These results show that sage has a free radical scavenging activity that is higher than the standard antioxidant BHA and lower than BHT. Its high DPPH removal and metal chelating activity indicate the antiradical and metal chelating properties of sage, as well as its strong antioxidant capacity. There are also studies in the literature that draw attention to the similar features of sage. Emre et al.30 reported that different Salvia species grown in Turkiye exhibited metal chelating activity in the range of 45.080.48%. Roman et al.31 investigated the antiradical properties of S. officinalis extract and stated that it exhibited more than 85% DPPH removal activity. With the powerful antioxidant property, Sage has a protective role against much toxicity, and the results obtained in the Allium test in this study confirm this hypothesis.

DPPH scavenging (DSCA) and metal chelating activity (MCA) of sage.

The effects of uranyl acetate and sage application on selected physiological parameters are shown in Table 1. The maximum germination percentage, root length and weight gain were measured in the control group and Group II and Group III, which were exposed to two different doses of sage. No statistically significant difference was found between the physiological parameter values measured in these groups (p>0.05). In Group IV, in which 0.1mg/mL of uranyl acetate was administered, statistically significant decreases were found in all investigated physiological parameter values compared to the control group (p<0.05). It was observed that this decrease was approximately 2.1 times for germination percentage, about 7 times for root length and about 4.8 times for weight gain. The application of sage together with uranyl acetate caused a statistically significant (p<0.05) increase in the values of all investigated physiological parameters, although not as much as the control group. It was determined that these increases were more pronounced at the 380mg/L dose of sage. Compared to Group IV, germination percentage increased approximately 1.2 times, root length approximately 1.9 times and weight gain approximately 1.8 times in Group VI.

Although there is no comprehensive study in the literature on the effects of uranium or uranyl acetate application on the physiological properties of plants, there are some studies on the effects of other heavy metals. For example, avuolu et al.32 determined that Pb and Hg heavy metal application at 10 and 50ppm doses caused dose-dependent decreases in the germination percentage, root length and weight gain of Cicer arietinum L. seeds. They also reported that these decreases were more pronounced in the group exposed to the 50ppm dose of Hg. avuolu and Yaln33 determined that 25 and 50ppm doses of Al and Co application caused a dose-dependent decrease in the germination percentage, root length and weight of Phaseolus vulgaris L. cv. kidney bean seeds. They also observed that these decreases were more pronounced at the 50ppm dose of Al. Grel et al.34 observed that 2.4, 8.0 and 12.5mg/L Cr doses caused dose-related decreases in germination percentage, root length and weight gain in A. cepa. Girasun et al.35 determined that Pb application at 50, 100 and 200mg/L doses caused a dose-dependent decrease in physiological parameters such as germination percentage, root length and weight gain in A. cepa. Macar et al.36 found statistically significant reductions in germination percentage, root length and weight gain in A. cepa bulbs exposed to 5.5mg dose of Co for 72h.

In this study, it is thought that the abnormalities in physiological parameters as a result of uranium exposure are due to the reduction of A. cepa roots' intake of water and inorganic substances. Because it has been reported in the literature that high doses of heavy metal exposure in different plant species reduce the water and mineral substance uptake of the roots, and their productivity decreases by affecting the photosynthesis reactions and nitrogen metabolisms. On the other hand, it has been reported that exposure to heavy metals causes root, shoot, plant growth and plant weight reduction, deterioration of grana structure, inhibition of chlorophyll synthesis and respiration and development of apoptosis and necrosis processes in plants. ROS produced by heavy metals is shown as the main reason for the processes that encourage all these negative effects in the plant. Sage, which exhibits strong DPPH removal and metal chelating activity, protected against oxidative stress induced by uranium and exhibited a toxicity-reducing effect with its antioxidant property. It has also been stated in the literature that plants have developed some effective defense mechanisms to combat ROS-induced oxidative stress37. Therefore, it is considered that these defense mechanisms developed by A. cepa to prevent uranium from entering the cell may be another reason for the decrease in the investigated physiological parameter values. Because the excessive increases in the number/frequency of epidermis and cortex cells observed in the microscopic examination of root tip meristematic cells support this idea.

The genotoxicity induced by uranyl acetate application and the protective role of sage against this toxicity are shown in Figs. 3, 4 and Table 2. Statistically insignificant (p>0.05) MN formations were found in the control group and Group II and Group III, which were exposed to two different doses of sage. In addition, CAs in the form of a few sticky chromosome and unequal distribution of chromatin was detected in these groups, which was not statistically significant (p>0.05). On the other hand, the highest MI value (741.30, 747.90 and 743.80, respectively) was also determined in these groups. The application of 0.1mg/mL uranyl acetate caused the highest rate (82.40) of MN formation (p<0.05) in the root tip cells of the bulbs in Group IV, and promoted CAs such as fragment, vagrant chromosome, sticky chromosome, bridge and unequal distribution of chromatin and caused significant decreases (p<0.05) in the MI value. The greatest effect of uranyl acetate application on chromosomes occurred in the form of fragment formation. The application of sage together with uranyl acetate decreased the genotoxic effects of uranyl acetate, and caused a statistically significant (p<0.05) decrease in the frequencies of MN and CAs, and a significant (p<0.05) increase in the MI value, depending on the dose. It was determined that these alterations observed in the investigated genotoxic parameters were more pronounced in Group VI, where 380mg/L dose of sage was administered. Compared to Group IV, the frequency of fragment decreased approximately 1.5 times, the MN frequency decreased approximately 1.4 times, and the MI rate increased approximately 1.3 times in Group VI.

CAs induced by uranyl acetate. MN in interphase (a), fragment in metaphase (b), vagrant chromosome in anaphase (c), sticky chromosome in prophase (d), bridge in early anaphase (e), unequal distribution of chromatin in anaphase (f).

The effects of uranyl acetate and sage on DCN and MI (%). Group I: Control, Group II: 190mg/L sage, Group III: 380mg/L sage, Group IV: 0.1mg/mL uranyl acetate, Group V: 0.1mg/mL uranyl acetate+190mg/L sage, Group VI: 0.1mg/mL uranyl acetate+380mg/L sage. MI was calculated by counting 10,000 cells in each group. *indicates statistical difference between Groups I and IV, **indicates statistical difference between Groups IV and VI (p<0.05). DCN: dividing cell number, MI: mitotic index.

Although there is no comprehensive study in the literature on genotoxicity caused by exposure to uranium or uranyl acetate in plants, there are some studies conducted with experimental animals. For example, avuolu et al.38 observed MN formation in erythrocyte and buccal mucosal epithelial cells of Swiss albino mice exposed to 5mg/kg b.w of uranyl acetate by oral gavage for 5days. In addition, they reported a decrease in MI value with CAs in the form of break, fragment, gap, acentric and ring chromosomes in bone marrow cells. In addition, there are some studies in the literature investigating the genotoxicity induced by other heavy metal ions in plants. For example, avuolu et al.32 determined that exposure to Pb and Hg at two different doses (10 and 50ppm) caused an increase in the frequency of MN in C. arietinum root tip cells and promoted CAs in the form of sticky chromosome and bridge. avuolu and Yaln33 observed that exposure to Al and Co at 25 and 50ppm doses caused MN formation in P. vulgaris cv. kidney bean root cells. Grel et al.34 reported that administration of three different doses of Cr (2.4, 8.0 ve 12.5mg/L) caused a dose-dependent decrease in MI in A. cepa root tip cells. In addition, they found an increase in the frequency of MN and the numbers of CAs such as fragments, unequal distribution of chromatin, sticky chromosomes, bridges, reverse polarization and c-mitosis. Girasun et al.35 showed that exposure to three different doses (50, 100 ve 200mg/L) of Pb decreased the MI value, increased the frequency of MN, and caused damage in the form of fragments, adhesions, bridges and c-mitosis in A. cepa root tip cells, depending on the application dose. Macar et al.36 observed a decrease in MI, an increase in MN formation and an increase in the number of CAs in root tip cells of A. cepa, where 5.5mg of Co was applied. They also determined that Co application promotes CAs in the form of fragment, sticky chromosome, bridge, unequal distribution of chromatin, multipolar anaphase, nucleus damage, and irregular mitosis.

