scholarly journals 21st century miniguide to fungal biotechnology

2019 ◽  
Vol 5 (1) ◽  
pp. 11-42
Author(s):  
Carmen Sánchez ◽  
David Moore ◽  
Geoff Robson ◽  
Tony Trinci
Keyword(s):  
Genetic Structure ◽  
Cell Biology ◽  
Gene Editing ◽  
Genomic Variation ◽  
Fungal Cell ◽  
Biotechnological Potential ◽  
Plastic Wastes ◽  
Fungal Genetic ◽  
Fungal Genomes ◽  
New Strategies

Realising the biotechnological potential of fungi requires full appreciation of the molecular biology and genetics of this kingdom. We review recent advances in our understanding of fungal genetic structure as it might influence biotechnology; including introns, alternative splicing of primary transcripts, transposons (transposable elements, or TEs), heterokaryosis, ploidy and genomic variation, sequencing, annotation and comparison of fungal genomes, and gene editing. We end by indicating under-researched, but unique, aspects of fungal cell biology that offer opportunities for developing new strategies to manage the activities of fungi to our benefit. As a closing example, we discuss the potential of bioengineering fungi specifically for bioremediation of plastic wastes.

scholarly journals Genomic variation in the American pika: signatures of geographic isolation and implications for conservation

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Kelly B. Klingler ◽  
Joshua P. Jahner ◽  
Thomas L. Parchman ◽  
Chris Ray ◽  
Mary M. Peacock
Keyword(s):  
Genetic Variation ◽  
Genetic Structure ◽  
Sierra Nevada ◽  
Spatial Genetic Structure ◽  
Spatial Scales ◽  
Thermal Sensitivity ◽  
Genomic Variation ◽  
Genome Wide ◽  
A Genome ◽  
American Pika

Abstract Background Distributional responses by alpine taxa to repeated, glacial-interglacial cycles throughout the last two million years have significantly influenced the spatial genetic structure of populations. These effects have been exacerbated for the American pika (Ochotona princeps), a small alpine lagomorph constrained by thermal sensitivity and a limited dispersal capacity. As a species of conservation concern, long-term lack of gene flow has important consequences for landscape genetic structure and levels of diversity within populations. Here, we use reduced representation sequencing (ddRADseq) to provide a genome-wide perspective on patterns of genetic variation across pika populations representing distinct subspecies. To investigate how landscape and environmental features shape genetic variation, we collected genetic samples from distinct geographic regions as well as across finer spatial scales in two geographically proximate mountain ranges of eastern Nevada. Results Our genome-wide analyses corroborate range-wide, mitochondrial subspecific designations and reveal pronounced fine-scale population structure between the Ruby Mountains and East Humboldt Range of eastern Nevada. Populations in Nevada were characterized by low genetic diversity (π = 0.0006–0.0009; θW = 0.0005–0.0007) relative to populations in California (π = 0.0014–0.0019; θW = 0.0011–0.0017) and the Rocky Mountains (π = 0.0025–0.0027; θW = 0.0021–0.0024), indicating substantial genetic drift in these isolated populations. Tajima’s D was positive for all sites (D = 0.240–0.811), consistent with recent contraction in population sizes range-wide. Conclusions Substantial influences of geography, elevation and climate variables on genetic differentiation were also detected and may interact with the regional effects of anthropogenic climate change to force the loss of unique genetic lineages through continued population extirpations in the Great Basin and Sierra Nevada.

