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  • A comprehensive database for the study of protein aggregation

    A comprehensive database for the study of protein aggregation
    8th November 2023

    Credit: Autonomous University of Barcelona

    Researchers at the IBB-UAB have developed the most comprehensive database available to date to help understand the basis of protein aggregation, a phenomenon associated with aging and several pathologies. The new resource, A3D-MOBD, brings together the proteomes of 12 of the most studied model organisms, which cover distant biological clades, and contains more than half a million predictions of protein regions with a propensity to form aggregates. The A3D-MOBD was developed by the Protein Folding and Computational Diseases Group at the Institut de Biotecnologia i de Biomedicina of the Universitat Autònoma de Barcelona (IBB-UAB), which is directed by Biochemistry and Molecular Biology Professor Salvador Ventura. In collaboration with scientists from the University of Warsaw, the study was recently published in the journal Nucleic Acids Research. It provides pre-calculated aggregation propensity analyses and tools for the study of this phenomenon on a proteomic scale as well as evolutionary comparison between different species.

    The new resource builds on the method that the same research group designed in 2015, Aggrescan 3D, but significantly expands the obtainable data. In total, it contains more than 500,000 structural predictions for more than 160,000 proteins from 12 highly characterized model organisms widely used in biology, biotechnology and biomedicine research.

    It includes the herbaceous plant Arabidopsis thaliana,  nematode worm Caenorhabditis elegans, zebrafish Danio rerio, enteric bacterium Escherichia coli, minimal genome bacteria Mycoplasma genitalium, mouse Mus musculus, fusion and fission yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe, human Homo sapiens, rat Rattus norvegicus, fruit fly Drosophila melanogaster and  COVID-19 causative virus SARS-CoV-2.

     

    By Autonomous University of Barcelona

    Article can be accessed on: phys.org

  • Study shows the microbiome of fruit and vegetables positively influences diversity in the gut

    Study shows the microbiome of fruit and vegetables positively influences diversity in the gut
    27th October 2023

    Overview of the bioinformatic workflow for the recovery of metagenome-assembled genomes (MAGs) from fruits and vegetables and the detection of their presence in the gut. Credit: DOI: 10.1080/19490976.2023.2258565

    It is known that an important part of the maternal microbiome is transferred to the baby at birth, and the same happens during the breastfeeding period via breast milk. Further sources were yet to be discovered. However, a team led by Wisnu Adi Wicaksono and Gabriele Berg from the Institute of Environmental Biotechnology at Graz University of Technology (TU Graz) has now succeeded in proving that plant microorganisms from fruit and vegetables contribute to the human microbiome. They report this in a study published in the journal Gut Microbes. The authors were able to demonstrate that the frequency of fruit and vegetable consumption and the variety of plants consumed influences the amount of fruit- and vegetable-associated bacteria in the human gut. Early childhood in particular represents a window of opportunity for colonization with plant-associated bacteria. It was also demonstrated that the microorganisms of plant origin have probiotic and health-promoting properties. A microbiome is the totality of all microorganisms that colonize a macroorganism (human, animal, plant) or a part of it, for example the intestine or a fruit. While the individual microbiomes are becoming better understood, little is known about their connections.

    “The proof that microorganisms from fruits and vegetables can colonize the human gut has now been established for the first time,” explains first author Wisnu Adi Wicaksono.

     

    By Falko Schoklitsch, Graz University of Technology

    Article can be accessed on: MedicalXpress

  • Scientists use custom genome assembly and editing method to improve sheepgrass

    Scientists use custom genome assembly and editing method to improve sheepgrass
    27th October 2023

    Morphological view and genomic profile of forage Sheepgrass. Credit: IGDB

    A research team led by Dr. Cao Xiaofeng at the Institute of Genetics and Developmental Biology of the Chinese Academy of Sciences has improved biomass-related traits in sheepgrass using its own custom genome editing system while increasing understanding of sheepgrass genomics. The team’s genome assembly and innovative gene editing system, characterized by the fusion of big data and biotechnology, reveals the potential for intelligent and rapid genomic breeding of sheepgrass. The study was published in PNAS on Oct. 24.