In our study, it is thought that the main reason for the decrease in MI value and the increase in the numbers of MN and CAs in Group IV treated with uranyl acetate may be due to the direct or indirect interaction of uranium with chromosomes. Because it has been reported in the literature that heavy metals disrupts the structure of DNA directly or indirectly by producing ROS, promoting DNA damages. On the other hand, some heavy metals have been reported to cause disruptions in DNA repair processes. For example, while Cr causes damage by reacting directly with DNA, As, Ni and Cd act by preventing the repair processes of DNA double-strand breaks. Damages such as MN, fragments, breaks, sister chromatid exchanges and variation are other CAs promoted by heavy metal ions39. The genotoxic and cytotoxic effects induced by uranyl acetate may be related to the occurrence of oxidative stress in general. Sage protects the integrity of the genome by reducing the oxidative load in the cell, especially with its strong metal chelating activity and antioxidant power. The reductions in MN and CAs frequencies observed in groups V and VI treated with sage+uranyl acetate confirm this idea.

The effects of uranyl acetate and sage application on selected biochemical parameters are shown in Fig.5. No statistically significant difference was observed between the root MDA levels and SOD and CAT activities of the control group and Group II and Group III exposed to two different doses of sage (p>0.05). Uranyl acetate application at 0.1mg/mL dose caused statistically significant (p<0.05) increases in root MDA level, which is an indicator of lipid peroxidation, and in SOD and CAT activities, which are antioxidant enzymes. Compared to the control group, these increases were found to be approximately 3.8 times for MDA level, approximately 3.2 times for SOD activity and approximately 2.7 times for CAT activity in Group IV. It was determined that the application of sage together with uranyl acetate again promoted statistically significant (p<0.05) decreases in MDA levels, SOD and CAT activities, depending on the dose. These decreases were even more pronounced in Group VI exposed to 380mg/L of sage. Compared to Group IV, approximately 2.1-fold decrease in MDA level, approximately 1.3-fold decrease in SOD activity and approximately 1.3-fold decrease in CAT activity was detected in Group VI.

Effect of uranyl acetate and sage application on selected biochemical parameters. Group I: Control, Group II: 190mg/L sage, Group III: 380mg/L sage, Group IV: 0.1mg/mL uranyl acetate, Group V: 0.1mg/mL uranyl acetate+190mg/L sage, Group VI: 0.1mg/mL uranyl acetate+380mg/L sage. * indicates statistical difference between Groups I and IV, ** indicates statistical difference between Groups IV and VI (p<0.05).

Although there is no comprehensive study in the literature of biochemical toxicity induced by exposure to uranium or uranyl acetate in plants, there are some studies with Swiss albino mice. avuolu et al.38 reported a significant increase in blood MDA levels and a significant decrease in GSH levels in Swiss albino mice exposed to 5mg/kg b.w of uranyl acetate by oral gavage for 5days. In a similar study, Yapar et al.40 found significant increases in MDA levels and significant decreases in GSH levels in liver and kidney tissues of Swiss albino mice exposed to 5mg/kg b.w of uranyl acetate. In addition, there are some studies dealing with the biochemical toxicity induced by other heavy metals other than uranium in plants. avuolu et al.32 reported that MDA levels in C. arietinum root tip cells exposed to Pb and Hg heavy metals at 10 and 50ppm doses increased dose-dependently, and these increases were even more pronounced at 50ppm doses of Hg. avuolu and Yaln33 stated that the application of Al and Co at two different doses (25 and 50ppm) caused dose-related increases in the MDA levels of P. vulgaris cv. kidney bean root cells, and these increases were higher et al. doses than at Co doses. Macar et al.36 observed that Co application at 5.5mg dose caused significant increases in MDA levels and SOD and CAT enzyme activities of A. cepa root tip cells.

MDA is a 3-carbon aldehyde, which is one of the most important markers of cell membrane damage, in other words, lipid peroxidation. Lipid peroxidation is a reaction caused by free radicals that cause oxidative damage of unsaturated fats. A free radical can then abstract the H atom and form an oxidized lipid free radical, producing a peroxyl radical. The peroxyl radical can remove an electron and produce a lipid hydroperoxide and another lipid free radical. This process can continue as a chain reaction. Since lipid hydroperoxide is unstable, it decomposes to form MDA and 4-hydroxy-2-nonenal products. In cases where the increase of free radicals in the cell, enzyme systems and antioxidant molecules in the cell are not sufficient for protection, these free radicals attack cell membranes, cause lipid peroxidation and increase MDA levels41. Therefore, the increase in MDA levels in A. cepa root cells treated with uranyl acetate can be explained by the fact that uranium causes free radical production and these free radicals cause damage to the membranes of the root cells.

SOD and CAT enzymes are known as antioxidants that prevent the formation of free radicals in the cell or eliminate or neutralize their effects. While the SOD enzyme neutralizes the superoxide radical, the CAT enzyme catalyzes the conversion of H2O2, which is highly toxic for the cell, into water and oxygen42. Therefore, the increase in SOD and CAT enzyme levels in A. cepa root cells exposed to uranyl acetate can be explained by the fact that uranium causes free radical production and increases SOD and CAT enzyme levels as a defense mechanism of the cell to minimize the harmful effects of free radicals. The fact that uranyl acetate increases MDA levels and induces antioxidant enzyme activities can be explained by triggering oxidative stress. The decrease observed in MDA, SOD and CAT levels in Group V and Group VI treated with sage+uranyl acetate shows that sage provides protection against the biochemical toxicity of uranyl acetate. This healing property is closely related to the antioxidant, antiradical and metal chelating activities of sage.

The effects of uranyl acetate and sage application on the root anatomy of A. cepa are shown in Fig.6 and Table 3. No damage was observed in the root meristem cells of Group II and Group III, which were exposed to two different doses of sage with the control group. In Group IV exposed to uranyl acetate at a dose of 0.1mg/mL, epidermis and cortex cell damage, as well as meristematic cell damage in the form of flattened cell nucleus were observed. Co-administration of sage with uranyl acetate caused reductions/improvements in the severity of observed meristematic cell damage by reducing the negative effects of uranyl acetate, depending on the dose. It was determined that this decrease in the severity level was more pronounced at 380mg/L dose of sage.

Meristematic cell damages induced by uranyl acetate. Normal appearance of epidermis cells (a), normal appearance of cortex cells (b), normal appearance of cell nucleus-oval (c), epidermis cell damage (d), cortex cell damage (e), flattened cell nucleus (f).

Although there is no study in the literature that deals with the anatomical changes caused by uranium or uranyl acetate exposure in plant root tip meristematic cells, there are some studies on the anatomical effects of other heavy metals. Grel et al.34 reported that 2.4, 8.0 and 12.5mg/L Cr doses caused anatomical damage in the form of cell deformation, thickening of the cortex cell wall, flattened cell nucleus and necrosis in root tip meristematic cells of A. cepa. They also stated that the severity of these damages was dose dependent. avuolu et al.43 observed anatomical damage such as cell deformation, necrosis, flattening cell nucleus, thickening of the cortex cell wall, inclearly vascular tissue and accumulation of some substances in cortex cells in A. cepa root tip meristematic cells exposed to Hg at 25, 50 and 100mg/L doses. Girasun et al.35 detected cell damage such as thickening of the cortex cell wall, cell deformation, inclearly vascular tissue and necrosis in A. cepa root tip meristem cells of 50, 100 and 200mg/L doses of Pb exposure, the severity of which increased with the application dose. Macar et al.36 reported that 5.5mg Co dose promoted damages such as epidermis cell deformation, thickening of the cortex cell wall and flattened cell nucleus in A. cepa root tip meristematic cells.

This suggests that this epidermis and cortex cell damage induced by uranium occurs as a result of the defense mechanisms developed by plants against heavy metal ions. Because the roots have increased the number and frequency of the epidermis and cortex cells in order to prevent uranium from entering the cell, and these damages may have occurred as a result of the compression/suppression of the cells. The information in the literature that plants develop different defense mechanisms against heavy metal toxicity, such as accumulation, storage and crystallization of metals in certain regions, or changes in the cell membrane and cell wall, increase in vacuole numbers and metal-binding protein synthesis44, supports our this idea.