Manipulating dendritic cell biology for the active immunotherapy of cancer

Blood ◽  
2004 ◽  
Vol 104 (8) ◽  
pp. 2235-2246 ◽  
Author(s):  
David W. O'Neill ◽  
Sylvia Adams ◽  
Nina Bhardwaj
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Cell Biology ◽  
Active Immunotherapy ◽  
Transplantation Tolerance ◽  
Chronic Infections ◽  
Immunotherapy Of Cancer ◽  
Antigen Presenting ◽  
And Control ◽  
New Strategies

Abstract Dendritic cells (DCs) are specialized antigen-presenting cells (APCs) that have an unequaled capacity to initiate primary immune responses, including tolerogenic responses. Because of the importance of DCs in the induction and control of immunity, an understanding of their biology is central to the development of potent immunotherapies for cancer, chronic infections, autoimmune disease, and induction of transplantation tolerance. This review discusses recent advances in DC research and the application of this knowledge toward new strategies for the clinical manipulation of DCs for cancer immunotherapy.

scholarly journals Genomic variation in the American pika: signatures of geographic isolation and implications for conservation

2020 ◽  
Author(s):  
Kelly Brie Klingler ◽  
Joshua P Jahner ◽  
Thomas L Parchman ◽  
Chris Ray ◽  
Mary Peacock
Keyword(s):  
Genetic Variation ◽  
Genetic Structure ◽  
Sierra Nevada ◽  
Spatial Genetic Structure ◽  
Spatial Scales ◽  
Thermal Sensitivity ◽  
Genomic Variation ◽  
Genome Wide ◽  
A Genome ◽  
American Pika

Abstract Background: Distributional responses by alpine taxa to repeated, glacial-interglacial cycles throughout the last two million years have significantly influenced the spatial genetic structure of populations. These effects have been exacerbated for the American pika (Ochotona princeps), a small alpine lagomorph constrained by thermal sensitivity and a limited dispersal capacity. As a species of conservation concern, long-term lack of gene flow has important consequences for landscape genetic structure and levels of diversity within populations. Here, we use reduced representation sequencing (ddRADseq) to provide a genome-wide perspective on patterns of genetic variation across pika populations representing distinct subspecies. To investigate how landscape and environmental features shape genetic variation, we collected genetic samples from distinct geographic regions as well as across finer spatial scales in two geographically proximate mountain ranges of eastern Nevada. Results: Our genome-wide analyses corroborate range-wide, mitochondrial subspecific designations and reveal pronounced fine-scale population structure between the Ruby Mountains and East Humboldt Range of eastern Nevada. Populations in Nevada were characterized by low genetic diversity (𝜋=0.0006–0.0009; 𝜃W=0.0005–0.0007) relative to populations in California (𝜋=0.0014–0.0019; 𝜃W=0.0011–0.0017) and the Rocky Mountains (𝜋=0.0025–0.0027; 𝜃W=0.0021–0.0024), indicating substantial genetic drift in these isolated populations. Tajima’s D was positive for all sites (D=0.240-0.811), consistent with recent contraction in population sizes range-wide. Conclusions: Substantial influences of geography, elevation and climate variables on genetic differentiation were also detected and may interact with the regional effects of anthropogenic climate change to force the loss of unique genetic lineages through continued population extirpations in the Great Basin and Sierra Nevada.

scholarly journals Naive and in vitro-activated primary mouse CD8+ T cells retain in vivo immune responsiveness after electroporation-based CRISPR/Cas9 genetic engineering

2021 ◽  
Author(s):  
Petra Pfenninger ◽  
Laura Yerly ◽  
Jun Abe
Keyword(s):  
T Cells ◽  
Genetic Engineering ◽  
Cell Biology ◽  
Gene Editing ◽  
Decay Rates ◽  
Immune Responsiveness ◽  
Primary Mouse ◽  
Time Required

CRISPR/Cas9 technology has revolutionized genetic engineering of primary cells. Although its use is gaining momentum in studies on CD8+ T cell biology, it remains elusive to what extent CRISPR/Cas9 affects in vivo function of CD8+ T cells. Here, we optimized nucleofection-based CRISPR/Cas9 genetic engineering of naive and in vitro-activated primary mouse CD8+ T cells and tested their in vivo immune responses. Nucleofection of naive CD8+ T cells preserved their in vivo antiviral immune responsiveness to an extent that is indistinguishable from non-nucleofected cells, whereas in vitro activation of CD8+ T cells prior to nucleofection led to slightly impaired expansion/survival. Of note, different target proteins displayed distinct decay rates after gene editing. This is in stark contrast to a comparable period of time required to complete gene inactivation. Thus, for optimal experimental design, it is crucial to determine the kinetics of the loss of target gene product to adapt incubation period after gene editing. In sum, nucleofection-based CRISPR/Cas9 genome editing achieves efficient and rapid generation of mutant CD8+ T cells without imposing detrimental constraints on their in vivo functions.

