NŠ
N. Šoštarić
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The SARS-CoV-2 nucleocapsid protein, or N-protein, is a structural protein that plays an important role in the SARS-CoV-2 life cycle. The N-protein takes part in the regulation of viral RNA replication and drives highly specific packaging of full-length genomic RNA prior to virion formation. One regulatory mechanism that is proposed to drive the switch between these two operating modes is the phosphorylation state of the N-protein. Here, we assess the dynamic behavior of non-phosphorylated and phosphorylated versions of the N-protein homodimer through atomistic molecular dynamics simulations. We show that the introduction of phosphorylation yields a more dynamic protein structure and decreases the binding affinity between the N-protein and RNA. Furthermore, we find that secondary structure is essential for the preferential binding of particular RNA elements from the 5′ UTR of the viral genome to the N-terminal domain of the N-protein. Altogether, we provide detailed molecular insights into N-protein dynamics, N-protein:RNA interactions, and phosphorylation. Our results corroborate the hypothesis that phosphorylation of the N-protein serves as a regulatory mechanism that determines N-protein function.
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The SARS-CoV-2 nucleocapsid protein, or N-protein, is a structural protein that plays an important role in the SARS-CoV-2 life cycle. The N-protein takes part in the regulation of viral RNA replication and drives highly specific packaging of full-length genomic RNA prior to virion formation. One regulatory mechanism that is proposed to drive the switch between these two operating modes is the phosphorylation state of the N-protein. Here, we assess the dynamic behavior of non-phosphorylated and phosphorylated versions of the N-protein homodimer through atomistic molecular dynamics simulations. We show that the introduction of phosphorylation yields a more dynamic protein structure and decreases the binding affinity between the N-protein and RNA. Furthermore, we find that secondary structure is essential for the preferential binding of particular RNA elements from the 5′ UTR of the viral genome to the N-terminal domain of the N-protein. Altogether, we provide detailed molecular insights into N-protein dynamics, N-protein:RNA interactions, and phosphorylation. Our results corroborate the hypothesis that phosphorylation of the N-protein serves as a regulatory mechanism that determines N-protein function.
This introductory programming book offers a hands-on approach to learning Python, designed specifically for students of natural sciences who wish to enter the world of coding. Covering fundamental programming concepts - from variables and data types to functions and loops - the book presents examples and exercises rooted in applications across biology, physics, and mathematics. In addition to Python fundamentals, readers also build good practices of programming and working with computers, such as using the terminal, navigating an integrated development environment, tracking changes with Git, and writing pseudocode. Moreover, the book addresses how to usage generative AI tools effectively when learning the basics of programming. Through hands-on learning, each chapter builds both confidence and competence, guiding students from simple scripts to more complex code. By the end of the book, students will not only understand Python’s core principles but also have the skills and tools to tackle real coding challenges within their scientific disciplines in the age of AI.
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This introductory programming book offers a hands-on approach to learning Python, designed specifically for students of natural sciences who wish to enter the world of coding. Covering fundamental programming concepts - from variables and data types to functions and loops - the book presents examples and exercises rooted in applications across biology, physics, and mathematics. In addition to Python fundamentals, readers also build good practices of programming and working with computers, such as using the terminal, navigating an integrated development environment, tracking changes with Git, and writing pseudocode. Moreover, the book addresses how to usage generative AI tools effectively when learning the basics of programming. Through hands-on learning, each chapter builds both confidence and competence, guiding students from simple scripts to more complex code. By the end of the book, students will not only understand Python’s core principles but also have the skills and tools to tackle real coding challenges within their scientific disciplines in the age of AI.
Journal article
(2025)
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M. Valeria Lattanzio, Nikolina Šoštarić, Nandhini Kanagasabesan, Branka Popović, Antonia Bradarić, Leyma Wardak, Aurélie Guislain, Philipp Savakis, Monika C. Wolkers
T cells are critical effector cells counteracting infections and malignancies. To achieve this, they produce pro-inflammatory cytokines, including IFN-γ and TNF. Cytokine production is a tightly regulated process, but the relative contribution of transcriptional and post-transcriptional regulation to mRNA expression remains unknown. We optimized single-molecule FISH for primary human T cells (T-cell smFISH) to simultaneously quantify nascent RNA, levels of mature mRNA, and its localization with single-cell resolution. T-cell smFISH uncovered heterogeneous cytokine mRNA levels, with high cytokine producers displaying biallelic IFNG/TNF RNA transcription activity. Throughout activation, nuclear cytokine mRNAs accumulated, whereas cytoplasmic cytokine mRNA was degraded through translation-dependent decay. Lastly, T-cell smFISH uncovered cytokine-specific regulation by the RNA-binding protein HuR. Thus, T-cell smFISH provides novel insights in the intricate (post)-transcriptional processes in T cells.
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T cells are critical effector cells counteracting infections and malignancies. To achieve this, they produce pro-inflammatory cytokines, including IFN-γ and TNF. Cytokine production is a tightly regulated process, but the relative contribution of transcriptional and post-transcriptional regulation to mRNA expression remains unknown. We optimized single-molecule FISH for primary human T cells (T-cell smFISH) to simultaneously quantify nascent RNA, levels of mature mRNA, and its localization with single-cell resolution. T-cell smFISH uncovered heterogeneous cytokine mRNA levels, with high cytokine producers displaying biallelic IFNG/TNF RNA transcription activity. Throughout activation, nuclear cytokine mRNAs accumulated, whereas cytoplasmic cytokine mRNA was degraded through translation-dependent decay. Lastly, T-cell smFISH uncovered cytokine-specific regulation by the RNA-binding protein HuR. Thus, T-cell smFISH provides novel insights in the intricate (post)-transcriptional processes in T cells.
This introductory programming book offers a hands-on approach to learning Python, designed specifically for students of natural sciences who wish to enter the world of coding. Covering fundamental programming concepts - from variables and data types to functions and loops - the book presents examples and exercises rooted in applications across biology, physics, and mathematics. In addition to Python fundamentals, readers also build good practices of programming and working with computers, such as using the terminal, navigating an integrated development environment, tracking changes with Git, and writing pseudocode. Through hands-on learning, each chapter builds both confidence and competence, guiding students from simple scripts to more complex code. By the end of the book, students will not only understand Python’s core principles but also have the skills and tools to tackle real coding challenges within their scientific disciplines.
...
This introductory programming book offers a hands-on approach to learning Python, designed specifically for students of natural sciences who wish to enter the world of coding. Covering fundamental programming concepts - from variables and data types to functions and loops - the book presents examples and exercises rooted in applications across biology, physics, and mathematics. In addition to Python fundamentals, readers also build good practices of programming and working with computers, such as using the terminal, navigating an integrated development environment, tracking changes with Git, and writing pseudocode. Through hands-on learning, each chapter builds both confidence and competence, guiding students from simple scripts to more complex code. By the end of the book, students will not only understand Python’s core principles but also have the skills and tools to tackle real coding challenges within their scientific disciplines.