In recent studies, different plant extracts such as lycopene, carotene, Ginkgo biloba L., green coffee, green tea and stinging nettle are used to reduce toxicity promoted by toxic agents such as heavy metal ions. In this study, sage treatment provided significant protection against the physiological, biochemical, cytogenetic and anatomical abnormalities exhibited by the application of uranyl acetate in the A. cepa root tip cells. It provided improvement in germination-related parameters such as root length and weight gain, and decreased MN and CAs frequencies, which were detected at high rates after uranyl acetate application. These improvements increased depending on the dose and the highest protection was obtained at the dose of 380mg/L. In this study, it was determined that sage has antiradical property and scavenges the DPPH radical at a rate of 72.9%. Sage is a powerful antioxidant compound, which also exhibits an important metal chelating activity. These powerful properties of sage are related to the active ingredients it contains. The greatest role in the protective role of sage is the antioxidant activity exhibited due to phenolic compounds such as carnosic acid, carnosol, rosmarinic acid and camphor in the content. There are some studies in the literature focused on the antioxidant role of sage. For example, Lima et al.45 investigated the antioxidant potential of traditional water infusion (tea) of sage in vivo in mice and rats. In conclusion, it was determined that replacing the water in the diet of rodents with sage for 14days did not affect the body weight and food consumption of the animals. They also reported that sage did not cause liver toxicity, liver GST activity was increased in rats (24% rate) and mice (10% rate) drinking sage, on the other hand, sage caused an improvement in the antioxidant status of hepatocytes, increased GSH levels and provided a protection against lipid peroxidation. Horvthov et al.46 investigated the protective effect of sage extract against oxidative stress to which liver cells of SpragueDawley rats are exposed. As a result, no negative effects were observed on basal DNA damage levels and SOD activities in hepatocyte cells of animals that drank sage for 14days, and no changes were detected in the biochemical parameters of blood plasma. On the contrary, they determined that sage extract significantly increased GPx activity, decreased DNA damage levels caused by oxidants, and provided antioxidant protection by increasing GSH levels. Alshubaily and Jambi47 investigated the possible protective role and antioxidant activity of sage extract against metabolic disorders caused by hypercholesterolemic diet in heart and testicular tissues of rats. In conclusion, they determined that the hypercholesterolemic diet significantly increased serum lipid content, cardiac marker enzyme activities, MDA levels, and significantly decreased high-density lipoprotein-cholesterol levels in testes and heart tissues. They observed that the co-administration of hypercholesterolemic diet and sage extract reduced the damage caused by the hypercholesterolemic diet by causing a decrease in lipid peroxidation, induction of heart and testis functions, and increased activity. They reported that essential oil, phenolic contents and other antioxidant components contained in sage extract were effective in this.

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New research evaluates how rapid tests will perform when challenged with future SARS-CoV-2 variants.

The availability of rapid antigen tests has significantly advanced efforts to contain the spread of COVID-19. But every new variant of concern raises questions about whether diagnostic tests will still be effective.

The new study in Cell attempts to answer these questions.

The researchers developed a novel method for evaluating how mutations to SARS-CoV-2 can affect recognition by antibodies used in rapid antigen tests.

Because most rapid antigen tests detect the SARS-CoV-2 nucleocapsid protein (N protein), the team directly measured how mutations to the N protein affected diagnostic antibodies ability to recognize their target.

Based on our findings, none of the major past and present SARS-CoV-2 variants of concern contain mutations that would affect the capability of current rapid antigen tests to detect antibodies, says first author Filipp Frank, an assistant professor in the department of biochemistry at Emory University. Further, these data allow us to look one step ahead and predict test performance against almost any variant that may arise.

The study used a method called deep mutational scanning to evaluate all possible mutations in the N protein in a single, high-throughput experiment. Researchers then measured the impact of the mutations on their interaction with antibodies used in 11 commercially available rapid antigen tests and identified mutations that may allow for antibody escape.

Accurate and efficient identification of infected individuals remains a critically important strategy for COVID-19 mitigation, and our study provides information about future SARS-CoV-2 mutations that may interfere with detection, says senior study author Eric Ortlund, a professor in the department of biochemistry. The results outlined here can allow us to quickly adapt to the virus as new variants continue to emerge, representing an immediate clinical and public health impact.

Findings show that its relatively rare for variants to have mutations to the N protein that allow them to evade diagnostic tests, but there are a small proportion of sequences that could affect detection. Researchers, public health officials, and test manufacturers can use these data to determine if a diagnostic test needs to be evaluated for its ability to detect these mutations or to inform future test design.

Considering the endless cycle of new variants, the data from this study will be useful for years to come, says Bruce J. Tromberg, director of the National Institute of Biomedical Imaging and Bioengineering (NIBIB) and lead for the Rapid Acceleration of Diagnostics (RADx) Tech program at National Institutes of Health.

While many variants of concern contain multiple mutations to the N protein, the study authors note that their method does not evaluate how multiple mutations could affect diagnostic antibody recognition, representing a limitation of the study.

Support for the project came from NIBIB as part of the RADx initiative.

Source: Emory University

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Will rapid COVID tests be able to detect new variants? - Futurity: Research News

What is serum?

When blood clots, it separates into two parts a clear pale yellow liquid called serum and a small solid portion composed of blood cells.

Serum is collected by placing a tube of clotted blood in a machine called a centrifuge, which spins the blood very quickly in a small circle, forcing the cells to the bottom of the tube and allowing the serum to sit on top. The serum is then lifted off the top and placed in a fresh tube for testing.

Serum biochemistry refers to the chemical analysis of serum. There are many substances in serum, including proteins, enzymes, lipids, hormones, etc. Testing for these various substances provides information about the organs and tissues in the body as well as the metabolic state of the animal. If a test result is abnormal, it may indicate that disease is present. Further assessment of the test results may offer clues about which organ system is affected and also the nature and severity of the disorder.

There are too many substances in serum to consider testing all of them each time a pet gets sick, so tests for the various substances are arranged into smaller groups, called serum biochemistry panels or profiles. Each panel or profile is a selected group of biochemistry tests designed to investigate a specific interest or concern.

For example, a general health profile would include a wide range of tests with the aim of assessing a variety of organs, while a kidney profile would include a smaller number of tests related specifically to the kidney, and so on. A profile can be simple or complex and your veterinarian will determine which profile is best suited to the needs of your pet.

Proteins (total protein, albumin, globulin). The two main types of protein found in blood are called albumin and globulin. These proteins can be measured individually, or combined into a single test called total protein, which measures all protein in the sample. Albumin levels can indicate if a pet is dehydrated, and can provide information about the function of the liver, kidneys, and digestive system. Globulin levels reflect underlying inflammation and/or antibody production. Increased levels of globulins are often associated with infectious diseases, immune-mediated disease, and some types of cancer.

Liver Enzymes (ALT, ALP). There are many different liver enzymes, but the two that appear in most profiles are alanine aminotransferase (ALT), and alkaline phosphatase (ALP). The first enzyme is typically found when the cells of the liver are stressed or damaged. The second enzyme is generally increased when bile flow in the liver is reduced.

Bilirubin is a pigment produced primarily in the liver that is associated with the breakdown of hemoglobin from red blood cells. Bilirubin is stored in the gall bladder as a component of bile. Increases in bilirubin are associated with increased red cell destruction or decreased bile flow through the liver.

Kidney Tests (urea, creatinine). The two substances most commonly measured to assess kidney function are urea (also called blood urea nitrogen or BUN) and creatinine. Urea is a by-product of protein breakdown; it is produced in the liver and excreted from the body by the kidney. Increases in BUN may indicate dehydration, gastrointestinal bleeding, cardiac disease, or primary kidney disease. Decreases in BUN are associated with over hydration, liver failure, or reduced protein intake in the diet. Creatinine is a by-product of muscle metabolism and it is excreted entirely by the kidney. Increased levels of creatinine indicate decreased kidney function.