scholarly journals The Mechanobiology of the Actin Cytoskeleton in Stem Cells during Differentiation and Interaction with Biomaterials

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
X. Ambriz ◽  
P. de Lanerolle ◽  
J. R. Ambrosio
Keyword(s):  
Mechanical Properties ◽  
Stem Cells ◽  
Actin Cytoskeleton ◽  
Cell Biology ◽  
Culture Conditions ◽  
Cellular Biology ◽  
Stem Cell Biology ◽  
Cell Culture Conditions ◽  
New Strategies

An understanding of the cytoskeleton’s importance in stem cells is essential for their manipulation and further clinical application. The cytoskeleton is crucial in stem cell biology and depends on physical and chemicals signals to define its structure. Additionally, cell culture conditions will be important in the proper maintenance of stemness, lineage commitment, and differentiation. This review focuses on the following areas: the role of the actin cytoskeleton of stem cells during differentiation, the significance of cellular morphology, signaling pathways involved in cytoskeletal rearrangement in stem cells, and the mechanobiology and mechanotransduction processes implicated in the interactions of stem cells with different surfaces of biomaterials, such as nanotopography, which is a physical cue influencing the differentiation of stem cells. Also, cancer stem cells are included since it is necessary to understand the role of their mechanical properties to develop new strategies to treat cancer. In this context, to study the stem cells requires integrated disciplines, including molecular and cellular biology, chemistry, physics, and immunology, as well as mechanobiology. Finally, since one of the purposes of studying stem cells is for their application in regenerative medicine, the deepest understanding is necessary in order to establish safety protocols and effective cell-based therapies.

scholarly journals Molecular Mechanisms and Determinants of Innovative Correction Approaches in Coagulation Factor Deficiencies

2019 ◽  
Vol 20 (12) ◽  
pp. 3036 ◽  
Author(s):  
Dario Balestra ◽  
Alessio Branchini
Keyword(s):  
Gene Editing ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Coagulation Factor ◽  
Coagulation Factors ◽  
Therapeutic Approaches ◽  
Protein Levels ◽  
Functional Factors ◽  
New Strategies ◽  
I Gene

Molecular strategies tailored to promote/correct the expression and/or processing of defective coagulation factors would represent innovative therapeutic approaches beyond standard substitutive therapy. Here, we focus on the molecular mechanisms and determinants underlying innovative approaches acting at DNA, mRNA and protein levels in inherited coagulation factor deficiencies, and in particular on: (i) gene editing approaches, which have permitted intervention at the DNA level through the specific recognition, cleavage, repair/correction or activation of target sequences, even in mutated gene contexts; (ii) the rescue of altered pre-mRNA processing through the engineering of key spliceosome components able to promote correct exon recognition and, in turn, the synthesis and secretion of functional factors, as well as the effects on the splicing of missense changes affecting exonic splicing elements; this section includes antisense oligonucleotide- or siRNA-mediated approaches to down-regulate target genes; (iii) the rescue of protein synthesis/function through the induction of ribosome readthrough targeting nonsense variants or the correction of folding defects caused by amino acid substitutions. Overall, these approaches have shown the ability to rescue the expression and/or function of potentially therapeutic levels of coagulation factors in different disease models, thus supporting further studies in the future aimed at evaluating the clinical translatability of these new strategies.

scholarly journals Fungal Biology and Agriculture: Revisiting the Field

2003 ◽  
Vol 16 (10) ◽  
pp. 859-866 ◽  
Author(s):  
O. Yarden ◽  
D. J. Ebbole ◽  
S. Freeman ◽  
R. J. Rodriguez ◽  
M. B. Dickman
Keyword(s):  
Dna Sequences ◽  
Cell Biology ◽  
Plant Disease ◽  
Plant Protection ◽  
Basic Research ◽  
Data Sets ◽  
Data Organization ◽  
Fungal Cell ◽  
Fungal Biology ◽  
Plant Disease Management