    Leymus chinensis (sheepgrass), a member of the Triticeae family, is a prominent grass species throughout the Eurasian steppe. This species, which is known for its robust rhizomes, has impressive attributes such as frost tolerance, drought tolerance, salt tolerance, and good soil stabilization capacity, etc.

    Sheepgrass is widely recognized as a high quality forage that provides both ecological and economic benefits due to its exceptional nutritional value and palatability. However, due to the sheepgrass genome’s large size and high heterozygosity, studying it and elucidating its outstanding properties is challenging.

    In this study, the researchers selected L. chinensis Lc6-5, a type of sheepgrass from the grasslands of Northeast China with strong rhizomes. They performed genome assembly using cutting-edge sequencing and assembly techniques. The assembled genome size was approximately eight Gb, with a contig N50 of more than 300 Mb and repetitive sequences accounting for 87.76% of the genome.

     

    By Zhang Nannan, Chinese Academy of Sciences

    Article can be accessed on: phys.org
  • Regenerative cell therapy for epilepsy

    Regenerative cell therapy for epilepsy
    16th October 2023

    Credit: Cell Stem Cell (2023). DOI: 10.1016/j.stem.2023.08.013

    Together with colleagues, veterinarian and neuroscientist Sonja Bröer has researched how regenerative cell therapies can contribute to curing or alleviating epilepsy. The work was carried out at biotechnology start-up Neurona Therapeutics, Inc. in San Francisco, where Bröer led a team in preclinical research, before she moved to Freie Universität Berlin. The company is developing a cell therapy (NRTX-1001) for treatment-resistant epilepsy and has now published the results from preclinical studies in Cell Stem Cell. Based on these data, the cell therapy is now being evaluated in human patients as part of an ongoing phase 1/2 clinical trial. On October 6, 2023, Bröer will present both the preclinical and the first clinical data at the Einstein Center for Neurosciences’ Berlin Neuroscience Meeting. Approximately 50 million people worldwide suffer from epilepsy; in about one-third of patients, epileptic seizures do not respond to drug treatment, reducing patients’ quality of life as well as their life expectancy. Epilepsy occurs when excessive electrical discharges occur in nerve cells of the brain. The neurotransmitter gamma-aminobutyric acid (GABA) can block this overexcitation. However, the nerve cells that secrete this neurotransmitter can degenerate in patients with epilepsy, creating an imbalance between inhibition and excitation in the brain that is thought to pave the way for epileptic seizure activity. In their recent publication in Cell Stem Cell, Bröer and her colleagues report on the transplantation of inhibitory GABA-secreting neurons that can potentially restore the balance in the brain and suppress epileptic seizures.

    By Japhet Johnstone, Free University of Berlin

    Article can be accessed on: MedicalXpress

  • Researchers develop new open-source method to improve decoding of single-cell data

    Researchers develop new open-source method to improve decoding of single-cell data
    16th October 2023

    Credit: Nature Biotechnology (2023). DOI: 10.1038/s41587-023-01940-3

    Researchers at Memorial Sloan Kettering Cancer Center (MSK) have developed a new open-source computational method, dubbed Spectra, which improves the analysis of single-cell transcriptomic data. By guiding data analysis in a unique way, Spectra can offer new insights into the complex interplay between cells-like the interactions between cancer cells and immune cells, which are critical to improving immunotherapy treatments. The team’s approach and findings were recently published in Nature Biotechnology. Spectra, the researchers note, can cut through technical “noise” to identify functionally relevant gene expression programs, including those that are novel or highly specific to a particular biological context. The algorithm is well suited to study data from large patient cohorts and to suss out clinically meaningful patient characteristics, the MSK team writes in a research briefing that accompanies the study, adding that Spectra is ideal for identifying biomarkers and drug targets in the burgeoning field of immuno-oncology. Additionally, the MSK team has made Spectra freely available to researchers around the world.

    “I’m trained as a computer scientist,” says study senior author Dana Pe’er, Ph.D., who chairs the Computational and Systems Biology Program at MSK’s Sloan Kettering Institute. “Every single tool I build, I strive to make robust so it can be used in many contexts, not just one. I also try and make them as accessible as possible.”