Pancreatic Enzymes (amylase, lipase, pancreatic lipase immunoreactivity). Two commonly measured pancreatic enzymes are amylase and lipase.Increases in these enzymes may occur when the pancreas is inflamed, although they can also be elevated with kidney or intestinal disease, and when certain drugs are used. They are not very reliable indicators of pancreatitis. A newer test for pancreatic inflammation called pancreatic lipase immunoreactivity (PLI) is more reliable because it rises only with pancreatic inflammation (see handouts "Pancreatitis in Cats - Pancreas-Specific Lipase" and "Pancreatitis in Dogs - Pancreas-Specific Lipase"). Certain laboratories run variations of this test called spec cPL, fPL or PSL.

Glucose (blood sugar). A persistently high blood sugar is associated with diabetes mellitus, also known as "sugardiabetes." A temporary rise in blood sugar is commonly found in cats associated with the excitement of visiting the veterinarian; this stress response can make it difficult to diagnose diabetes mellitus in some cats.Low blood sugar can be found in newborn animals, some very small breeds of dogs, and high performance dogs, such as hunting dogs, that exercise extensively. Low blood sugar is also associated with some types of cancer, bacterial infections, or insulin overdose in diabetic patients. False low glucose values often occur when a blood sample is not stored correctly after collection.

Calcium and Phosphorus. These minerals are present in tiny amounts in blood and changes, either up or down, may be associated with a variety of diseases or conditions. For example, persistently high calcium levels may indicate the presence of kidney disease, cancer, or disease of the parathyroid glands, while low calcium levels may be due to pancreatitis, antifreeze poisoning, or disease of the parathyroid gland. High phosphorus levels are associated with kidney failure and some nutritional problems. Low phosphorous level can occur with dietary problems, gastrointestinal disease, and kidney disease etc.

Muscle Enzymes (CK, AST, ALT). Creatinine kinase (CK) is the enzyme most frequently measured to assess injury. Of lesser importance are the enzymes aspartate aminotransferase (AST) and alanine aminotransferase (ALT), which are also used to assess liver function. Increased muscle enzyme levels are often found with muscular activity (exercise, exertion, convulsions etc.), as well as trauma and muscle inflammation.

Cholesterol is produced in the liver as part of fat metabolism. Increases in cholesterol are associated with hormonal and metabolic diseases, liver disease, and serious kidney disease.

Electrolytes. The most important electrolytes are potassium, chloride, sodium, and bicarbonate. These substances are present in blood in small quantities, and each electrolyte has a different role to play in the body. Collectively, electrolytes help to maintain blood and tissue fluids in balanced state. Disturbances in electrolytes are often caused by vomiting, diarrhea, and kidney disease, and accompany many serious metabolic disorders.

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Serum Biochemistry | VCA Animal Hospital

The Master of Science in Biochemistry & Molecular Biology at Georgetown University is a basic science program that infuses core concepts of biochemistry and molecular biology as applied to biomedical sciences and biotechnology, providing students with a rigorous and challenging curriculum. Graduates from the program excel in various career paths with government agencies, academic institutions, research laboratories, and biotechnology companies. Alumni have also continued their education by pursuing doctoral, medical, and law degrees, using the skills and training at Georgetown University to propel their future academic and research careers.

Core concepts and skills are taught through required core courses, advanced electives, special topics courses, and a 4 credit internship. At least 30 graduate credits with a cumulative GPA of 3.0 or greater are required for the M.S. degree. Our courses expose students to advanced methods in biochemistry, molecular biology, and cell biology, laboratory research, and literature-based research and include a significant number of hands-on lab-based courses that develop research expertise.

Our program offers a well-organized, intensive capstone internship program that culminates in students presenting their research at tri-annual poster presentation sessions. The internships are done with research mentors in various GUMC laboratories on-campus, or off-campus in government agencies such as NIH and FDA or biotechnology companies.

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Prostate-specific membrane antigen, or PSMA, has made headlines in the past several years with several important clinical trials demonstrating both diagnostic and therapeutic benefits. PSMA, a transmembrane glycoprotein, is frequently overexpressed in the prostate cancer epithelium, allowing it to serve as a target lesion for biomarkers for diagnostic or therapeutic purposes.1 Examples of therapeutic compounds include lutetium-177-PSMA-617 (177Lu-PSMA-617), which was reported on earlier in 2021 for its role in the treatment of patients with metastatic castration-resistant prostate cancer.

To review, when a biomarkerfor diagnostic or therapeutic purposesbinds to the PSMA receptor, it triggers an endocytotic process that facilitates development of higher concentrations of the bound biomarkers inside the prostate cancer cells.2 On the diagnostic side, there are generally 2 classes of PSMA-based biomarkers that have been widely adopted into use: gallium-68 (68Ga)-PSMA-11 (also known as gozetotide) and fluorine-18 (18F)-based PSMA compounds.

The clinical impact of PSMA-based imaging has been documented by several studies, including a meta-analysis demonstrating that attaining a PSMA-based imaging studyespecially in patients with suspected biochemical recurrence after primary therapycan often lead to a change in the management approach. In a meta-analysis of 1,309 patients, Perera et al demonstrated that 68Ga-PSMA-11 scans had a 76% positivity rate for biochemical recurrence and led to a change in management 54% of the time.3 Despite many positive reports showing promising uses of 68Ga-PSMA-11, geographic availability remains a primary limitation because of its short 68-minute half-life, which restricts its ability to become commercially available and therapeutically viable in parts of the country where access is an issue.4

The primary alternative to 68Ga-PSMA-11 using the PSMA biomarker is the 18F class of compounds, which has slowly gained wide recognition. The CONDOR trial investigated the use of 18F-DCFPy (Pylarify; piflufolastat positron emission tomography/computed tomography [PET/CT]) in patients thought to have biochemical recurrence after primary therapy (prostatectomy or radiation).5 Of the 208 patients enrolled in the trial, the authors reported a 63.9% change in management after Pylarify imaging, which is in line with the data in published reports of 68Ga-PSMA-11.5

At the 2022 American Urological Association Conference (AUA 2022), results of the phase 3 SPOTLIGHT study were presented that demonstrated the efficacy of 18F-rhPSMA-7.3 for diagnostic imaging in patients with prior localized therapy for prostate cancer who have concern about biochemical recurrence. The rhPSMA class is a subclass of PSMA compounds that allows for faster radiolabeling and decreased urinary clearance compared with 68Ga-PSMA-11.6,7 The latter point has been thought to be a significant impairment to image interpretation owing to the blurring of images produced by concentration of the compound within the urinary bladder.

Several other 18F-based PSMA ligands have been developed, including 18F-DCFPyL and 18F-rhPSMA-7. Proposed benefits of the 18F class of biomarkers, compared with 68Ga-PSMA-11, include its longer half-life (120 minutes), which facilitates simplified transport protocols, and therefore greater patient access, and makes higher quantities of production in cyclotrons (particle accelerators that produce radioactive isotopes) possible.6 Furthermore, 18F-based imaging is also thought to provide greater spatial resolution, leading to fewer blurring artifacts on the final imaging studies.

The SPOTLIGHT study (NCT04186845),8 which was reported at AUA 2022 and covered in a previous issue of GU Oncology Now, sought to explore the utility of 18F-rhPSMA-7.3 in the biochemical recurrence setting by identifying patients with increasing prostate-specific antigen (PSA) levels after primary treatment. All patients enrolled in SPOTLIGHT had negative results on conventional imaging, and all images were interpreted by 3 separate radiologists. The exploratory analysis demonstrated that obtaining 18F-rhPSMA-7.3 imaging at the time of concern for biochemical recurrence led to a 45% to 47% rate of upstaging. An interesting fact of note was that patients undergoing primary radiotherapy had higher rates of positivity in the prostate bed compared with those who underwent prostatectomy although their pelvic lymph nodes and extrapelvic regions were similar.

In a recent issue of European Urology, the authors of a double-blind phase 3 randomized controlled trial compared 68Ga-PSMA-11 with 18F-PSMA-11.9 In their introduction, they explain many of the limitations of 68Ga, including its short half-life and the cost of generating the compound. The trial, conducted out of Ghent University Hospital, Belgium, enrolled patients thought to have biochemical recurrence after primary therapy or prostate cancer confirmed by biopsy. Patients with limited renal function (serum creatinine >2 or estimated glomerular filtration rate <30) were excluded.