Plant pathology has made significant progress over the years, a process that involved overcoming a variety of conceptual and technological hurdles. Descriptive mycology and the advent of chemical plant-disease management have been followed by biochemical and physiological studies of fungi and their hosts. The later establishment of biochemical genetics along with the introduction of DNA-mediated transformation have set the stage for dissection of gene function and advances in our understanding of fungal cell biology and plant-fungus interactions. Currently, with the advent of high-throughput technologies, we have the capacity to acquire vast data sets that have direct relevance to the numerous subdisciplines within fungal biology and pathology. These data provide unique opportunities for basic research and for engineering solutions to important agricultural problems. However, we also are faced with the challenge of data organization and mining to analyze the relationships between fungal and plant genomes and to elucidate the physiological function of pertinent DNA sequences. We present our perspective of fungal biology and agriculture, including administrative and political challenges to plant protection research.

scholarly journals Mapping human cell phenotypes to genotypes with single-cell genomics

Science ◽  
2019 ◽  
Vol 365 (6460) ◽  
pp. 1401-1405 ◽  
Author(s):  
J. Gray Camp ◽  
Randall Platt ◽  
Barbara Treutlein
Keyword(s):  
Single Cell ◽  
Human Cell ◽  
Cell Biology ◽  
Life Histories ◽  
Gene Editing ◽  
Cell Types ◽  
Single Cell Genomics ◽  
Cumulative Activity ◽  
Cellular Phenotypes ◽  
Cell Phenotypes

The cumulative activity of all of the body’s cells, with their myriad interactions, life histories, and environmental experiences, gives rise to a condition that is distinctly human and specific to each individual. It is an enduring goal to catalog our human cell types, to understand how they develop, how they vary between individuals, and how they fail in disease. Single-cell genomics has revolutionized this endeavor because sequencing-based methods provide a means to quantitatively annotate cell states on the basis of high-information content and high-throughput measurements. Together with advances in stem cell biology and gene editing, we are in the midst of a fascinating journey to understand the cellular phenotypes that compose human bodies and how the human genome is used to build and maintain each cell. Here, we will review recent advances into how single-cell genomics is being used to develop personalized phenotyping strategies that cross subcellular, cellular, and tissue scales to link our genome to our cumulative cellular phenotypes.

scholarly journals A Histoplasma capsulatum lipid metabolic map identifies antifungal targets and virulence factors

2020 ◽  
Author(s):  
Daniel Zamith-Miranda ◽  
Heino M. Heyman ◽  
Meagan C. Burnet ◽  
Sneha P. Couvillion ◽  
Xueyun Zheng ◽  
...  
Keyword(s):  
Immune Response ◽  
Drug Development ◽  
Cell Biology ◽  
Histoplasma Capsulatum ◽  
Platelet Activating Factor ◽  
Interleukin 10 ◽  
Antifungal Drugs ◽  
New Drugs ◽  
Fungal Cell ◽  
Factor Α

AbstractLipids play a fundamental role in fungal cell biology, being components of the cell membrane as well as targets of antifungal drugs. A deeper knowledge of lipid metabolism is key for developing new drugs and a better understanding of fungal pathogenesis. Here we built a comprehensive map of the Histoplasma capsulatum lipid metabolic pathway by integrating proteomic and lipidomic analyses. The map led to the identification of both the fatty acid desaturation and the sphingolipid biosynthesis pathways as targets for drug development. We also found that H. capsulatum produces analogs of platelet-activating factor, a potent regulator of the human immune response. The H. capsulatum platelet-activating factor analogs induced platelet aggregation and stimulated the production of the cytokines interleukin-10 and tumor necrosis factor-α by J774 macrophages. Overall, this lipid metabolic map revealed pathways that can be targeted for drug development, in addition to identifying a regulator of the host immune response.

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