    By Ian Demsky, Memorial Sloan Kettering Cancer Center

    Article can be accessed on: MedicalXpress

     

  • Gates Foundation funding $40 million effort to help develop mRNA vaccines in Africa in coming years

    Gates Foundation funding $40 million effort to help develop mRNA vaccines in Africa in coming years
    10th October 2023

    Bill Gates speaks to The Associated Press during a visit of the Institut Pasteur in dakar, Senegal, Sunday, Oct. 8, 2023. Credit: AP Photo

    A $40 million investment will help several African manufacturers produce new messenger RNA vaccines on the continent where people were last in line to receive jabs during the COVID-19 pandemic, the Bill & Melinda Gates Foundation announced Monday. While it could still take at least three more years before any of the vaccines are approved and on the market, the foundation said that its mRNA investment marks an important step forward in improving vaccine equity.

    “Whether it’s for local diseases in Africa like Rift Valley (fever) or for global diseases like TB, mRNA looks like a very promising approach,” Bill Gates told The Associated Press on Sunday after visiting one of the facilities involved, the Institut Pasteur in Dakar, Senegal. “And so it allows us to bring in lots of African capabilities to work on these vaccines, and then this can be scaled up. The announcement comes as the foundation opens its annual three-day Grand Challenges event, which brings together scientists and public health researchers from around the world.

    Institut Pasteur, along with the South Africa-based company Biovac, will be using an mRNA research and manufacturing platform that was developed by Quantoom Biosciences in Belgium. The two Africa-based vaccine manufacturers are receiving $5 million each in funding from the foundation, while another $10 million is earmarked for other companies that have not yet been named. The remaining $20 million is going to Quantoom “to further advance the technology and lower costs.”

    By Krista Larson

    Article can be accessed on: MedicalXpress

  • Split gene-editing tool offers greater precision

    Split gene-editing tool offers greater precision
    25th September 2023

    Chemically inducible split ABE (sABE) with tightly regulated deaminase activity. a Schematic of the EYFP fluorescence. An A-to-G conversion on the highlighted adenine on the antisense strand of the dysfunctional EYFP* gene can restore the expression of functional EYFP protein. b Schematic of the sABE. In the absence of rapamycin (Left), two parts of the TadA-8e: TadA-8eN and TadA-8ec, remain inactive. In the presence of rapamycin (Right), the rapamycin-FKBP3 complex binds to FRB, bringing the TadA-8eN and TadA-8ec to spatial proximity to form an active ABE unit. nCas9: Streptococcus pyogenes Cas9 (D10A) nickase; FKBP: FK506 binding proteins; FRB: FKBP-rapamycin binding domains. c EYFP* reporter assay in HEK293T cells. Cells are co-transfected with five plasmids, using EBFP as a transfection control. Representative FACS data show the EYFP* activation by sABE in the presence of rapamycin. d Crystal structure of the TadA-8e deaminase domain of ABE8e (PDB: 6VPC38). Highlighted loop-25 and loop-74 regions indicate where the TadA-8e is split into two parts for the sABE v1 and v2, respectively. e Engineering steps to increase the rapamycin-induced deaminase activity and to decrease the non-induced background. f Diagram of the sABE v3.22 constructs. pCMV: cytomegalovirus

    To make a gene-editing tool more precise and easier to control, Rice University engineers split it into two pieces that only come back together when a third small molecule is added. Researchers in the lab of chemical and biomolecular engineer Xue Sherry Gao created a CRISPR-based gene editor.

    By Silvia Cernea Clark, Rice University

    Article can be accessed on: phys.org

  • Novel approach to engineered cells may enable molecular medical imaging

    Novel approach to engineered cells may enable molecular medical imaging
    25th September 2023

    Credit:DOI: 10.1002/btm2.10584

    A tiny molecular structure that looks like a bubble may be able to significantly improve medical imaging, according to a Penn State research team. Called gas vesicles (GVs), these structures are naturally produced by certain microorganisms and are responsible for controlling the microorganism’s buoyancy in water. Researchers can genetically engineer human cells to produce these gas vesicles, resulting in an ultrasound contrast medium capable of revealing deep tissue structures at the resolution of a single cell. The problem is that the process to engineer such cells is costly and arduous. To make the process easier, Lance Lian, associate professor of biomedical engineering and of biology at Penn State, led a team in developing a more efficient approach. They published their work in Bioengineering and Translational Medicine.