By design, all patients underwent both 18F-PSMA-11 and 68Ga-PSMA-11 scans. The primary endpoint was noninferiority of 18F-PSMA-11 compared with 68Ga-PSMA-11. The authors also investigated several secondary endpoints, including the number of positive PET scans, lesions suspicious for prostate cancer, and correlation of PET imaging with follow-up data. The trial had significantly more patients with concern for biochemical recurrence (n=66) compared to primary prostate cancer (n=19); however, other characteristics, including median age, were similar between the 2 groups.

In regard to the primary endpoint, the 2 imaging modalities had the same positivity rate (67%; 55 of 82 patients with positive scans). Secondary endpoints demonstrated no superiority of 18F- over 68Ga-based imaging, but the authors did note that 18F-PSMA-11 scans had a higher rate of equivocal lesions in the axial skeleton. Specifically, they noted that 18F-PSMA-11 scans demonstrated additional lesions in skeletal tissue in 9 patients and in lymph nodes in 4 patients. They attributed this to a known downside of 18F radioisotopes but explained that this hypersensitivity may be useful in detecting small positive lesions in patients with very low PSA values in whom clinicians might have concern for recurrence. The authors noted in their conclusion that this was the largest prospective phase 3 trial comparing 18F-PSMA-11 and 68Ga-PSMA-11 and suggested that 18F-PSMA-11 is a cost-effective alternative to 68Ga-PSMA-11 that achieves similar results.

Other ongoing clinical trials in progress will help elucidate the role of 18F-PSMA-11 in the management of prostate cancer. One trial of interest is an investigation into the role of 18F-PSMA scans in the primary localized treatment setting (NCT04461509). Another is a phase 2 trial being conducted at the University of Alberta, which is exploring the role of 18F-PSMA imaging in locoregional staging of patients undergoing radical prostatectomy for clinically significant prostate cancer (NCT05141760). These investigations and others will continue to provide valuable insights into the role and utility of PSMA-targeted imaging in the treatment of patients with prostate cancer.

References

Excerpt from:
Introduction to 18F-PSMA: An Alternative Radioisotope for PSMA-based Imaging - DocWire News

Media Contacts Julie Kiefer

Associate Director, Science Communications, University of Utah HealthEmail: julie.kiefer@hsc.utah.eduPhone: 801-587-1293

Aug 08, 2022 10:00 AM

A University of Utah Health-led multi-institutional research center that studies the inner workings and vulnerabilities of HIV, the human immunodeficieny virus that causes AIDS, recently received a five-year, $28 million grant renewal from the National Institutes of Health.

Since its founding in 2007, the CHEETAH Center for Structural Biology of HIV Infection Restriction and Viral Dynamics has published more than 300 research papers that have led to a better understanding of HIV and its potential treatments.

Wesley Sundquist, Ph.D., the centers director and professor and chair of the Department of Biochemistry at U of U Health, is leading 20 research teams from 12 institutions. With the grant renewal, the researchers will focus on:

The outstanding science stemming from this program is changing an understanding of HIV/AIDS, other viral diseases, and cellular biology, enabling the development of novel therapeutics such as lenacapavir and D-peptide inhibitors, says Rachel Hess, M.D., associate vice president for research at U of U Health, referring to two investigational drugs with roots in CHEETAH.

From deep understanding to investigational drugs

Just a half-century ago, HIV infection almost inevitably led to serious illness and death. Todays antiretroviral therapies can suppress the virus and prevent symptoms, but improvement is still needed. If these drugs arent taken daily, the virus can rebound and acquire drug resistance. The medicines can also cause difficult side effects. The underpinnings for two new investigational drugs that could help circumvent these issues are based on years of research by CHEETAH scientists.

Research from Sundquist; Christopher Hill, D.Phil, distinguished biochemistry professor at U of U Health; and other CHEETAH Center labs on the HIV capsida structure they found is vital for different steps of the HIV life cyclelaid the groundwork that led the pharmaceutical company Gilead Sciences to identify the capsid inhibitor, lenacapavir. This investigational drug is now in phase 3 clinical trials and is already showing great promise as a potent, long-acting treatment.

Taking a different approach, Michael Kay, M.D., Ph.D., CHEETAH investigator and biochemistry professor, and Debra Eckert, Ph.D., biochemistry research assistant professor, used synthetic chemistry to design a D-peptide inhibitor called CPT31 that jams HIVs infection machinery. The molecule is now in phase 1 clinical trials sponsored by Navigen, Inc.

Often people forget that drug development builds from basic research, Sundquist says. These are two more cases where that has happened, and it is very satisfying.

Learning lessons from HIV

CHEETAH continues to bring an understanding of HIV, related viruses, and host biology in new directions through collaborations between its scientists, who come from a variety of disciplines. "The CHEETAH Center is doing exciting, interdisciplinary science in a collaborative environment that allows us to accomplish projects that wouldn't otherwise be possible in any single lab," says Pamela Bjorkman, Ph.D., a professor of biology and biological engineering at Caltech.

NelsElde, Ph.D., professor of human genetics at U of U Health, turns to evolution for inspiration, noting that many animals are not as susceptible as humans to disease caused by HIV. He is collaborating with fellow CHEETAH scientists to explore whether a gene found in mice and squirrel monkeys that prevents HIV from exiting cells after replicating could become the basis for anew type of antiviral.

Nature has done seemingly countless billions of experiments that got us to where we are today, Elde says. Can we learn from whats happened and borrow and deploy them in ways that are useful?

By contrast, Owen Pornillos, Ph.D., a CHEETAH investigator from the University of Virginia who received his doctorate from the U, takes advantage of his biochemistry expertise to take a different approach. In a collaborative project with several CHEETAH Center members, he is removing the virus from the complex environment of the host cell and bringing it to the test tube. By adding back specific ingredients a few at a time, the team is identifying key virus and host cell components that are essential for early stages of viral infection and replication. Combining this approach with new microscope technologies is allowing them to visualize these steps with unprecedented clarity.

CHEETAH is committed to doing excellent science and is always planning for where we envision the field will be five years from now, Pornillos says. Its exciting to be a part of it.

These diverse tactics are providing valuable insights into virology and biology, and uncovering targets for new types of therapeutic intervention.

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Research News iii

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U of U Health-Led Research Awarded $28 Million to Explore HIV's Inner Workings and Vulnerabilities - University of Utah Health Care

The demographic characteristics of the subjects

Table 1 indicates the demographic characteristics for all indices. A total of 22,509 subjects aged 50 years were included in the final analysis. The final dataset consisted of 21,426 subjects without MIAP (men = 8869, women = 12,557) and 1083 subjects with MIAP (men = 583, women = 500). The prevalence of MIAP in Korean adults aged 50 years was 4.81% (6.57% for men and 3.98% for women). All other indices analyzed in this study except for ischemic heart disease (IHD) family history (p = 0.588), systolic blood pressure (SBP, p = 0.146), and BMI (p = 0.721) showed statistically significant differences between men and women. We also analyzed the difference between the non-MIAP and MIAP groups. Among the demographic factors, age, education level, occupation, and household income, but not residential area, showed significant differences between the two groups in both men and women. The average age of the MIAP group (men: 65.88 0.46, women: 68.7 0.42) was older than that of the non-MIAP group (men: 60.84 0.12, women: 61.53 0.11). The MIAP group was significantly more likely to have a lower educational level and household income and a higher unemployment rate than the non-MIAP group. In particular, the difference between the non-MIAP and MIAP groups in these indices tended to be more prominent in women than in men. Among the health behavior factors, stress showed a significant difference only in women. The prevalence of 'slight' was the highest in both the non-MIAP group and the MIAP group, but the percentage of very' tended to be higher in the MIAP group than in the non-MIAP group. In addition, alcohol consumption showed significant differences in both men and women, and the MIAP group was more likely to have lower alcohol consumption than the non-MIAP group. Smoking status showed no significant difference between the two groups in both men and women. Among the preliminary health examination and disease-related indices, IHD family history, hypertension, diabetes, and hypercholesterolemia showed significant differences between the two groups in men and women, whereas hypertriglyceridemia showed no significant difference in men (p = 0.095) or women (p = 0.181). In particular, the IHD family history in the MIAP group tended to be 63.10% greater in men and 110.60% greater in women than in the non-MIAP group. Among the health examination-related indices, in men, diastolic blood pressure (DBP), height, BMI, WC, WHtR, glucose, total cholesterol, triglycerides, HDL-C, hemoglobin, hematocrit, blood urea nitrogen (BUN), creatinine, white blood cells (WBCs), red blood cells (RBCs), and platelets showed significant differences between the two groups. In women, SBP, DBP, height, BMI, WC, WHtR, glucose, total cholesterol, HDL-C, aspartate aminotransferase (AST), hemoglobin, hematocrit, BUN, creatinine, WBC, RBC, and platelet showed significant differences between the two groups. SBP was significantly different between the two groups only in women, and the MIAP group was higher than the non-MIAP group, whereas DBP was lower in the MIAP group than the non-MIAP group in men and women. The MIAP group tended to be shorter and have higher weight than the non-MIAP group, but there was no substantial difference. On the other hand, WC was more likely to be larger in the MIAP group than in the non-MIAP group. Although most biochemical indices did not differ significantly between the two groups, the MIAP group was more likely to have lower total cholesterol than the non-MIAP group in men and women.

