Translation Initiation Cell Biology High throughput and Chemical based Approaches 1st Edition by Jon Lorsch ISBN 0123739640 9780123739643 by Jon Lorsch 9780080553481, 9780123739643 instant download after payment.
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ISBN 10: 0123739640
ISBN 13: 9780123739643
Author: Jon Lorsch
Translation Initiation Cell Biology High throughput and Chemical based Approaches 1st Table of contents:
Part I: The Cell Biology of Translation Initiation
Chapter 1: Fundamentals of Eukaryotic Translation Initiation
- Overview of the Central Dogma and Protein Synthesis
- Ribosome Structure and Function (40S, 60S, 80S subunits)
- The mRNA Template: Cap, UTRs, and Coding Sequence
- Key Eukaryotic Initiation Factors (eIFs): Structure and General Function
- The Canonical Pathway: Cap-Dependent Initiation
- eIF4F Complex (eIF4E, eIF4G, eIF4A)
- Ribosome Recruitment (eIF3)
- Scanning and AUG Recognition
- 60S Subunit Joining
- Regulation of Canonical Initiation: Phosphorylation, Availability of eIFs
Chapter 2: Alternative Modes of Translation Initiation
- Internal Ribosome Entry Site (IRES)-Mediated Translation
- Discovery and Characteristics of IRES Elements
- Mechanisms of IRES-Dependent Initiation (eIF-dependent vs. eIF-independent)
- Physiological and Pathological Roles of IRESs (e.g., viral translation, stress response)
- Leaky Scanning and Re-initiation
- Definition and Mechanisms
- Roles in Gene Regulation (e.g., uORFs)
- Non-AUG Initiation
- CUG, GUG, and Other Non-Canonical Start Codons
- Mechanisms and Biological Significance
Chapter 3: Regulation of Translation Initiation in Cellular Processes
- Stress Responses:
- Integrated Stress Response (ISR) and eIF2α Phosphorylation
- mTOR Pathway and eIF4F Regulation (4E-BP, S6K)
- Hypoxia and Nutrient Deprivation
- Cell Cycle Control and Proliferation
- Development and Differentiation
- Neuronal Plasticity and Memory Formation
- Viral Infection: Host Shutoff and Viral Takeover of Translation Machinery
Chapter 4: Pathological Roles of Dysregulated Translation Initiation
- Cancer: Aberrant eIF Expression, mTOR Pathway Activation
- Neurological Disorders: Fragile X Syndrome, Alzheimer's, Parkinson's (e.g., FMRP, eIF2α)
- Metabolic Diseases: Diabetes, Obesity
- Viral Pathogenesis: Exploitation and Evasion Strategies
- Rare Genetic Disorders Linked to eIF Mutations
Part II: High-throughput Approaches to Study Translation Initiation
Chapter 5: Ribosome Profiling (Ribo-seq)
- Principles and Methodology of Ribo-seq
- Polysome Footprinting and Deep Sequencing
- Computational Analysis: P-site Determination, Translation Efficiency
- Applications in Translation Initiation Research:
- Identifying Translation Start Sites (TSS) and Alternative Open Reading Frames (ORFs)
- Mapping Ribosome Movement and Translation Rates
- Investigating Context-Dependent Initiation (e.g., uORFs, non-AUG)
- Advantages and Limitations of Ribo-seq
Chapter 6: Other Omics-based Approaches
- Translational State-Dependent RNA Sequencing (TRAP-seq, RiboTag)
- Mass Spectrometry-Based Proteomics for Quantifying Newly Synthesized Proteins
- Chemical Proteomics for Profiling eIF Interactions and Modifications
- CRISPR-based Screens to Identify Genetic Regulators of Initiation
- Quantitative Imaging Techniques for Visualizing Translation in Live Cells
Chapter 7: Computational and Bioinformatics Tools for Initiation Analysis
- Software and Algorithms for Ribo-seq Data Analysis
- Prediction of IRES Elements and Regulatory Motifs
- Databases of Translation Initiation Sites and Regulatory Elements
- Network Analysis of Translation Regulatory Pathways
Part III: Chemical-based Approaches and Therapeutic Interventions
Chapter 8: Small Molecule Modulators of Translation Initiation
- Inhibitors Targeting Canonical Initiation:
- eIF4A Inhibitors (e.g., Rocaglates, Hippuristanol)
- eIF4E Inhibitors
- eIF2α Kinase Inhibitors
- mTOR Inhibitors (Rapamycin and Analogs)
- Modulators of IRES-Mediated Translation
- Compounds Affecting Ribosome Biogenesis and Function
- Strategies for High-Throughput Screening of Initiation Modulators
Chapter 9: Chemical Biology Tools for Probing Initiation Mechanisms
- Photo-Crosslinking Approaches for Mapping RNA-Protein Interactions (e.g., CLIP-seq variants)
- Chemical Probes for Visualizing Translation Initiation Events
- Bioorthogonal Labeling Strategies for Tracking Nascent Proteins
- Tools for Studying eIF Modifications and Dynamics
Chapter 10: Therapeutic Strategies Targeting Translation Initiation
- Translation Initiation as a Drug Target in Cancer:
- Targeting eIF4F Axis
- Repurposing Existing Drugs
- Antiviral Strategies: Exploiting Differences in Host vs. Viral Translation
- Therapeutic Approaches for Neurological and Metabolic Disorders
- Challenges and Opportunities in Drug Development Targeting Translation Initiation
- Specificity, Off-Target Effects, and Resistance Mechanisms
Chapter 11: Gene Therapy and Nucleic Acid-Based Approaches
- Antisense Oligonucleotides (ASOs) and siRNA for Modulating eIF Expression
- mRNA-based Therapeutics and Their Reliance on Efficient Initiation
- CRISPR/Cas9 for Engineering Regulatory Elements (e.g., uORFs, IRESs)
- Ribozymes and Aptamers as Modulators of Initiation
Conclusion
- Synthesis of Key Discoveries and Emerging Themes
- Bridging the Gap: Integrating Cell Biology, High-throughput, and Chemical Approaches
- Future Directions in Translation Initiation Research:
- Single-Cell Resolution Studies
- In Vivo Imaging of Translation
- AI/Machine Learning in Predicting Regulatory Mechanisms
- Development of Novel Therapeutic Modalities
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