    “The great thing about our approach is that it doesn’t require the tedious and time-consuming single-cell cloning and sorting methods,” said Lian, co-corresponding author on the paper. “Instead, we can work with a mixture of cells and still get strong and reliable ultrasound contrast.” In the context of this research, “single-cell cloning” refers to a labor-intensive process of isolating and cultivating individual cells that have undergone specific genetic modifications, such as incorporating the desired genes to produce GVs. Researchers typically do this to ensure that they are working with a population of cells that have uniform genetic characteristics.

    By Joslyn Neiderer, Pennsylvania State University

    Article can be accessed on: phys.org

  • Researchers create new spatial omics method

    Researchers create new spatial omics method
    8th September 2023

    Ion distribution images of (a) Penk(197-208) (SPQLEDEAKELQ, m/z 1386.67) and (c) Alpha-neoendorphin(2-10) (GGFLRKYPK, m/z 1065.62). Spatial gene expression of (b) Penk and (d) Tac1. Credit: Nature Biotechnology (2023). DOI: 10.1038/s41587-023-01937-y.

    Researchers at Uppsala University, Stockholm University and KTH Royal Institute of Technology have managed to create a new spatial omics method. By combining two complex techniques that are usually used separately mass spectrometry imaging (MSI) and spatially resolved transcriptomics (SRT) they have taken an important step in research on biological tissues. The study is published in the journal Nature Biotechnology.

    “Our method can visualize both low-molecular metabolites, such as signaling molecules in the brain, and RNA transcripts in the same biological tissue section without compromising on the quality or precision of results. The findings of this study have the potential to significantly advance the field of spatial biology and pathological research,” says Per Andrén, Professor of Mass Spectrometry Imaging at Uppsala University and SciLifeLab and one of the authors of the study.

    The method, successfully demonstrated using tissue sections from both mice and human brains, targeted signaling molecules and their role in Parkinson’s disease. By analyzing the complex molecular profiles in a single tissue section, researchers can obtain a deeper understanding of Parkinson’s disease and other complex illnesses.

    One important aspect of the method is its capability to visualize molecules and their distribution in the tissue while simultaneously analyzing gene activity. This methodology enables researchers to explore the connection between gene expression and molecular activity at a higher level.

    By Elin Bäckström, The Swedish Research Council

    Article can be accessed on: phys.org

  • Researchers develop a new reagent and method to create DNA and RNA polymer biohybrids

    Researchers develop a new reagent and method to create DNA and RNA polymer biohybrids
    5th September 2023

    Credit: Chem (2023). DOI: 10.1016/j.chempr.2023.07.013

    Researchers in Carnegie Mellon University’s Department of Chemistry have developed a reagent that opens new possibilities for creating DNA and RNA-based materials that could be used in ultra-stable and smart sensors for biomedical applications. The work was published on Aug. 22 in the journal Chem. “It’s a very emergent technology and pushing the field,” said Subha R. Das, associate professor of chemistry, who co-advises chemistry doctoral student Jaepil Jeong. Both Das and Jeong are members of Carnegie Mellon’s Center for Nucleic Acids Science and Technology, an interdisciplinary community of Carnegie Mellon and University of Pittsburgh scientists and engineers unified by interests in the chemistry, biology, and physics of DNA, RNA, and peptide nucleic acid. “Essentially, we now have access to a whole new class of biomaterials based on both nucleic acids and synthetic polymers.” Medical treatments using biopolymers are typically developed using proteins, Das said. But potential applications for DNA and RNA polymer biohybrids could include self-delivering genes and mRNA, ultra-stable and smart sensors, or therapeutics and gels for transplants and wound healing. Polymers developed using this method could potentially be used to create sequence-selective filters or membranes for biotechnology applications. The reagent, Serinolic ATRP initiator-modified phosphoramidite (SBiB), was developed by Jeong. The SBiB reagent enables researchers to incorporate multiple initiators anywhere in a DNA or RNA sequence during solid-phase synthesis. Previously it was only feasible to incorporate a single polymer chain initiator just at the end of a DNA strand.

    By Heidi Opdyke, Carnegie Mellon University

    Article can be accessed on: phys.org