Tables 2 and 3 show the associations between MIAP and blood pressure, anthropometric indices, and biochemical indices in Korean men and women aged 50 years. Of all indices, total cholesterol showed a more strongly negative association with MIAP than all other indices in men (OR = 0.401 [0.3540.453], p < 0.001) and women (OR = 0.472 [0.4130.539], p < 0.001) in the crude analysis. In addition, this association was strongly maintained in men (adjusted OR = 0.436 [0.3840.495], adjusted p < 0.001) and women (adjusted OR = 0.541 [0.4750.618], adjusted p < 0.001) after adjusting for age, residential areas, education, occupation, household incomes, stress, alcohol consumption, smoking status, IHD family history, and BMI. In addition to total cholesterol, creatine and platelets showed significant associations with MIAP in men and women in the crude and adjusted analyses. Nevertheless, except for these three variables, the association between MIAP and all other variables showed sex differences.

Among blood pressure-related variables, in men, only DBP showed a negative association with MIAP in the crude (OR = 0.614 [0.5510.685], p < 0.001) and adjusted analyses (adjusted OR = 0.719 [0.6380.809], adjusted p < 0.001), whereas only SBP showed a significant association with MIAP in the crude (OR = 0.838 [0.7510.933], p < 0.001) and adjusted (adjusted OR = 1.133 [1.0191.259], adjusted p = 0.022) analyses in women. Of the obesity indices, WC and WHtR showed a significant association with MIAP in the crude and adjusted analyses in men. In particular, WHtR (adjusted OR = 1.325 [1.0821.623], adjusted p = 0.007) showed a more significant association with MIAP than WC (adjusted OR = 1.290 [1.0721.553], adjusted p = 0.007). In contrast, in women, all indices showed a significant association in the crude analysis, but there was no association between MIAP and any obesity index in the adjusted analysis. Among biochemical indices, total cholesterol, creatine, and platelets were associated with MIAP in men and women, but other variables except for these variables showed sex differences. In men, hemoglobin (adjusted OR = 0.749 [0.6770.830], adjusted p < 0.001), hematocrit (adjusted OR = 0.777 [0.7040.858], adjusted p < 0.001), BUN (adjusted OR = 1.077 [1.0001.160], adjusted p = 0.049), and RBC (adjusted OR = 0.787 [0.7090.873], adjusted p < 0.001) were associated with MIAP in the crude and adjusted analyses, whereas in women, only AST (adjusted OR = 1.072 [1.0011.149], adjusted p = 0.047) showed an additional association with MIAP in the crude and adjusted analyses.

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Association of myocardial infarction and angina pectoris with obesity and biochemical indices in the South Korean population | Scientific Reports -...

The Summer Scholars Program in Genome Sciences & Medicine, a collaboration between the Duke Program in Precision Medicine, the Duke Center for Genomic and Computational Biology (GCB), andNorth Carolina Central University (NCCU), concluded the 10-week program last week in Durham, North Carolina.

This summer, eight scholars from across the country were paired with a faculty research mentor to learn laboratory skills, designing a research project, and effectively presenting future research.

This summer program has provided me with the skills I need for the rest of my research career, said Paola J. Maldonado, a rising sophomore from the University of Puerto Rico. Working in research is what I want to do, and this experience really solidified that for me. Maldonado was mentored by Jen-Tsan Ashley Chi, PhD, associate professor of molecular genetics and microbiology and assistant professor of medicine in the division of rheumatology and immunology.

Brielle-Anne Michel, a rising junior at Wake Forest University studying biochemistry and molecular biology, was mentored by HiroakiMatsunami, PhD, professor of molecular genetics and microbiology and neurobiology at Duke. The most exciting part of this program was getting to work with the scientific technologies Ive learned about in undergrad classes but havent seen firsthand, she said. I had mentorsshow me the steps to take, and I was able to do several trials completely by my myself, which was exciting.

Students experienced 10 weeks of everything from working in labs, weekly seminars with Duke professors and graduate student mentors, and tips on networking. Among the many skills obtained, they learned more about how to form research abstracts, posters, writing personal statements and CVs, and presenting their research effectively.

The Summer Scholars program gave me my first opportunity to do hands-on research, said Sydney Vander, a pre-med chemistry major at Xavier University of Louisiana. Thanks to this program, I was able to develop important skills, such as, critical thinking, problem solving, and effective communication. Vander aspires to be a physician and shared how the Summer Scholars program helped her realize that she can incorporate research into her future career path. One day she hopes to perform clinical research while also providing care for patients.

The Summer Scholars Program in Genome Sciences & Medicine is supported by an R25 grant by the National Human Genome Research Institute at NIH and is designed for full-time first- and second-year underrepresented in STEMstudents at any college or university.

A special thanks to 2022 faculty mentors, Ashley Chi, PhD; Ornit Chiba-Falek, PhD; Lindsey Constantini, PhD (NCCU); Charlie Gersbach, PhD; Paul Magwene, PhD; Alex Marshall, PhD (NCCU); Hiro Matsunami, PhD; and Anne West, MD, PhD

Learn more about the Summer Scholars Program in Genome Sciences & Medicine

View all photos from the Summer Scholars Poster Session on July 29, 2022

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Summer Scholars leave Duke with a once-in-a-lifetime research experience - Duke University

As the 2022 harvest ramps up in earnest,BSG Wine, a leading winemaking ingredients and product supply group headquartered in the Napa Valley since 2007, is uniquely positioned to equip the winemaking community with what it needs to for a spectacularly successful season.

BSG is the leading U.S. distributor of the MegaQuant Wave Spectrophotometer, a powerful, user-friendly instrument ideal for laboratories performing up to 200 analyses per day.

BSG wants winemakers and lab technicians to know that its MegaQuant Wave Starter Pack offers products that are more cost-effective than any external laboratory through pre-programmed protocols for wine tests that require no manual manipulation and are analysis-ready right out of the box.

The MegaQuant Wave Starter Pack features the MegaQuant Wave Spectrophotometer with a streamlined design offering a touch screen interface, superb optics, on-board curve fitting software and built in printer to meet the requirements of most winery labs.

In addition, the MegaQuant Wave Starter Pack includes pre-programmed protocols for measuring volatile acidity, fructose, glucose and sucrose, primary amino nitrogen, ammonia, L-arginine and urea ammonia, as well as a host of other analytes.

The MegaQuant Wave is available as a single item spectrophotometer (D-MQWAVE-1) or as part of theMegaQuant Wave Starter Pack.

The MegaQuant Wave Spectrophotometer, a stand-alone, bench top unit with specific, built-in instruction, automatically calculates results usingMegazyme biochemical assay kits.

In addition to the spectrophotometer, the MegaQuant Wave Starter Pack comes equipped with:

Any winery could go from no lab or a rudimentary lab to full lab capability with the addition of the MegaQuant Wave Spectrophotometer and our MegaQuant Wave Starter Pack, notes James Kress, BSGs Technical Sales Manager for Wine in the Northeastern U.S.

An extensive, web-based knowledge program that provides specific information about each analytic methodology, complete with user-friendly training manuals and instructional videos, supports The MegaQuant system.

For more specifications and orders, go to:bsgwine.com/megazyme-assay-kits.

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Precision Lab Testing Made Easy by Innovative Wave Spectrophotometer and Pre-Programmed Biochemical Assay Kit - wineindustryadvisor.com

How can we create a diverse network of colleagues? That deceptively simple question sparked an "unforgettable" initiative from the Department of Chemistry:the inaugural Visiting Faculty Research Partnership (VFRP), which wrapped recently with a symposium and poster session that celebrated visiting professors and their undergraduates from Fresno State, Rowan and Valdosta State universities.

The two-month summer program draws faculty from moderate to small research institutions that serve historically underrepresented groups. This inaugural year provided research and stipend funding to three visiting faculty who each brought two undergraduates with them.

Visiting faculty in Princeton Chemistrys two-month Visiting Faculty Research Partnership, at Frick Laboratory. From left: Qiao-Hong Chen, professor in the Department of Chemistry and Biochemistry at California State University, Fresno; Tolulope Salami, professor in the Department of Chemistry at Valdosta State University; Rashanique Quarels, assistant professor in the Department of Chemistry and Biochemistry at Rowan University; and Princeton Chemistry Department Chair Gregory Scholes, the William S. Tod Professor of Chemistry.

Photo by

C. Todd Reichart, Department of Chemistry

The visitors paired up with Princeton faculty and embedded in labs, group meetings and workshops to complete research collaborations.

I am thrilled to see the positive impact Princeton Chemistrys VFRP had for all participating faculty and students, said Shawn Maxam, associate provost for diversity and inclusion. The relationships and collaborations developed seem to be exceptional. We know that talent exists everywhere, and our pursuit of academic excellence requires a robust engagement with diverse groups of scientists and scholars.

My gratitude to the department for launching this program. I am excited by the future opportunities for science and collaboration catalyzed by VFRP, he said.

The three visiting professors were Qiao-Hong Chen, professor in the Department of Chemistry and Biochemistry at California State University, Fresno; Rashanique Quarels, assistant professor in the Department of Chemistry and Biochemistry at Rowan University; and Tolulope Salami, professor in the Department of Chemistry at Valdosta State University.

VFRP is part of department chair Greg Scholes goal to open Princeton Chemistry to non-traditional routes of collaboration.

What a great response we got for this program. It says a lot that we could make three top-quality appointments that spanned three different labs in our department, said Scholes, the William S. Tod Professor of Chemistry. We imagine that the experience will enhance the visiting students applications for graduate school or employment, and that we have seeded productive, long-term connections with them.

Chen and her two students partnered with Erik Sorensen, the Arthur Allan Patchett Professor in Organic Chemistry, and his research group. After two months, Chen declared the program an exciting, unforgettable summer of research. Its been a great chance for me, for my two students who came with me, and my entire group at Fresno State. We were all so happy to do this.

A first-generation college student herself, Chen chose two undergraduates to accompany her whom she felt would most benefit from the opportunity: Jasmine Hang and first-generation college student Khamyl Cooksey, both of whom traveled to the East Coast for the first time.

Coming here pushed me a little bit more towards doing a Ph.D., said Hang. Im actually a biology major, so chemistry wasnt ever anything I was going to touch other than the classes I need to take. But I really enjoyed the hands-on part of the lab. So now, Im thinking maybe I can do research on campus.

Tolulope Salami (center) and his undergraduates Jayden Thomas (left) and Jodeci Mitchell (right) from Valdosta State University atttend the Summer Symposium Poster Session at Frick Laboratory.

Photo by

C. Todd Reichart, Department of Chemistry

I have loved every moment of it, she added. Being able to work here and be a part of the whole environment where everyone is so research-driven, it just makes it so much more impactful.

Said Cooksey: The Sorensen Lab was very welcoming. We got to talk to the postdocs and graduate students and hear a lot about the paths theyve taken. Its definitely given me the opportunity to explore my options.

Jodeci Mitchell, who visited with Salami from Valdosta, embedded with the Bocarsly Lab, the research group of Professor Andrew Bocarsly. This program has given me access to more diverse experimentation and different equipment. Using that knowledge is definitely going to be useful to my career, no matter what I decide to do, she said. The hands-on activity in the lab is definitely beneficial in that aspect. Just getting used to the lab environment in general has been wonderful.

Salami said he feels its important to continue learning throughout ones professional career, and he found the opportunity to do that with the Bocarsly Lab.

The students too, theyve been encouraged that they can do this, he said. They had some trepidation about coming to Princeton, but when they got here, it was like, Hmmm, I actually can do this. Were all just chemists. I think it has done a lot to build their confidence.

Quarels and her two students from Rowan University partnered with Rob Knowles, a professor of chemistry, and his research group. Quarles noted that the Knowles Lab has a piece of equipment integral to her research a cryocooler, a refrigerator designed to reach cryogenic temperatures that is not available at Rowan. Just being able to utilize some of the resources here at Princeton was a big check for me.

She added that one of the students who accompanied her, Jonathan Santoro, was up until this point a chemical engineering major at Rowan. Following this summers fellowship, he plans to change his major to chemistry full time and continue on the path to graduate school.

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Inaugural program with Fresno State, Rowan and Valdosta State universities spurs unforgettable summer of research - Princeton University

Biochemistry Definition

Biochemistry is the study of the chemical reactions that take place inside organisms. It combines elements from both biology and chemistry. Biochemistry became a separate discipline in the early 20th Century. Biochemists study relatively large molecules like proteins, lipids, and carbohydrates, which are important in metabolism and other cellular activities; they also study molecules like enzymes and DNA.

Biochemistry research has been done for around the past 400 years, although the term biochemistry itself was only coined in 1903 by the German chemist Carl Neuberg. The study of biochemistry essentially began with the invention of the microscope in 1665 by Robert Hooke. He was the first person to observe cells under a microscope, but they were dead cells; later on in 1674, Anton van Leeuwenhoek saw live plant cells under a microscope. Now that scientists had seen cells for the first time, they were eager to study them and discover more about the processes that occurred inside them. In the 18th Century, the French scientist Antoine Lavoisier proposed a reaction mechanism for photosynthesis, which is the process by which plants make their own food out of carbon dioxide, water, and sunlight, releasing oxygen in the process. He also was the first person to investigate the process of cell respiration, the process of making the energy molecule adenosine triphosphate (ATP) in the mitochondria of the cell.

In the 19th Century, a prevailing belief was that protoplasm, the jelly-like inside of the cell, carried out all of the processes involved with breaking down food molecules. It was believed that the chemistry of living organisms was inherently different from that of non-living ones. In 1897, Eduard Buchner performed an experiment that would change this view. He prepared an extract from yeast that he called zymase. Although zymase did not contain any living yeast cells, it could still ferment glucose to produce carbon dioxide and ethanol. Following Buchners convention, enzymes began to be named for the reaction they carried out; for example, DNA polymerase polymerizes DNA. (Zymase was later found to be multiple enzymes.)

In the 20th Century, further advancements were made. Hans Krebs discovered the citric acid cycle (which would also become known as the Krebs cycle), a series of chemical reactions during cellular respiration where glucose and oxygen are converted to ATP, carbon dioxide, and water. Also, DNA became known as the genetic material of the cell and its structure was identified by James Watson and Francis Crick from previous research done by Rosalind Franklin. Presently, newer technology such as recombinant DNA, gene splicing, radioisotopic labelling, and electron microscopy are advancing scientific knowledge further than ever before.

Topics in biochemistry research include enzyme mechanisms and kinetics, the making of proteins from DNA, RNA, and amino acids through the processes of transcription and translation, and the metabolic processes of cells. Biochemistry is closely related to molecular biology, which is the study of biological molecules such as DNA, proteins, and other macromolecules. Molecular biology techniques are often used to study biochemistry, along with techniques from other fields like immunology and physics. Since all life can be broken down into small molecules and chemical reactions, biochemistry is a broad science that is used in studying all types of biology, from botany to molecular genetics to pharmacology. Chemical reactions in cells are emphasized, but specific research topics can vary widely. For example, biochemists may be interested in researching the chemical reactions that occur in the brain (thereby connecting biochemistry with neurochemistry), how cells divide and differentiate, cell communication, the chemical basis of genetic inheritance, or how diseases such as cancer spread.

This is an image of a biochemist working in a laboratory.

Biochemistry is a laboratory science. To work in the field of biochemistry, an individual must be interested in conducting research, and should obtain at least a bachelors degree. Many biochemists teach and are principal investigators of research laboratories at universities; these positions require PhDs. While most biochemists with PhDs conduct research, some are academic lecturers and solely teach at universities. However, these biochemists also had to do research throughout graduate school in order to complete their PhD thesis. Other biochemists are lab managers, which requires a masters degree. With a bachelors degree, one may become a scientific research technician. The more education an individual has, generally the more independence they will have in a lab. Technicians carry out bench work and help perform experiments that a principal investigator designs. A lab manager has more responsibilities than a technician and may do independent research projects under the guidance of a principal investigator. Aside from academia, biochemists also work in industry positions. They may work in government laboratories or for a variety of companies including agricultural, pharmaceutical, public health, or biotechnology companies. Others provide specific services such as toxicology or forensics.

In order to be a competent biochemist, one must be interested in biology or chemistry research and learn proper laboratory skills and safety procedures. It is also important to have an aptitude for mathematics and statistics, and be able to analyze the data generated from experiments. The ability to think outside the box and brainstorm new ideas is important for designing experiments. Biochemists must also keep up with the scientific literature by reading recent publications in scientific journals and attending conferences. Although it takes a lot of hard work, training, and study, biochemists are able to uncover new information about the chemistry of living things and contribute to advancing scientific knowledge.

Students interested in becoming biochemists need to take many science courses during their time as an undergraduate. General knowledge of both biology and chemistry is essential. Many schools offer biochemistry as a specific major. It is also possible to become a biochemist after obtaining a biology or chemistry bachelors degree, but one needs to make sure that they have a good background in the subject they are not majoring in; i.e., an undergraduate majoring in biology needs to take chemistry courses (this is usually a requirement of all undergraduate biology majors), and an undergraduate majoring in chemistry should also take biology courses. Of course, there are also specifically biochemistry courses that students should take. Additionally, it is important to be well versed in mathematics and physics.

As students advance in their undergraduate career, they will take more specific science courses based on their specific interests. For example, they could take classes in botany, molecular biology, biophysics, biomedical sciences, or structural biology (how molecules are organized into cells and tissues), depending on where their research interests lie.

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Biochemistry - Definition, Careers and Major | Biology Dictionary

How does a nose remember that its a nose? Or an eye remember that its an eye?

As scientists probe the question of how cells remember what kind of cells they are supposed to be, or their genetic lineage, its important to understand how cells express different genes without changing the DNA sequence itself.

But studying this subject is difficult: Researchers can purify the proteins that drive genetic expression, put them in a test tube and watch them bind. But doing so inside the nucleus of cells, their native environment, has been so far impossible.

Study: HP1 oligomerization compensates for low-affinity H3K9me recognition and provides a tunable mechanism for heterochromatin-specific localization (DOI: 10.1126/sciadv.abk0793)

Now, a team of researchers at three University of Michigan labs have been able to track how a protein binds to its chromatin substrate within a living cell by establishing a collaboration that combines state-of-the-art ultra high-resolution imaging, synthetic protein design and computational modeling. Their results are published in Science Advances.

The biological question that were asking is, How do cells actually remember past experiences? And how do these experiences also lead to cells establishing distinct identities, as it happens in the case of the human body where you have lineages of cells that form neurons, or blood cells, or brain cells, and all actually maintain their identities for many generations,' said lead author Kaushik Ragunathan, assistant professor of biological chemistry at the U-M Medical School.

An example I like to think about is that if you chop off your nose, you dont get a hand growing there, even though the genome in your nose and the genome in your hand are exactly the same.

Cells control how and which genes are expressed from a copy of the DNA sequence held within each cell, despite that sequence being the same across all cells in the body. One way they control expression is by changing how tightly the DNA is packaged within the nucleus using proteins called histones. Histones can be modified through the addition of small chemical tags that regulate how tightly the DNA is wound around them and thus whether the genes can be expressed.

Proteins that have the ability to read, write and erase these histone tags explore the DNA within the nucleus of the cell very rapidlyon the order of milliseconds, according to Ragunathan. Ultimately, all this epigenetic information needs to be inherited across generations, but the recognition of these tags is a complicated process that involves chromatin binding and proteins meeting and interacting with each other amidst the chaos of all other possible competing interactions within the cell.

Being able to understand each step of the processand therefore enabling control of how the epigenetic information is inheritedintrigued co-author Julie Biteen, professor of chemistry and biophysics.

Biteen uses single-molecule fluorescence imaging to track individual proteins inside cells. Her lab can see where these proteins are relative to the chromatin, and Ragunathans expertise is in the molecular mechanisms underpinning how histone modifications and histone-binding proteins interact. These two worlds needed to come together so that the biochemistry of what happens in a test tube outside of cells could be tested to figure out what happens inside of them.

The timing of this process is critically important to ensure that the right genes are silenced at the right place and at the right time, Biteen said. What hooked me on this project is that in vitroin a test tubeyou can purify two proteins, watch them bind and see how good that binding is, or what is the affinity for one another. That tells you what can happen in the cells, but not what does happen in the cells.

Biteen and Ragunathan worked with Peter Freddolino, associate professor of biological chemistry, and computational medicine and bioinformatics at the U-M Medical School, to combine computer modeling with their experimental results.

This is really where our collaboration becomes really powerful, Biteen said. On one hand, seeing molecules is very helpful and knowing how fast the molecules move helps a lot in terms of understanding what is possible inside the cell, but here we could take a leap forward by perturbing the system even in unnatural ways in order to understand what these different motions of molecules in the cell actually mean.

While epigenetic marks are tremendously important for maintaining different tissues in complex organisms like humans, they also play an important role in regulating genes of single-celled organisms such as yeast. The team focused on a type of HP1 protein in yeast cells called Swi6. This family of proteins binds to a specific type of histone modifications in the cell to enforce gene silencing. By integrating fluorescent labels with Swi6, Bitees lab watched Swi6 move inside the cells nucleus.

While Swi6 searches for the correct binding site on DNA, it moves quickly, Biteen said. When it finds its target, it slows down significantly. The movement of a protein within the cell is akin to gears in a car and things can move at different speeds based on whom proteins interact with.

From these spaghetti tracks that we get inside the cell, we then figure out how much time they are spending searching and how much of the time they are spending bound, Biteen said. The amount of time they spend not moving tells us about how strongly theyre interacting and their biochemical properties.

While Biteens lab can measure movements in the cell on the scale of tens of milliseconds, much of the biochemistry happening in the cell is happening even faster, she said. Freddolino took this experimental information and developed models to estimate the ability of the Swi6 proteins to jump between the binding states that were identified in experiments.

Freddolinos modeling took into account the experimental measurements and the possible biochemical properties, which includes how the Swi6 molecules interact in the cell. These interactions include molecules that freely float in the solution of the cell, molecules that have bound to DNA, and molecules that are holding hands with each other, he said.

My lab wanted to come up with a more fine-grained model that estimated what was the most likely set of molecular states of the proteins and their ability to jump between those states, that would then give rise to the imaging data that Biteens lab created, Freddolino said.

Having this numerical model allows us to do the computational experiments of what happens if the protein binding is twice as fast as we think. What if its 10 times as fast as we think? Or 10 times slower? Could that still give rise to the data? Very happily, in this case, we were able to show that the relevant processes were really being captured in the fluorescence microscopy.

After identifying the binding properties of natural Swi6, the researchers tested their findings by redesigning Swi6 from its components to see whether they could replicate some of its biochemical properties, Ragunathan said. This allowed the researchers to determine that the imaging and modeling conducted in the first part of the paper reflects how the protein was binding in its native environment.

Can we do what nature did over the course of millions of years and make a protein that in many ways has properties similar to that of Swi6 in cells? Ragunathan said. In vivo biochemistry, which is what weve decided to call this, was not something that was ever thought to be possible inside living cells, but we have shown this is entirely feasible by using imaging as a modality. We are using this project as a foundation in order to understand how these epigenetic states can be established and maintained across generations.

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U-M researchers track protein binding, build synthetic proteins to study gene expression - University of Michigan News